Inotuzumab Ozogamicin in Treating Younger Patients With B-Lymphoblastic Lymphoma or Relapsed or Refractory CD22 Positive B Acute Lymphoblastic Leukemia

Sponsor
Children's Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02981628
Collaborator
National Cancer Institute (NCI) (NIH)
87
150
2
66.9
0.6
0

Study Details

Study Description

Brief Summary

This phase II trial studies how well inotuzumab ozogamicin works in treating younger patients with B-lymphoblastic lymphoma or CD22 positive B acute lymphoblastic leukemia that has come back (relapsed) or does not respond to treatment (refractory). Inotuzumab ozogamicin is a monoclonal antibody, called inotuzumab, linked to a toxic agent called ozogamicin. Inotuzumab attaches to CD22 positive cancer cells in a targeted way and delivers ozogamicin to kill them.

Detailed Description

PRIMARY OBJECTIVE:
  1. To determine the morphologic response rate (complete response [CR] + complete response with incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin in children with relapsed or refractory CD22+ B acute lymphoblastic leukemia (B-ALL). (Cohort 1)
SECONDARY OBJECTIVES:
  1. To determine the CR/CRi rate following 2 cycles of inotuzumab ozogamicin therapy. (Cohort
    1. To determine the safety of single agent inotuzumab ozogamicin administered at the adult recommended phase 2 dose (RP2D) to pediatric patients with relapsed or refractory CD22+ B-ALL. (Cohort 1) III. To determine the level of minimal residual disease (MRD) by flow cytometry in responding patients. (Cohorts 1 and 2) IV. To determine the incidence, severity, and outcomes of sinusoidal obstruction syndrome (SOS) of the liver in patients during inotuzumab ozogamicin therapy and following subsequent treatment, including myeloablative hematopoietic stem cell transplantation (HSCT). (Cohorts 1 and 2) V. To estimate the 3-year event-free survival (EFS), 3-year overall survival (OS), and among responders, duration of CR/CRi for pediatric patients with relapsed or refractory B-ALL treated with inotuzumab ozogamicin. (Cohort 1) VI. To describe inotuzumab ozogamicin pharmacokinetics and immunogenicity in pediatric patients in the presence of overt leukemia and in remission. (Cohort 1) VII. To determine the safe and tolerable dose of inotuzumab ozogamicin in combination with the augmented modified Berlin-Frankfurt-Munster (mBFM) consolidation chemotherapy backbone. (Cohort 2)
EXPLORATORY OBJECTIVES:
  1. To describe the levels of leukemic blast CD22 surface expression and site density, and to explore the correlation with cytogenetics and clinical outcomes after treatment with inotuzumab ozogamicin. (Cohorts 1 and 2) II. To explore potential mechanisms of resistance to inotuzumab ozogamicin therapy including CD22 splice variants and intracellular signaling pathways. (Cohorts 1 and 2) III. To explore the impact of inotuzumab ozogamicin on humoral immune function and peripheral B cell populations. (Cohorts 1 and 2) IV. To describe the level of MRD by next-generation high-throughput sequencing (HTS) techniques which may detect low level leukemic blast populations that have altered CD22 expression. (Cohorts 1 and 2) V. To prospectively explore candidate SOS biomarkers including the endothelial marker of inflammation Angiopoietin 2 (Ang2) and the hepatic specific complement marker L-ficolin. (Cohorts 1 and 2) VI. To explore the use of prophylactic ursodeoxycholic acid (UDCA) to prevent hepatic damage and SOS during inotuzumab ozogamicin therapy and subsequent HSCT. (Cohorts 1 and 2) VII. To describe the interaction between inotuzumab ozogamicin and chimeric antigen receptor (CAR) T cell therapy before or after treatment with inotuzumab ozogamicin. (Cohorts 1 and 2) VIII. To estimate the CR/CRi rate following one cycle of inotuzumab ozogamicin plus augmented mBFM consolidation chemotherapy (first 36 days) and following 2 cycles (72 days) within the confines of a pilot study. (Cohort 2)

OUTLINE: Patients are assigned to 1 of 2 cohorts.

