A Phase I, Multicenter Dose Escalation Study in Patients With Hairy Cell Leukemia

Sponsor
MedImmune LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00586924
Collaborator
Cambridge Antibody Technology (Other)
49
4
6
95.9
12.3
0.1

Study Details

Study Description

Brief Summary

A dose-escalation study to identify the dose-limiting toxicity (DLT) and maximum tolerated dose (MTD), defined as the highest dose that can safely be given to a participant and establish the safest dose based on the highest tolerated dose for clinical testing.

Condition or Disease Intervention/Treatment Phase
  • Drug: Moxetumomab Pasudotox (CAT 8015)
  • Drug: Moxetumomab Pasudotox (CAT 8015)
  • Drug: Moxetumomab Pasudotox (CAT 8015)
  • Drug: Moxetumomab Pasudotox (CAT 8015)
  • Drug: CAT 8015 (Moxetumomab Pasudotox)
  • Drug: Moxetumomab Pasudotox (CAT 8015)
Phase 1

Detailed Description

A Phase 1, multicenter, dose escalation study of moxetumomab pasudotox (CAT-8015) in participants with relapsed or refractory hairy cell leukemia (HCL) to estimate the MTD, defined as the highest dose that can be safely administered to a patient, and to establish a safe dose, based on the MTD, for subsequent clinical testing (Phase 2 recommended dose).

Study Design

Study Type:
Interventional
Actual Enrollment :
49 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I, Multicenter, Dose Escalation Study of CAT-8015 in Patients With Relapsed or Refractory Hairy Cell Leukemia (HCL)
Actual Study Start Date :
May 10, 2007
Actual Primary Completion Date :
May 6, 2015
Actual Study Completion Date :
May 6, 2015

Arms and Interventions

Arm Intervention/Treatment
Experimental: 5 mcg/kg

Participants received intravenous infusion of 5 microgram per kilogram (mcg/kg) moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Drug: Moxetumomab Pasudotox (CAT 8015)
Participants received intravenous infusion of 5 microgram per kilogram (mcg/kg) moxetumomab pasudotox (CAT-8015) on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Experimental: 10 mcg/kg

Participants received intravenous infusion of 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Drug: Moxetumomab Pasudotox (CAT 8015)
Participants received intravenous infusion of 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Experimental: 20 mcg/kg

Participants received intravenous infusion of 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Drug: Moxetumomab Pasudotox (CAT 8015)
Participants received intravenous infusion of 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Experimental: 30 mcg/kg

Participants received intravenous infusion of 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Drug: Moxetumomab Pasudotox (CAT 8015)
Participants received intravenous infusion of 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Experimental: 40 mcg/kg

Participants received intravenous infusion of 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Drug: CAT 8015 (Moxetumomab Pasudotox)
Participants received intravenous infusion of 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Experimental: 50 mcg/kg

Participants received intravenous infusion of 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Drug: Moxetumomab Pasudotox (CAT 8015)
Participants received intravenous infusion of 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.

Outcome Measures

Primary Outcome Measures

  1. Number of Participants With Dose Limiting Toxicities (DLTs) [Cycle 1 Day 1 to Cycle 2 Day 10 (each cycle duration was 28 days)]

    Adverse events are suspected of causal relationship to drug and are >=Grade (G) 3 in severity considered DLTs: G 3 or 4 hematologic abnormalities at baseline due to disease were not evaluable for hematologic DLT, G 2 allergic reactions of bronchospasm or urticaria, or any >= G3 allergic reaction, in presence of pre-medication were considered DLTs. Following >= G 3 non-hematological treatment-related toxicities not considered DLTs: Tumor lysis syndrome, G 3 low electrolyte levels with pre-existing low levels of same electrolytes, anticoagulant therapy, G 3 or 4 infection or neutropenic fever unless relationship to IP is suspected, G 3 transaminase, alkaline phosphatase, bilirubin or other liver function test elevation provided resolution to values required for study entry prior to start of next cycle, G 3 fever, G 3 hypertriglyceridemia and hypercholesterolemia, and G 4 hypertriglyceridemia lasting <2 months, G 3 hypoalbuminemia lasting <7 days occurred in absence of CLS.

  2. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs) [From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)]

    The TEAEs are defined as adverse events (AEs) present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox.

  3. Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) [From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)]

    Vital signs abnormalities reported as TEAEs included pyrexia, weight increased, dyspnoea, hypoxia, hypertension, hypotension.

  4. Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs) [From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)]

    Cardiac AEs observed in participants with clinically significant ECG abnormalities included; ECG QT prolonged, Sinus tachycardia and Atrioventricular block first degree.

  5. Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs) [From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)]

    An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event.

  6. Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR) [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Objective response rate defined as proportion of participants with confirmed CR or confirmed PR according to Response Evaluation Criteria for hairy cell leukemia (HCL). A CR is defined as: No evidence of leukemic cells by routine H/E stains of peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as: Neutrophils >= 1,500/mcL, Platelets >= 100,000/mcL, and Hemoglobin >= 11.0 gm/dL without transfusions or growth factors for at least 4 weeks. Partial response requires all of following: >=50% reduction in peripheral blood lymphocyte from pretreatment baseline value, lymphadenopathy, and abnormal hepatosplenomegaly by CT scan or physical exam, and complete blood count as Neutrophils >= 1,500/mcL, Platelets >=100,000/mcL, and Hemoglobin >= 11.0 g/dL or 50% improvement of all parameters over baseline without transfusions or growth factors for at least 4 weeks.

  7. Number of Participants With Complete Response (CR) [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    The CR is defined by: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as exhibited by: Neutrophils >= 1,500/microliter (mcL), Platelets >= 100,000/mcL, and Hemoglobin >= 11.0 gram per deciliter (gm/dL) without transfusions or growth factors for at least 4 weeks.