COHORT I: Patients receive inotuzumab ozogamicin intravenously (IV) over 60 minutes on days 1, 8, and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity. (COMPLETE)

COHORT II: Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15. Patients also receive cyclophosphamide IV over 30-60 on day 1; cytarabine IV over 1-30 minutes or subcutaneously (SC) on days 1-4 and 8-11; mercaptopurine orally (PO) once daily (QD) on days 1-14; leucovorin calcium PO or IV on days 2, 9, 16, 23 and 37 of cycle 1 and days 9 and 37 of cycle 2; pegaspargase IV over 1-2 hours or intramuscularly (IM) on day 22; and vincristine IV on days 22 and 29. Patients receive methotrexate intrathecally (IT) on days 1, 8 and 36 of cycle 1 and day 36 of cycle 2 for CNS 1 patients, days 1, 8, 15, 22 and 36 of cycle 1, and day 36 of cycle 2 for CNS 2 patients. CNS 3 patients receive methotrexate intrathecal triple therapy (ITT) IT on days 1, 8, 15, 22 and 36 of cycle 1 and days 8 and 36 of cycle 2. There will be 3 dose levels. If excessive toxicity is observed at dose level 1, the dosing of inotuzumab ozogamicin will be decreased for dose level -1. If excessive toxicity is observed at this dose, then for dose level -2, vincristine and pegaspargase will be omitted. Treatment repeats every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days, every 3 months for 1 year, and then yearly for 4 years.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
87 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 2 Study of Inotuzumab Ozogamicin (NSC# 772518) in Children and Young Adults With Relapsed or Refractory CD22+ B-Acute Lymphoblastic Leukemia (B-ALL)
Actual Study Start Date :
Jun 5, 2017
Anticipated Primary Completion Date :
Dec 31, 2022
Anticipated Study Completion Date :
Dec 31, 2022

Arms and Interventions

Arm Intervention/Treatment
Experimental: Cohort I (inotuzumab ozogamicin)

Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15 of each cycle. Treatment repeats every 28 days for up to 6 cycles in the absence of disease progression or unacceptable toxicity.

Biological: Inotuzumab Ozogamicin
Given IV

Experimental: Cohort II (inotuzumab ozogamicin, mBFM chemotherapy)

Patients receive inotuzumab ozogamicin IV over 60 minutes on days 1, 8, and 15. Patients also receive cyclophosphamide IV over 30-60 on day 1; cytarabine IV over 1-30 minutes or SC on days 1-4 and 8-11; mercaptopurine PO QD on days 1-14; leucovorin calcium PO or IV on days 2, 9, 16, 23 and 37 of cycle 1 and days 9 and 37 of cycle 2; pegaspargase IV over 1-2 hours or IM on day 22; and vincristine IV on days 22 and 29. Patients receive methotrexate IT on days 1, 8 and 36 of cycle 1 and day 36 of cycle 2 for CNS 1 patients, days 1, 8, 15, 22 and 36 of cycle 1, and day 36 of cycle 2 for CNS 2 patients. CNS 3 patients receive methotrexate ITT IT on days 1, 8, 15, 22 and 36 of cycle 1 and days 8 and 36 of cycle 2. Patients assigned to inotuzumab ozogamicin dose level -2 do not receive vincristine and pegaspargase. Treatment repeats every 36 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity.

Drug: Cyclophosphamide
Given IV

Drug: Cytarabine
Given IV or SC

Biological: Inotuzumab Ozogamicin
Given IV

Drug: Leucovorin Calcium
Given PO or IV

Drug: Mercaptopurine
Given PO

Drug: Methotrexate
Given IT

Drug: Pegaspargase
Given IV or IM

Drug: Vincristine
Given IV

Outcome Measures

Primary Outcome Measures

  1. Morphologic response (complete response [CR]+ incomplete hematologic recovery [CRi]) following one cycle of treatment with inotuzumab ozogamicin (Cohort 1) [Up to 28 days]

    The response rate will be estimated using the proportion of eligible/evaluable patients with CR/CRi response. A one-sided lower 95% Agresti-Coull confidence limit will be calculated.