  8. Number of Participants With Partial Response (PR) [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Partial response requires all of the following: >=50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, >=50% reduction in lymphadenopathy, >=50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam, Neutrophils >= 1,500/mcL or 50% improvement over baseline without growth factors for at least 4 weeks, Platelets >=100,000/mcL or 50% improvement over baseline, and Hemoglobin >= 11.0 g/dL or 50% improvement over baseline without transfusions or growth factors for at least 4 weeks. For participants who are transfusion-dependent at baseline, a hemoglobin of >= 9.0 g/dL without transfusions or growth factors for at least 4 weeks.

  9. Number of Participants With Stable Disease (SD) [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Stable disease was characterized by not meeting the criteria for CR, PR or PD.

  10. Number of Participants With Progressive Disease (PD) [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Progressive disease is defined by at least one of the following compared to pretreatment:>= 25% increase in the sum of the products of the greatest perpendicular dimensions of at least two lymph nodes on two consecutive examinations at least 2 weeks apart (at least 1 node must be >= 2 cm) or appearance of new palpable lymph nodes, >=25% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, or appearance of new palpable hepatomegaly or splenomegaly that was not previously present, >=50% increase in the absolute number of circulating lymphocytes, >=25% decrease in hemoglobin (must be < 11g/dL), platelets (must be < 100,000/mcL), or absolute neutrophil count (must be < 1500/mcL) unless these are judged to be effects of treatment.

  11. Time to Complete Response [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Time to complete response (CR) was measured from the start of moxetumomab pasudotox treatment to the first documentation of CR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved a CR. Time to complete response was summarized using Kaplan-Meier estimates (median time, 95% confidence interval [CI] for median time).

  12. Time to Objective Response [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Time to OR was measured from the start of moxetumomab pasudotox treatment to the first documentation of OR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved an OR (CR or PR). Objective response (OR) was defined as the participants with confirmed CR or confirmed PR according to Response Evaluation Criteria.

  13. Duration of Complete Response [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Duration of CR was measured from the first documentation of CR to the first documented non-CR and was evaluated in participants who had achieved an CR. Duration of CR were summarized using Kaplan-Meier estimates (median time, 95% CI for median time).

  14. Duration of Objective Response [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Duration of response was measured from the first documentation of objective response (OR) to the first documented non-response of SD, PD, or relapse and was only evaluated in participants who had achieved an OR (CR or PR). Duration of OR was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).

  15. Time to Progression [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    Time to disease progression/relapse is measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression or relapse and was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).

  16. Progression-free Survival (PFS) [From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)]

    PFS was measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression/relapse or death, whichever occurred first. PFS was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).

  17. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1 [Cycle 1 Day 1: pre-infusion; at 15 minutes (min) during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 hours (h) post infusion]

    The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.

  18. Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5 [Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.

  19. Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1 [Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.

  20. Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5 [Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.

  21. Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1 [Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  22. Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5 [Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.

  23. Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1 [Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by area under plasma concentration-time curve from time zero to infinite time (AUC[0-infinity]).

  24. Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5 [Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity).

  25. Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1 [Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

  26. Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5 [Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).

  27. AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 [Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The AUC accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of AUC(0-last) on the last day and the first day of a multiple dose regimen: Day 5/Day 1.

  28. Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1 [Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion]

    The Cmax accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of Cmax on the last day and the first day of a multiple dose regimen: Day 5/Day 1.

Secondary Outcome Measures

  1. Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity [Up to end of treatment (approximately 8 years)]

    Participants tested for immunogenicity to moxetumomab pasudotox prior to enrollment, before each cycle and at end of study. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates. Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit >50% of the binding of CAT-8015 to CD22 using an ELISA-based method.

  2. CD22 Expression Levels From Peripheral Blood by Best Response [Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)]

    Participants malignant cells (peripheral blood) were tested for cluster of differentiation 22 (CD22) expression by fluorescence-activated cell sorter (FACS) analysis.

  3. CD22 Expression Levels From Bone Marrow by Best Response [Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)]

    Participants malignant cells (paraffin block biopsy specimen) were tested for CD22 expression by FACS analysis.

  4. Soluble CD22 Levels by Best Response [Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)]

    Soluble CD22 was collected from the participant's plasma and was performed at the NCI using an ELISA method.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 99 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No

Inclusion Criteria: Confirmed diagnosis of HCL, Measurable disease, Participant's must have had at least 2 prior systemic therapies. There must have been at least 2 prior courses of purine analog, or 1 if the response to this course lasted less than (<) 2 years, or if the participant had unacceptable toxicity to purine analog, Eastern Cooperative Oncology Group (ECOG) performance status of 0-2, Participant's with other cancers who meet eligibility criteria and have less than 5 years of disease free survival will be considered on a case-by-case basis, Life expectancy of greater than 6 months, as assessed by principal investigator, Must be able to understand and sign informed consent, Must be at least 18 years old, Female and male participants must agree to use an approved method of contraception during the study.

Exclusion Criteria: - History of allogeneic bone marrow transplant, Documented and ongoing central nervous system involvement with their malignant disease (history of central nervous system (CNS) involvement is not an exclusion criteria), Pregnant or breast-feeding females, HIV positive serology (due to increased risk of severe infection and unknown interaction of CAT-8015 with antiretroviral drugs, Hepatitis B surface antigen positive. - Hepatic function: Serum transaminases (either alanine transaminase (ALT) or aspartate transaminase (AST)) or bilirubin: greater than or equal to (>=) Grade 2, unless bilirubin is due to Gilbert's disease. -Renal function: Serum creatinine clearance less than or equal to (<=) 60 millilitre per minute (mL/min) as estimated by Cockroft-Gault formula. -Hematologic function: The absolute neutrophil count (ANC) < 1000/ cubic millimetres (cmm), or platelet count <50,000/cmm, if these cytopenias are not judged by the investigator to be due to underlying disease (i.e. potentially reversible with anti-neoplastic therapy). -Pulmonary function: Participant's with < 50% of predicted forced expiratory volume (FEV1) or <50% of predicted diffusing capacity for carbon monoxide (DLCO), corrected for hemoglobin concentration and alveolar volume. Uncontrolled pulmonary infection, presence of pulmonary edema, Oxygen saturation at rest < 88% measured by pulse oximetry or partial pressure of oxygen (PaO2) < 55 millimetre(s) of mercury (mm Hg), Serum albumin < 2 g/dL, Radioimmunotherapy within 2 years prior to enrollment in study.