Secondary Outcome Measures

  1. Morphologic response (CR + CRi) following 2 cycles of inotuzumab ozogamicin therapy (Cohort1) [Up to 56 days]

    The response rate will be estimated using the proportion of eligible/evaluable patients with CR/CRi response.

  2. Incidence of dose-limiting toxicities at recommended phase II dose (RP2D) (Cohort 1) [During Cycle 1, up to 42 days]

    Evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. For a given reporting period, a patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient.

  3. Level of minimal residual disease (MRD) assessed in bone marrow by flow cytometry (Cohort 1 and 2) [Up to 2 cycles]

    MRD negativity rates (< 0.01% detectable leukemia cells) will be estimated.

  4. Incidence of adverse events of sinusoidal obstruction syndrome (SOS) of liver (Cohort 1 and 2) [Up to 1 year from last dose of Inotuzumab ozogamicin]

    Evaluated according to NCI CTCAE version 5.0. The incidence of SOS of the liver in patients during inotuzumab ozogamicin therapy and following subsequent treatment including myeloablative hematopoietic cell transplantation (HSCT) will be described.

  5. Event free survival (EFS) (Cohort 1) [From study entry to first event (induction failure, induction death, relapse, second malignancy, remission death), or date of last follow-up for event free subjects, assessed up to 5 years]

    Standard errors and confidence intervals for EFS will be calculated using Peto's method.

  6. Overall survival (Cohort 1) [From the time from study entry to death or date of last follow-up, assessed up to 3 years]

    OS will be estimated using Kaplan Meier approach.

  7. Duration of CR, CRi (Cohort 1) [Up to 3 years]

    Among responding patients, three-year complete continuous response will also be estimated using duration of CR/CRi for the overall responding group and stratified by whether or not the patients proceed to HSCT.

  8. Pharmacokinetic (PK) parameters, i.e., inotuzumab ozogamicin trough levels (Cohort 1) [Cycles 1 and 2 (each cycle is 28 days)]

    Inotuzumab ozogamicin trough levels (ng/mL) will be determined in serum by validated, high sensitivity liquid chromatography-mass spectrometry (LCMS) assays. Descriptive summary statistics will be provided for the trough levels at scheduled visits for Cycles 1 and 2.

  9. Immunogenicity (Cohort 1) [Cycles 1 and 2]

    Enhanced chemiluminescence (ECL) and cell-based assays will be used to detect anti-drug antibodies and neutralizing antibodies to inotuzumab ozogamicin in serum. Inotuzumab ozogamicin trough levels will be compared between patients with and without antibodies.

  10. Incidence of dose-limiting toxicities at the selected dose level of inotuzumab ozogamicin in combination with the augmented modified Berlin-Frankfurt-Munster (mBFM) consolidation chemotherapy (Cohort 2) [Up to cycle 1 (each cycle is 36 days)]

    Evaluated according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Toxicity tables will be constructed to summarize the observed incidence by type of toxicity and grade. For a given reporting period, a patient will be counted only once for a given toxicity for the worst grade of that toxicity reported for that patient.

Other Outcome Measures

  1. Changes in CD22 surface expression (Cohorts 1 and 2) [Baseline, post Cycle 1, and at time of relapse]

    Exploratory analysis of CD22 will focus primarily on the comparison of paired pre-treatment and post-treatment samples at the following times, 1) End of cycle 1 and 2) at relapse to evaluate for changes in CD22 expression pre and post-inotuzumab ozogamicin. Specifically, samples will be evaluated for change in CD22 expression that occurs over time to study the role of CD22 expression as it relates to resistance to therapy or mechanism for relapse. Correlation between changes in CD22 expression and patient's clinical response to inotuzumab ozogamicin as well as cytogenetic/molecular features will be described, in particular to explore the association of CD22-negative subpopulations in patients with KMT2A-rearranged acute lymphoblastic leukemia (ALL).