Contacts and Locations

Locations

Site City State Country Postal Code
1 Research Site Stanford California United States 94305
2 Research Site Chicago Illinois United States 60611
3 Research Site Bethesda Maryland United States 20892
4 Research Site Lodz Poland 93-510

Sponsors and Collaborators

  • MedImmune LLC
  • Cambridge Antibody Technology

Investigators

  • Study Director: MedImmune LLC, MedImmune LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00586924
Other Study ID Numbers:
  • CAT-8015-1001
First Posted:
Jan 7, 2008
Last Update Posted:
Apr 2, 2019
Last Verified:
Dec 1, 2018
Keywords provided by MedImmune LLC
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Period Title: Overall Study
STARTED 3 3 3 3 4 33
COMPLETED 0 0 0 0 0 0
NOT COMPLETED 3 3 3 3 4 33

Baseline Characteristics

Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg Total
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Total of all reporting groups
Overall Participants 3 3 3 3 4 33 49
Age (Years) [Mean (Standard Deviation) ]
Years
56.3
(14.2)
54.3
(6.1)
56.3
(3.1)
58.3
(4.0)
61.8
(11.1)
55.8
(9.0)
56.4
(8.7)
Sex: Female, Male (Count of Participants)
Female
1
33.3%
0
0%
0
0%
1
33.3%
1
25%
5
15.2%
8
16.3%
Male
2
66.7%
3
100%
3
100%
2
66.7%
3
75%
28
84.8%
41
83.7%

Outcome Measures

1. Primary Outcome
Title Number of Participants With Dose Limiting Toxicities (DLTs)
Description Adverse events are suspected of causal relationship to drug and are >=Grade (G) 3 in severity considered DLTs: G 3 or 4 hematologic abnormalities at baseline due to disease were not evaluable for hematologic DLT, G 2 allergic reactions of bronchospasm or urticaria, or any >= G3 allergic reaction, in presence of pre-medication were considered DLTs. Following >= G 3 non-hematological treatment-related toxicities not considered DLTs: Tumor lysis syndrome, G 3 low electrolyte levels with pre-existing low levels of same electrolytes, anticoagulant therapy, G 3 or 4 infection or neutropenic fever unless relationship to IP is suspected, G 3 transaminase, alkaline phosphatase, bilirubin or other liver function test elevation provided resolution to values required for study entry prior to start of next cycle, G 3 fever, G 3 hypertriglyceridemia and hypercholesterolemia, and G 4 hypertriglyceridemia lasting <2 months, G 3 hypoalbuminemia lasting <7 days occurred in absence of CLS.
Time Frame Cycle 1 Day 1 to Cycle 2 Day 10 (each cycle duration was 28 days)