  2. Change in CD22 site density (Cohorts 1 and 2) [Baseline, post Cycle 1, and at time of relapse]

    Exploratory analysis of CD22 will focus primarily on the comparison of paired pre-treatment and post-treatment samples at the following times, 1) End of cycle 1 and 2) at relapse to evaluate for changes in CD22 site density pre and post-inotuzumab ozogamicin. Samples will be evaluated for any change in CD22 site density that occurs over time and to evaluate for the emergence of a CD22 "dim" or "negative" population to study the role of CD22 site density as it relates to resistance to therapy or mechanism for relapse. Correlation between changes in CD22 site density and patient's clinical response to inotuzumab ozogamicin as well as cytogenetic/molecular features will be described, in particular to explore the association of CD22-negative subpopulations in patients with KMT2A-rearranged acute lymphoblastic leukemia (ALL).

  3. Leukemic blast CD22 splice variants (Cohorts 1 and 2) [Baseline, post-Cycle 1, and at time of relapse]

    Will be analyzed by ribonucleic acid-sequencing (RNA-Seq). The MAJIQ and VOILA software will be used to identify splicing variations in CD22 from RNA Seq and to quantitate the percent spliced in (PSI) of the alternative exons. CD22 protein levels will be determined by immunoblotting of whole cell protein lysates using several anti-CD22 antibodies recognizing either extracellular or intracellular domains. Both protein sizes and preservation of individual epitopes will be assessed and correlated with alterations in exon inclusion.

  4. Intracellular signaling pathways in leukemic blasts treated with inotuzumab ozogamicin (Cohorts 1 and 2) [Baseline up to 5 years]

    Peripheral blood samples will be evaluated by comprehensive protein profiling using CyTOF panels for the two major areas of analyses, surface immunophenotyping to assess the developmental stage of both normal and abnormal B cells and measure their responses to inotuzumab ozogamicin , as well as intracellular epitopes to assess the cellular consequences of treatment with inotuzumab ozogamicin. Exploratory analysis will be performed using Cytobank software tools (viSNE, SPADE and CITRUS) for subpopulations clustering, dimensionality reduction and hierarchical organization.

  5. Changes in peripheral blood absolute B cell numbers and maturation of developing B cell populations with inotuzumab ozogamicin therapy (Cohorts 1 and 2) [Baseline up to 5 years]

    Descriptive statistics will be used to characterize patterns of B-cell development including selective loss of subsets. Changes in B cell number and subsets will be described, and exploratory analysis will be conducted to assess their correlation with clinical features including immunoglobulin levels, occurrence of infections, and need for intravenous immunoglobulin (IVIG) replacement during inotuzumab ozogamicin therapy.

  6. Level of MRD by next-generation high-throughput sequencing (HTS) techniques (Cohorts 1 and 2) [Up to 2 cycles]

    Compared to MRD measured by flow cytometry. MRD levels at each bone marrow evaluation time point will be measured by standard flow cytometry (MRD-negative defined as < 0.01% or 1 leukemic cell in 10-4 nucleated cells). At the end of cycles 1 and 2, MRD will also be assessed by HTS. The correlation between the measurements with each technique will be described and the sensitivity of flow-based MRD methodology in the setting of CD22-targeted therapy will be explored.

  7. Serum levels of candidate SOS biomarkers Ang2 and L ficolin (Cohorts 1 and 2) [Up to 12 months from last dose of inotuzumab ozogamicin]

    Correlated with clinical development of SOS. Descriptive statistics will be used to characterize clinical features of patients experiencing SOS. L-ficolin and Ang2 absolute levels and change in level over time with inotuzumab ozogamicin exposure will be evaluated and correlated with development of SOS. Biomarker levels will be compared using simple comparative statistics between subgroups.

  8. Incidence of SOS in patients who receive prophylaxis with ursodeoxycholic acid (UDCA) during inotuzumab ozogamicin therapy (Cohorts 1 and 2) [Up to 12 months from last dose of inotuzumab ozogamicin]

    Descriptive statistics will be used to characterize clinical features of patients experiencing SOS, potential clinical risk factors, and the impact of ursodeoxycholic acid prophylaxis.

  9. Interaction between CAR- T therapy and inotuzumab ozogamicin (Cohorts 1 and 2) [Up to 5 years]

    Will be evaluated by incidence of hematologic DLT in patients with CAR-T therapy prior to inotuzumab ozogamicin, incidence of post-inotuzumab ozogamicin CAR-T therapy, time to CAR-T therapy after inotuzumab ozogamicin, and B-cell recovery prior to CAR-T therapy after inotuzumab ozogamicin. Will be summarized using descriptive statistics.

  10. Morphologic response (CR/CRi) (Cohort 2) [Up to 2 cycles (each cycle is 36 days)]

    Will be estimated using the proportion of eligible/evaluable patients with CR/CRi response. Analysis will be mostly descriptive.

Eligibility Criteria

Criteria

Ages Eligible for Study:
1 Year to 21 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Patients must be >= 1 year and < 22 years of age at the time of enrollment

  • Patients must have B-ALL, or previously diagnosed B lymphoblastic lymphoma (B-LL), with >= 5% (M2 or M3) bone marrow blasts with or without extramedullary disease

  • NOTE: Relapsed patients previously diagnosed with B-lymphoblastic lymphoma (B-LL) are eligible if they have an M2 or M3 marrow at the time of enrollment on this study

  • Patients with ALL or B-LL who have M2 morphology must have local confirmatory testing showing >= 5% blasts by flow cytometry, fluorescence in situ hybridization (FISH) testing or other molecular method

  • Leukemic blasts must demonstrate surface expression of CD22 at the time of relapse by local/institutional flow cytometry of a bone marrow aspirate sample; (assessment of CD22 using a bright fluorophore such as phycoerythrin [PE] is strongly recommended)

  • In the case of an inadequate aspirate sample (dry tap) or if bone marrow aspirate is unable to be performed due to patient clinical status, flow cytometry of peripheral blood specimen may be substituted if the patient has at least 1,000/uL circulating blasts; alternatively, CD22 expression may be documented by immunohistochemistry of a bone marrow biopsy specimen

  • Patients with one of the following:

  • Second or greater relapse;

  • Primary refractory disease with at least 2 prior induction attempts;

  • First relapse refractory to at least one prior re-induction attempt

  • Any relapse after HSCT (Cohort 1 ONLY)

Patients with Down syndrome are eligible ONLY for Cohort 1 with:
  • Any of above disease status, OR

  • First relapse with no prior re-induction attempt NOTE: Patients with Down syndrome or prior HSCT are NOT eligible for Cohort 2 combination therapy

  • Patients with Philadelphia chromosome (Ph)+ ALL must have had two prior therapy attempts including two different tyrosine kinase inhibitors (TKIs)

  • Patients must have fully recovered from the acute toxic effects of all prior anti-cancer therapy, defined as resolution of all such toxicities to =< grade 2 or lower per the inclusion/exclusion criteria prior to entering this study. Apply to Cohort 2:

  • Cytotoxic chemotherapy or other anti-cancer agents known to be myelosuppressive. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned Research Coordinator prior to enrollment.

  • A waiting period prior to enrollment is not required for patients receiving standard cytotoxic maintenance chemotherapy (i.e., corticosteroid, vincristine, 6MP, and/or methotrexate).