Outcome Measure Data

Analysis Population Description
Evaluable population for DLT included all participants who received any treatment of moxetumomab pasudotox, completed at least Cycle 2 Day 10, or discontinued treatment due to a DLT on or before Cycle 2 Day 10.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 3 3
Count of Participants [Participants]
0
0%
0
0%
0
0%
0
0%
0
0%
0
0%
2. Primary Outcome
Title Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Treatment Emergent Serious Adverse Events (TESAEs)
Description The TEAEs are defined as adverse events (AEs) present at baseline that worsened in intensity after administration of investigational product or events absent at baseline that emerged after administration of study drug, for the period extending to 30 days after the last dose of study drug. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening situation (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect in the offspring of a participant who received moxetumomab pasudotox.
Time Frame From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
TEAEs
3
100%
3
100%
3
100%
3
100%
4
100%
33
100%
TESAEs
0
0%
0
0%
0
0%
2
66.7%
0
0%
4
12.1%
3. Primary Outcome
Title Number of Participants With Vital Signs Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description Vital signs abnormalities reported as TEAEs included pyrexia, weight increased, dyspnoea, hypoxia, hypertension, hypotension.
Time Frame From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Pyrexia
1
33.3%
1
33.3%
2
66.7%
3
100%
1
25%
16
48.5%
Weight increased
1
33.3%
0
0%
0
0%
0
0%
0
0%
6
18.2%
Dyspnoea
1
33.3%
0
0%
0
0%
1
33.3%
0
0%
6
18.2%
Hypoxia
0
0%
0
0%
0
0%
1
33.3%
0
0%
1
3%
Hypertension
0
0%
1
33.3%
0
0%
1
33.3%
0
0%
0
0%
Hypotension
0
0%
0
0%
0
0%
2
66.7%
0
0%
10
30.3%
4. Primary Outcome
Title Number of Participants With Clinically Relevant Electrocardiogram (ECG) Abnormalities Recorded as Adverse Events (AEs)
Description Cardiac AEs observed in participants with clinically significant ECG abnormalities included; ECG QT prolonged, Sinus tachycardia and Atrioventricular block first degree.
Time Frame From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
ECG QT prolonged
1
33.3%
0
0%
0
0%
2
66.7%
0
0%
2
6.1%
Sinus tachycardia
0
0%
0
0%
0
0%
1
33.3%
0
0%
2
6.1%
Atrioventricular block first degree
0
0%
0
0%
0
0%
0
0%
1
25%
0
0%
5. Primary Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities Recorded as Treatment-Emergent Adverse Events (TEAEs)
Description An abnormal laboratory finding which required an action or intervention by the investigator, or a finding judged by the investigator to represent a change beyond the range of normal physiologic fluctuation were reported as an adverse event.
Time Frame From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Alanine aminotransferase increased
1
33.3%
1
33.3%
1
33.3%
3
100%
2
50%
25
75.8%
Aspartate aminotransferase increased
2
66.7%
1
33.3%
1
33.3%
2
66.7%
1
25%
24
72.7%
Blood alkaline phosphatase increased
0
0%
0
0%
0
0%
1
33.3%
0
0%
5
15.2%
Blood bicarbonate decreased
0
0%
0
0%
0
0%
0
0%
0
0%
5
15.2%
Blood bilirubin increased
2
66.7%
1
33.3%
1
33.3%
0
0%
1
25%
2
6.1%
Blood creatine phosphokinase increased
0
0%
1
33.3%
0
0%
1
33.3%
0
0%
4
12.1%
Blood creatinine increased
1
33.3%
0
0%
0
0%
1
33.3%
0
0%
11
33.3%
Blood triglycerides increased
0
0%
1
33.3%
0
0%
1
33.3%
1
25%
2
6.1%
Gamma-glutamyltransferase increased
0
0%
0
0%
0
0%
1
33.3%
0
0%
7
21.2%
Blood uric acid increased
1
33.3%
0
0%
0
0%
1
33.3%
0
0%
1
3%
Hyperglycaemia
2
66.7%
0
0%
0
0%
2
66.7%
2
50%
13
39.4%
Hypermagnesaemia
0
0%
0
0%
0
0%
0
0%
1
25%
12
36.4%
Hypernatraemia
0
0%
0
0%
0
0%
0
0%
0
0%
6
18.2%
Hypertriglyceridaemia
0
0%
0
0%
1
33.3%
0
0%
0
0%
19
57.6%
Hyperuricaemia
0
0%
0
0%
0
0%
0
0%
0
0%
4
12.1%
Hypoalbuminaemia
2
66.7%
1
33.3%
1
33.3%
3
100%
3
75%
25
75.8%
Hypocalcaemia
0
0%
0
0%
0
0%
1
33.3%
1
25%
11
33.3%
Hypoglycaemia
1
33.3%
1
33.3%
0
0%
0
0%
1
25%
1
3%
Hypokalaemia
0
0%
0
0%
0
0%
2
66.7%
0
0%
2
6.1%
Hypomagnesaemia
0
0%
0
0%
1
33.3%
1
33.3%
1
25%
7
21.2%
Hyponatraemia
0
0%
0
0%
0
0%
2
66.7%
3
75%
7
21.2%
Hypophosphataemia
0
0%
0
0%
0
0%
1
33.3%
0
0%
10
30.3%
Hemoglobin urine
0
0%
0
0%
0
0%
1
33.3%
0
0%
0
0%
Protein urine
0
0%
0
0%
0
0%
0
0%
1
25%
1
3%
Proteinuria
0
0%
0
0%
0
0%
0
0%
0
0%
9
27.3%
Hemoglobinuria
0
0%
0
0%
0
0%
0
0%
0
0%
3
9.1%
Hypercholesterolaemia
0
0%
0
0%
0
0%
0
0%
0
0%
9
27.3%
Hyperkalaemia
0
0%
1
33.3%
0
0%
0
0%
1
25%
5
15.2%
Lymphopenia
2
66.7%
0
0%
2
66.7%
0
0%
0
0%
25
75.8%
White blood cell count decresed
2
66.7%
1
33.3%
2
66.7%
1
33.3%
2
50%
17
51.5%
Lymphocyte count decreased
0
0%
1
33.3%
1
33.3%
2
66.7%
2
50%
5
15.2%
Neutrophil count decreased
2
66.7%
0
0%
0
0%
0
0%
0
0%
10
30.3%
Hemoglobin decreased
2
66.7%
0
0%
2
66.7%
1
33.3%
1
25%
9
27.3%
Platelet count decreased
1
33.3%
0
0%
0
0%
0
0%
2
50%
6
18.2%
Haptoglobin decreased
0
0%
0
0%
0
0%
1
33.3%
1
25%
7
21.2%
6. Primary Outcome
Title Number of Participants With Objective Response Rate (ORR): Complete Response (CR) or Partial Response (PR)
Description Objective response rate defined as proportion of participants with confirmed CR or confirmed PR according to Response Evaluation Criteria for hairy cell leukemia (HCL). A CR is defined as: No evidence of leukemic cells by routine H/E stains of peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as: Neutrophils >= 1,500/mcL, Platelets >= 100,000/mcL, and Hemoglobin >= 11.0 gm/dL without transfusions or growth factors for at least 4 weeks. Partial response requires all of following: >=50% reduction in peripheral blood lymphocyte from pretreatment baseline value, lymphadenopathy, and abnormal hepatosplenomegaly by CT scan or physical exam, and complete blood count as Neutrophils >= 1,500/mcL, Platelets >=100,000/mcL, and Hemoglobin >= 11.0 g/dL or 50% improvement of all parameters over baseline without transfusions or growth factors for at least 4 weeks.