  • A waiting period is not required for patients receiving a single dose of intrathecal methotrexate, hydrocortisone, and/or cytarabine within 7 days prior to enrollment

  • = 14 days must have elapsed after the completion of other cytotoxic therapy, with the exception of hydroxyurea, for patients not receiving standard maintenance therapy. Additionally, patients must have fully recovered from all acute toxic effects of prior therapy.

  • Note: Cytoreduction with hydroxyurea must be discontinued >= 24 hours prior to the start of protocol therapy.

  • Anti-cancer agents not known to be myelosuppressive (e.g., not associated with reduced platelet or absolute neutrophil count [ANC] counts): >= 7 days after the last dose of agent. For agents not listed, the duration of this interval must be discussed with the study chair and the study-assigned research coordinator prior to enrollment.

  • Anti-cancer agents that are antibodies: >= 21 days must have elapsed from infusion of last dose of antibody, and toxicity related to prior antibody therapy must be recovered to grade =< 1. There is an exception for blinatumomab infusions, for which patients must have been off for at least 3 days and all drug related toxicity must have resolved to grade 2 or lower as outlined in the inclusion/exclusion criteria.

  • Corticosteroids: If used to modify immune adverse events related to prior therapy, >= 14 days must have elapsed since last dose of corticosteroid. A waiting period prior to enrollment is not required for patients receiving corticosteroid for leukemia therapy/cytoreduction.

  • Radiotherapy: >= 2 weeks must have elapsed since local palliative radiation therapy (XRT) (small port); >= 3 months must have elapsed if prior cranial or craniospinal XRT was received, if >= 50% of the pelvis was irradiated, or if total body irradiation (TBI) was received; >= 6 weeks must have elapsed if other substantial bone marrow irradiation was given.

  • Stem cell transplant or rescue without TBI: For Cohort 1, at least 90 days must have elapsed since stem cell transplant and at least 30 days from donor lymphocyte infusion. Patient must have had no more than one previous HSCT and currently have no evidence of active graft vs. host disease (GVHD). For Cohort 2, no prior HSCT is allowed.

  • Chimeric antigen receptor (CAR) T cell therapy: At least 30 days must have elapsed from the last CAR-T cell infusion

  • Patients must have a performance status corresponding to Eastern Cooperative Oncology Group (ECOG) scores of 0, 1, or 2; use Karnofsky for patients > 16 years of age and Lansky for patients =< 16 years of age; patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score

  • Creatinine clearance or radioisotope glomerular filtration rate (GFR) >= 70 mL/min/1.73 m^2 or

  • A serum creatinine based on age/gender as follows:

  • 1 to < 2 years: maximum serum creatinine 0.6 mg/dL (both male and female)

  • 2 to < 6 years: maximum serum creatinine 0.8 mg/dL (both male and female)

  • 6 to < 10 years: maximum serum creatinine 1 mg/dL (both male and female)

  • 10 to < 13 years: maximum serum creatinine 1.2 mg/dL (both male and female)

  • 13 to < 16 years: maximum serum creatinine 1.5 mg/dL (male), 1.4 mg/dL (female)

  • = 16 years: maximum serum creatinine 1.7 mg/dL (male), 1.4 mg/dL (female)

  • Direct bilirubin =< 1.5 x upper limit of normal (ULN) for age, and

  • Serum glutamic pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) =< 5 x ULN for age; for the purpose of this study, the ULN for ALT will be 45 U/L

Exclusion Criteria:
  • Patients with any prior history of SOS irrespective of severity

  • Patients with isolated central nervous system (CNS), testicular, or any other extramedullary site of relapse

  • Patients who have been previously treated with inotuzumab ozogamicin

  • Patients who have previously received HSCT (Cohort 2 only)

  • Patients with Down syndrome (Cohort 2 only)

  • History of allergic reaction attributed to compounds of similar or biologic composition to inotuzumab ozogamicin or other agents in the study

  • Note: Patients with history of allergy to pegaspargase are eligible for enrollment on Cohort 2 (dose levels 1 and -1) if asparaginase Erwinia can be obtained

  • If Cohort 2 is enrolling at dose level -2, then patients who cannot receive asparaginase due to prior allergy, toxicity, or lack of access may enroll

  • NOTE: patients on AALL1621 are not eligible to co-enroll on AALL1931

  • Patients with active optic nerve and/or retinal involvement are not eligible; patients who are presenting with visual disturbances should have an ophthalmologic exam and, if indicated, a magnetic resonance imaging (MRI) to assess optic nerve or retinal involvement

  • Patients who are currently receiving another investigational drug

  • Patients who are currently receiving or plan to receive other anti-cancer agents (except hydroxyurea, which may be continued until 24 hours prior to start of protocol therapy, and intrathecal chemotherapy)

  • Anti-GVHD or agents to prevent organ rejection post-transplant; patients who are receiving cyclosporine, tacrolimus, or other agents to prevent either graft-versus-host disease post bone marrow transplant or organ rejection post-transplant are not eligible for this trial; at least 3 half-lives must have elapsed after the last dose of GVHD medications (meds)

  • Patients who are currently receiving or plan to receive corticosteroids except as described below

  • Systemic corticosteroids may be administered for cytoreduction up to 24 hours prior to the start of protocol therapy, (Cohort 1 only) for all patients, corticosteroids may be administered as a premedication for inotuzumab ozogamicin and as treatment for allergic reactions or for physiologic replacement/stress dosing of hydrocortisone for documented adrenal insufficiency; corticosteroids are not allowed for other indications

  • Patients with known human immunodeficiency virus (HIV), hepatitis B or C infections; testing to prove negative status is not required for enrollment unless it is deemed necessary for usual medical care of the patient

  • Patients who have an active uncontrolled infection defined as:

  • Positive bacterial blood culture within 48 hours of study enrollment;

  • Fever above 38.2 degree Celsius (C) within 48 hours of study enrollment with clinical signs of infection; fever that is determined to be due to tumor burden is allowed if patients have documented negative blood cultures for at least 48 hours prior to enrollment and no concurrent signs or symptoms of active infection or hemodynamic instability

  • A positive fungal culture within 30 days of study enrollment or active therapy for presumed invasive fungal infection

  • Patients may be receiving IV or oral antibiotics to complete a course of therapy for a prior documented infection as long as cultures have been negative for at least 48 hours and signs or symptoms of active infection have resolved; for patients with clostridium (C.) difficile diarrhea, at least 72 hours of antibacterial therapy must have elapsed and stools must have normalized to baseline

  • Active viral or protozoal infection requiring IV treatment

  • Patients known to have one of the following concomitant genetic syndromes: Bloom syndrome, ataxia-telangiectasia, Fanconi anemia, Kostmann syndrome, Schwachman (Schwachman-Diamond-Blackfan) syndrome or any other known bone marrow failure syndrome

  • There have been no human studies of inotuzumab ozogamicin in pregnant women and no reports of exposure in utero; based on nonclinical safety studies, inotuzumab ozogamicin has the potential to impair human male and female fertility and to adversely affect human embryo fetal development; women of childbearing potential should be advised to avoid becoming pregnant while receiving inotuzumab ozogamicin; there is no information regarding the presence of inotuzumab ozogamicin in human milk, the effects on the breast-fed infant, or the effects on milk production; because of the potential for adverse reactions in breast-fed infants, women should not breast-feed during treatment with inotuzumab ozogamicin and for at least 2 months after the final dose

  • Female patients of childbearing potential are not eligible unless a negative pregnancy test result has been obtained within 7 days prior to enrollment

  • Female patients who are sexually active and of reproductive potential are not eligible unless they agree to use an effective contraceptive method for the duration of their study participation and for 8 months after the last dose of inotuzumab ozogamicin