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Count of Participants [Participants]
3
100%
3
100%
2
66.7%
2
66.7%
3
75%
29
87.9%
7. Primary Outcome
Title Number of Participants With Complete Response (CR)
Description The CR is defined by: No evidence of leukemic cells by routine H/E stains of the peripheral blood and bone marrow. No hepatomegaly, splenomegaly, or lymphadenopathy by physical examination and/or appropriate radiographic techniques. Normal complete blood count as exhibited by: Neutrophils >= 1,500/microliter (mcL), Platelets >= 100,000/mcL, and Hemoglobin >= 11.0 gram per deciliter (gm/dL) without transfusions or growth factors for at least 4 weeks.
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Count of Participants [Participants]
0
0%
2
66.7%
2
66.7%
1
33.3%
2
50%
21
63.6%
8. Primary Outcome
Title Number of Participants With Partial Response (PR)
Description Partial response requires all of the following: >=50% decrease in peripheral blood lymphocyte count from the pretreatment baseline value, >=50% reduction in lymphadenopathy, >=50% reduction in abnormal hepatosplenomegaly by computed tomography or physical exam, Neutrophils >= 1,500/mcL or 50% improvement over baseline without growth factors for at least 4 weeks, Platelets >=100,000/mcL or 50% improvement over baseline, and Hemoglobin >= 11.0 g/dL or 50% improvement over baseline without transfusions or growth factors for at least 4 weeks. For participants who are transfusion-dependent at baseline, a hemoglobin of >= 9.0 g/dL without transfusions or growth factors for at least 4 weeks.
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Count of Participants [Participants]
3
100%
1
33.3%
0
0%
1
33.3%
1
25%
8
24.2%
9. Primary Outcome
Title Number of Participants With Stable Disease (SD)
Description Stable disease was characterized by not meeting the criteria for CR, PR or PD.
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Count of Participants [Participants]
0
0%
0
0%
1
33.3%
1
33.3%
0
0%
4
12.1%
10. Primary Outcome
Title Number of Participants With Progressive Disease (PD)
Description Progressive disease is defined by at least one of the following compared to pretreatment:>= 25% increase in the sum of the products of the greatest perpendicular dimensions of at least two lymph nodes on two consecutive examinations at least 2 weeks apart (at least 1 node must be >= 2 cm) or appearance of new palpable lymph nodes, >=25% increase in the size of the liver and/or spleen as determined by measurement below the respective costal margin, or appearance of new palpable hepatomegaly or splenomegaly that was not previously present, >=50% increase in the absolute number of circulating lymphocytes, >=25% decrease in hemoglobin (must be < 11g/dL), platelets (must be < 100,000/mcL), or absolute neutrophil count (must be < 1500/mcL) unless these are judged to be effects of treatment.
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Count of Participants [Participants]
0
0%
0
0%
0
0%
0
0%
1
25%
0
0%
11. Primary Outcome
Title Time to Complete Response
Description Time to complete response (CR) was measured from the start of moxetumomab pasudotox treatment to the first documentation of CR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved a CR. Time to complete response was summarized using Kaplan-Meier estimates (median time, 95% confidence interval [CI] for median time).
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox. The "Overall Number of Participants Analyzed" denotes the number of participants who had achieved a CR.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 0 2 2 1 2 21
Median (95% Confidence Interval) [months]
2.53
9.56
3.71
2.53
3.94
12. Primary Outcome
Title Time to Objective Response
Description Time to OR was measured from the start of moxetumomab pasudotox treatment to the first documentation of OR and was evaluated only in participants who received any treatment of moxetumomab pasudotox and had achieved an OR (CR or PR). Objective response (OR) was defined as the participants with confirmed CR or confirmed PR according to Response Evaluation Criteria.
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox. The "Overall Number of Participants Analyzed" denotes the number of participants who had achieved an OR (CR or PR).
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 2 2 3 29
Median (95% Confidence Interval) [months]
3.02
1.12
8.2
8.18
1.08
1.05
13. Primary Outcome
Title Duration of Complete Response
Description Duration of CR was measured from the first documentation of CR to the first documented non-CR and was evaluated in participants who had achieved an CR. Duration of CR were summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox. Here, the "Overall Number of Participants Analyzed" denotes the number of participants who had achieved CR and had the first documented non-CR till end of the study.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 0 1 1 1 0 9
Median (95% Confidence Interval) [months]
NA
25.89
70.34
42.35
14. Primary Outcome
Title Duration of Objective Response
Description Duration of response was measured from the first documentation of objective response (OR) to the first documented non-response of SD, PD, or relapse and was only evaluated in participants who had achieved an OR (CR or PR). Duration of OR was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox. Here, the "Overall Number of Participants Analyzed" denotes the number of participants who had achieved an OR (CR or PR) and had the first documented non-response of SD, PD, or relapse.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 1 1 1 1 0 6
Median (95% Confidence Interval) [months]
8.34
84.44
80.95
78.29
NA
15. Primary Outcome
Title Time to Progression
Description Time to disease progression/relapse is measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression or relapse and was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Median (95% Confidence Interval) [months]
11.33
NA
NA
82.07
NA
NA
16. Primary Outcome
Title Progression-free Survival (PFS)
Description PFS was measured from the start of moxetumomab pasudotox treatment until the first documentation of disease progression/relapse or death, whichever occurred first. PFS was summarized using Kaplan-Meier estimates (median time, 95% CI for median time).
Time Frame From Baseline (predose of Cycle 1 Day 1) through end of study (until CR, PD, initiation of alternative therapy, unacceptable toxicity, development of neutralizing antibodies, or other study discontinuation reasons) (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Median (95% Confidence Interval) [months]
11.33
NA
NA
82.07
NA
NA
17. Primary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 1
Description The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.
Time Frame Cycle 1 Day 1: pre-infusion; at 15 minutes (min) during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 hours (h) post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 3 2 2 4 11
Median (Full Range) [hours]
0.508
0.467
0.367
0.467
0.267
0.417
18. Primary Outcome
Title Time to Reach Maximum Observed Plasma Concentration (Tmax) of Moxetumomab Pasudotox for Cycle 1 on Day 5
Description The Tmax is the time to reach maximum observed plasma concentration of Moxetumomab Pasudotox.
Time Frame Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 2 4 12
Median (Full Range) [hours]
0.500
0.467
0.250
0.517
0.475
0.417
19. Primary Outcome
Title Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 1
Description The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.
Time Frame Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 2 4 12
Mean (Standard Deviation) [nanogram per milliliter (ng/mL)]
77.5
(70.0)
86.3
(41.9)
49.4
(46.3)
443
(NA)
290
(107)
435
(260)
20. Primary Outcome
Title Maximum Observed Serum Concentration (Cmax) for Moxetumomab Pasudotox for Cycle 1 on Day 5
Description The Cmax is the maximum observed plasma concentration of Moxetumomab Pasudotox.
Time Frame Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 12
Mean (Standard Deviation) [ng/mL]
103
(40.5)
135
(49.1)
161
(136)
420
(384)
701
(328)
738
(316)
21. Primary Outcome
Title Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 1
Description The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time Frame Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 3 2 2 4 11
Mean (Standard Deviation) [nanogram*hour per milliliter (ng*h/mL)]
113
(NA)
31.0
(20.9)
109
(NA)
897
(NA)
183
(146)
558
(590)
22. Primary Outcome
Title Area Under the Curve From Time Zero to the Time of Last Quantifiable Concentration (AUC[0-last]) of Moxetumomab Pasudotox for Cycle 1 on Day 5
Description The AUC (0-last) is the area under the plasma concentration-time curve from time zero to last quantifiable time.
Time Frame Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 2 4 12
Mean (Standard Deviation) [ng*h/mL]
179
(155)
90.2
(52.3)
93.2
(113)
1360
(NA)
1640
(1270)
1920
(1290)
23. Primary Outcome
Title Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 1
Description Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by area under plasma concentration-time curve from time zero to infinite time (AUC[0-infinity]).
Time Frame Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 0 1 2 1 8
Mean (Standard Deviation) [Milliliter/kilogram/hour (mL/kg/h)]
32.6
(NA)
49.1
(NA)
43.9
(NA)
91.8
(NA)
106
(80.2)
24. Primary Outcome
Title Systemic Clearance (CL) of Moxetumomab Pasudotox for Cycle 1 on Day 5
Description Systemic Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. The total systemic clearance after intravenous dose was estimated by dividing the total administered dose by AUC(0-infinity).
Time Frame Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 2 1 2 4 10
Mean (Standard Deviation) [mL/kg/h]
13.3
(NA)
68.9
(NA)
66.3
(NA)
18.7
(NA)
45.5
(47.6)
33.3
(37.5)
25. Primary Outcome
Title Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 1
Description The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time Frame Cycle 1 Day 1: pre-infusion; at 15 min during the infusion; at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 0 1 2 1 8
Mean (Standard Deviation) [hours]
0.643
(NA)
3.77
(NA)
1.00
(NA)
0.375
(NA)
0.799
(0.755)
26. Primary Outcome
Title Terminal Phase Elimination Half Life (t1/2) of Moxetumomab Pasudotox for Cycle 1 on Day 5
Description The elimination half-life (t1/2) is the time measured for the plasma concentration to decrease by 1 half to its original concentration. It is associated with the terminal slope of the semi logarithmic drug concentration-time curve, and is calculated as 0.693/lambda(z).
Time Frame Cycle 1 Day 5: pre infusion; at 15 min during the infusion, at the end of infusion (approximately 5-7 minutes before the end of infusion); and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 2 1 2 4 10
Mean (Standard Deviation) [hours]
2.20
(NA)
0.369
(NA)
0.404
(NA)
1.86
(NA)
1.66
(0.928)
2.06
(0.980)
27. Primary Outcome
Title AUC Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1
Description The AUC accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of AUC(0-last) on the last day and the first day of a multiple dose regimen: Day 5/Day 1.
Time Frame Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 3 2 2 4 11
Median (Full Range) [ratio]
2.62
3.08
3.09
1.93
12.4
3.63
28. Primary Outcome
Title Cmax Accumulation Ratio of Moxetumomab Pasudotox for Cycle 1
Description The Cmax accumulation ratio of moxetumomab pasudotox was calculated as the geometric mean ratio of Cmax on the last day and the first day of a multiple dose regimen: Day 5/Day 1.
Time Frame Cycle 1 Day 1 and Day 5: pre-infusion, at 15 min during the infusion, at the end of infusion, and at 1, 1.5, 2, 4, 8, and 12 h post infusion

Outcome Measure Data

Analysis Population Description
The PK Population consisted of all participants who received any amount of moxetumomab pasudotox and had a sufficient number of serum concentration measurements for computing PK parameters. The "Overall Number of Participants Analyzed" denotes the number of participants evaluated for this outcome measure.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 2 3 2 2 4 11
Median (Full Range) [ratio]
1.11
1.73
2.12
1.48
2.51
1.58
29. Secondary Outcome
Title Number of Participants With Positive Neutralizing Antibodies and Correlation to Antitumor Activity
Description Participants tested for immunogenicity to moxetumomab pasudotox prior to enrollment, before each cycle and at end of study. The neutralization assay measures the capacity of participant's plasma (antibodies) to inhibit the binding of moxetumomab pasudotox to its target, cluster of differentiation 22 (CD22), coated onto enzyme linked immunosorbent assay (ELISA) plates. Significant level of neutralizing antibody activity defined as the capacity of test plasma to inhibit >50% of the binding of CAT-8015 to CD22 using an ELISA-based method.
Time Frame Up to end of treatment (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Count of Participants [Participants]
2
66.7%
2
66.7%
2
66.7%
1
33.3%
0
0%
7
21.2%
30. Secondary Outcome
Title CD22 Expression Levels From Peripheral Blood by Best Response
Description Participants malignant cells (peripheral blood) were tested for cluster of differentiation 22 (CD22) expression by fluorescence-activated cell sorter (FACS) analysis.
Time Frame Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Peripheral Blood: Complete Response
65434.0
(NA)
72632.0
(12010.9)
43803.0
(NA)
61773.0
(NA)
68141.3
(13614.0)
Peripheral Blood: Partial Response
38402.7
(14131.9)
78356.0
(NA)
76264.0
(NA)
52495.0
(NA)
33259.9
(25479.5)
Peripheral Blood: Stable Disease
38939.0
(NA)
84157.0
(NA)
46089.3
(9644.6)
Peripheral Blood: ProgressiveDisease
24645.0
(NA)
31. Secondary Outcome
Title CD22 Expression Levels From Bone Marrow by Best Response
Description Participants malignant cells (paraffin block biopsy specimen) were tested for CD22 expression by FACS analysis.
Time Frame Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Bone Marrow: Complete Response
75157.0
(NA)
50190.0
(NA)
55850.5
(18482.2)
Bone Marrow: Partial Response
36286.0
(NA)
37732.5
(9918.6)
Bone Marrow: Stable Disease
80400.0
(NA)
36767.5
(720.5)
32. Secondary Outcome
Title Soluble CD22 Levels by Best Response
Description Soluble CD22 was collected from the participant's plasma and was performed at the NCI using an ELISA method.
Time Frame Prior to enrollment during screening, and for participants still having malignant cells, the test was to be repeated prior to each cycle of therapy, at the end of treatment, and end of the study (approximately 8 years)

Outcome Measure Data

Analysis Population Description
Safety population included all participants who received any treatment of moxetumomab pasudotox.
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
Measure Participants 3 3 3 3 4 33
Complete Response
2583.0
(NA)
60021.0
(NA)
5109.0
(NA)
10232.0
(NA)
22202.9
(27809.4)
Partial Response
3016.3
(1821.3)
16675.0
(NA)
5122.0
(NA)
18238.5
(45.5)
39493.5
(31216.9)
Stable Disease
184750.0
(21566.8)
528000.0
(NA)
134129.5
(150498.4)
Progressive Disease
7484.0
(NA)

Adverse Events

Time Frame From start of study drug administration until 30 days after the last dose of study drug (approximately 8 years)
Adverse Event Reporting Description
Arm/Group Title 5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Arm/Group Description Participants received IV 5 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued until complete response (CR), progressive disease (PD), initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 10 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 20 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 30 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 40 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy. Participants received IV 50 mcg/kg moxetumomab pasudotox on Days 1, 3, and 5 of every 28-day cycle and continued cycles of therapy until CR, PD, initiation of alternative anticancer therapy, unacceptable toxicity, development of neutralizing antibodies, or another reason to discontinue therapy.
All Cause Mortality
5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total / (NaN) / (NaN) / (NaN) / (NaN) / (NaN) / (NaN)
Serious Adverse Events
5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 0/3 (0%) 0/3 (0%) 0/3 (0%) 2/3 (66.7%) 0/4 (0%) 4/33 (12.1%)
Blood and lymphatic system disorders
Febrile neutropenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/33 (6.1%) 2
Haemolytic uraemic syndrome 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 1/33 (3%) 1
General disorders
Pyrexia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/33 (3%) 1
Infections and infestations
Pneumonia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/33 (3%) 1
Investigations
Blood creatinine increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/33 (3%) 1
Respiratory, thoracic and mediastinal disorders
Bronchospasm 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 0/33 (0%) 0
Dyspnoea 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/33 (3%) 1
Hypoxia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 0/33 (0%) 0
Pulmonary embolism 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/33 (3%) 1
Other (Not Including Serious) Adverse Events
5 mcg/kg 10 mcg/kg 20 mcg/kg 30 mcg/kg 40 mcg/kg 50 mcg/kg
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 3/3 (100%) 3/3 (100%) 3/3 (100%) 3/3 (100%) 4/4 (100%) 33/33 (100%)
Blood and lymphatic system disorders
Febrile neutropenia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/33 (6.1%) 2
Lymphopenia 2/3 (66.7%) 4 0/3 (0%) 0 2/3 (66.7%) 3 0/3 (0%) 0 0/4 (0%) 0 25/33 (75.8%) 62
Cardiac disorders
Sinus tachycardia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 0/4 (0%) 0 2/33 (6.1%) 2
Endocrine disorders
Hypothyroidism 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 3
Gastrointestinal disorders
Abdominal pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 4/33 (12.1%) 7
Constipation 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 2/3 (66.7%) 2 0/4 (0%) 0 5/33 (15.2%) 6
Diarrhoea 1/3 (33.3%) 6 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 5/33 (15.2%) 5
Dyspepsia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 3
Nausea 1/3 (33.3%) 3 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 2 2/4 (50%) 3 13/33 (39.4%) 21
Vomiting 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 3/33 (9.1%) 5
General disorders
Chills 1/3 (33.3%) 2 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 10/33 (30.3%) 17
Fatigue 1/3 (33.3%) 3 1/3 (33.3%) 1 1/3 (33.3%) 1 3/3 (100%) 3 0/4 (0%) 0 8/33 (24.2%) 10
Oedema 1/3 (33.3%) 3 1/3 (33.3%) 2 0/3 (0%) 0 1/3 (33.3%) 1 2/4 (50%) 3 8/33 (24.2%) 10
Oedema peripheral 1/3 (33.3%) 5 1/3 (33.3%) 1 1/3 (33.3%) 1 3/3 (100%) 8 3/4 (75%) 7 13/33 (39.4%) 22
Pyrexia 1/3 (33.3%) 1 1/3 (33.3%) 1 2/3 (66.7%) 4 3/3 (100%) 5 1/4 (25%) 1 15/33 (45.5%) 25
Thrombosis in device 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 4/33 (12.1%) 4
Infections and infestations
Rhinitis 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/4 (0%) 0 7/33 (21.2%) 8
Sinusitis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 2/33 (6.1%) 2
Urinary tract infection 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 2/33 (6.1%) 2
Investigations
Alanine aminotransferase increased 1/3 (33.3%) 2 1/3 (33.3%) 2 1/3 (33.3%) 3 3/3 (100%) 5 2/4 (50%) 5 25/33 (75.8%) 72
Aspartate aminotransferase increased 2/3 (66.7%) 7 1/3 (33.3%) 1 1/3 (33.3%) 3 2/3 (66.7%) 4 1/4 (25%) 4 24/33 (72.7%) 63
Blood alkaline phosphatase increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 5/33 (15.2%) 10
Blood bicarbonate decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 5/33 (15.2%) 5
Blood bilirubin increased 2/3 (66.7%) 4 1/3 (33.3%) 1 1/3 (33.3%) 2 0/3 (0%) 0 1/4 (25%) 1 2/33 (6.1%) 2
Blood creatine phosphokinase increased 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 4/33 (12.1%) 5
Blood creatinine increased 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 3 0/4 (0%) 0 10/33 (30.3%) 19
Blood triglycerides increased 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 2 1/4 (25%) 2 2/33 (6.1%) 2
Blood uric acid increased 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 1/33 (3%) 1
Electrocardiogram qt prolonged 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/4 (0%) 0 2/33 (6.1%) 3
Gamma-glutamyltransferase increased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 7/33 (21.2%) 11
Haemoglobin decreased 2/3 (66.7%) 3 0/3 (0%) 0 2/3 (66.7%) 4 1/3 (33.3%) 1 1/4 (25%) 1 9/33 (27.3%) 15
Haptoglobin decreased 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 1 7/33 (21.2%) 8
Lymphocyte count decreased 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 2 2/3 (66.7%) 3 2/4 (50%) 7 5/33 (15.2%) 9
Neutrophil count decreased 2/3 (66.7%) 2 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 10/33 (30.3%) 14
Platelet count decreased 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/4 (50%) 2 6/33 (18.2%) 9
Weight increased 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 6/33 (18.2%) 7
White blood cell count decreased 2/3 (66.7%) 2 1/3 (33.3%) 1 2/3 (66.7%) 4 1/3 (33.3%) 3 2/4 (50%) 2 17/33 (51.5%) 23
Metabolism and nutrition disorders
Decreased appetite 1/3 (33.3%) 3 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 2/33 (6.1%) 2
Hypercholesterolaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 9/33 (27.3%) 10
Hyperglycaemia 2/3 (66.7%) 5 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 4 2/4 (50%) 2 13/33 (39.4%) 22
Hyperkalaemia 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 5/33 (15.2%) 6
Hypermagnesaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 12/33 (36.4%) 20
Hypernatraemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 6/33 (18.2%) 7
Hypertriglyceridaemia 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 19/33 (57.6%) 31
Hyperuricaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 4/33 (12.1%) 7
Hypoalbuminaemia 2/3 (66.7%) 7 1/3 (33.3%) 1 1/3 (33.3%) 2 3/3 (100%) 9 3/4 (75%) 9 25/33 (75.8%) 72
Hypocalcaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 1 11/33 (33.3%) 18
Hypoglycaemia 1/3 (33.3%) 4 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 1/33 (3%) 1
Hypokalaemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 2 0/4 (0%) 0 2/33 (6.1%) 3
Hypomagnesaemia 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 1/4 (25%) 1 7/33 (21.2%) 15
Hyponatraemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 5 3/4 (75%) 4 7/33 (21.2%) 10
Hypophosphataemia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 10/33 (30.3%) 16
Musculoskeletal and connective tissue disorders
Arthralgia 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 6/33 (18.2%) 8
Back pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 4/33 (12.1%) 4
Bone pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 2 1/4 (25%) 2 1/33 (3%) 2
Musculoskeletal chest pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 3
Myalgia 1/3 (33.3%) 3 2/3 (66.7%) 3 0/3 (0%) 0 3/3 (100%) 7 2/4 (50%) 3 20/33 (60.6%) 36
Neck pain 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 5
Pain in extremity 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 5/33 (15.2%) 5
Nervous system disorders
Dizziness 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 1/4 (25%) 1 8/33 (24.2%) 10
Headache 1/3 (33.3%) 3 1/3 (33.3%) 1 1/3 (33.3%) 4 2/3 (66.7%) 3 1/4 (25%) 7 13/33 (39.4%) 21
Psychiatric disorders
Anxiety 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 1 0/33 (0%) 0
Insomnia 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 4/33 (12.1%) 5
Renal and urinary disorders
Haemoglobinuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 3
Haemorrhage urinary tract 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/4 (25%) 1 8/33 (24.2%) 9
Proteinuria 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 9/33 (27.3%) 13
Respiratory, thoracic and mediastinal disorders
Cough 1/3 (33.3%) 1 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/4 (0%) 0 6/33 (18.2%) 6
Dyspnoea 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 5/33 (15.2%) 5
Epistaxis 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 3
Oropharyngeal pain 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/4 (0%) 0 4/33 (12.1%) 5
Pleural effusion 1/3 (33.3%) 2 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 0/4 (0%) 0 1/33 (3%) 1
Skin and subcutaneous tissue disorders
Hyperhidrosis 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 3/33 (9.1%) 3
Pruritus 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 3/33 (9.1%) 4
Rash 0/3 (0%) 0 1/3 (33.3%) 1 1/3 (33.3%) 1 0/3 (0%) 0 0/4 (0%) 0 8/33 (24.2%) 10
Vascular disorders
Capillary leak syndrome 1/3 (33.3%) 1 0/3 (0%) 0 0/3 (0%) 0 1/3 (33.3%) 1 0/4 (0%) 0 7/33 (21.2%) 8
Hypotension 0/3 (0%) 0 0/3 (0%) 0 0/3 (0%) 0 2/3 (66.7%) 3 0/4 (0%) 0 10/33 (30.3%) 16

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

MedImmune has 60 days to review results communications prior to public release and may delete information that compromises ongoing studies or is considered proprietary. This restriction is not intended to compromise the objective scientific integrity of the manuscript, it being understood that results shall be published regardless of outcome.

Results Point of Contact

Name/Title Nai Shun Yao, MD
Organization MedImmune, LLC
Phone 1-301-398-5936
Email information.center@astrazenea.com
Responsible Party:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00586924
Other Study ID Numbers:
  • CAT-8015-1001
First Posted:
Jan 7, 2008
Last Update Posted:
Apr 2, 2019
Last Verified:
Dec 1, 2018