  • Men with female partners of childbearing potential should use effective contraception during treatment with inotuzumab ozogamicin and for at least 5 months after the last dose of inotuzumab ozogamicin

  • Lactating females are not eligible unless they agree not to breastfeed their infants

Contacts and Locations

Locations

Site City State Country Postal Code
1 Children's Hospital of Alabama Birmingham Alabama United States 35233
2 Providence Alaska Medical Center Anchorage Alaska United States 99508
3 Banner Children's at Desert Mesa Arizona United States 85202
4 Phoenix Childrens Hospital Phoenix Arizona United States 85016
5 Banner University Medical Center - Tucson Tucson Arizona United States 85719
6 Arkansas Children's Hospital Little Rock Arkansas United States 72202-3591
7 Kaiser Permanente Downey Medical Center Downey California United States 90242
8 City of Hope Comprehensive Cancer Center Duarte California United States 91010
9 Loma Linda University Medical Center Loma Linda California United States 92354
10 Children's Hospital Los Angeles Los Angeles California United States 90027
11 Valley Children's Hospital Madera California United States 93636
12 UCSF Benioff Children's Hospital Oakland Oakland California United States 94609
13 Kaiser Permanente-Oakland Oakland California United States 94611
14 Children's Hospital of Orange County Orange California United States 92868
15 Lucile Packard Children's Hospital Stanford University Palo Alto California United States 94304
16 Sutter Medical Center Sacramento Sacramento California United States 95816
17 University of California Davis Comprehensive Cancer Center Sacramento California United States 95817
18 Rady Children's Hospital - San Diego San Diego California United States 92123
19 UCSF Medical Center-Mission Bay San Francisco California United States 94158
20 Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center Torrance California United States 90502
21 Children's Hospital Colorado Aurora Colorado United States 80045
22 Rocky Mountain Hospital for Children-Presbyterian Saint Luke's Medical Center Denver Colorado United States 80218
23 Connecticut Children's Medical Center Hartford Connecticut United States 06106
24 Yale University New Haven Connecticut United States 06520
25 Alfred I duPont Hospital for Children Wilmington Delaware United States 19803
26 Children's National Medical Center Washington District of Columbia United States 20010
27 Golisano Children's Hospital of Southwest Florida Fort Myers Florida United States 33908
28 University of Florida Health Science Center - Gainesville Gainesville Florida United States 32610
29 Memorial Regional Hospital/Joe DiMaggio Children's Hospital Hollywood Florida United States 33021
30 Nemours Children's Clinic-Jacksonville Jacksonville Florida United States 32207
31 Nicklaus Children's Hospital Miami Florida United States 33155
32 AdventHealth Orlando Orlando Florida United States 32803
33 Nemours Children's Hospital Orlando Florida United States 32827
34 Johns Hopkins All Children's Hospital Saint Petersburg Florida United States 33701
35 Saint Joseph's Hospital/Children's Hospital-Tampa Tampa Florida United States 33607
36 Saint Mary's Hospital West Palm Beach Florida United States 33407
37 Children's Healthcare of Atlanta - Egleston Atlanta Georgia United States 30322
38 Memorial Health University Medical Center Savannah Georgia United States 31404
39 Kapiolani Medical Center for Women and Children Honolulu Hawaii United States 96826
40 Saint Luke's Cancer Institute - Boise Boise Idaho United States 83712
41 Lurie Children's Hospital-Chicago Chicago Illinois United States 60611
42 University of Chicago Comprehensive Cancer Center Chicago Illinois United States 60637
43 Loyola University Medical Center Maywood Illinois United States 60153
44 Saint Jude Midwest Affiliate Peoria Illinois United States 61637
45 Southern Illinois University School of Medicine Springfield Illinois United States 62702
46 Riley Hospital for Children Indianapolis Indiana United States 46202
47 Saint Vincent Hospital and Health Care Center Indianapolis Indiana United States 46260
48 Blank Children's Hospital Des Moines Iowa United States 50309
49 University of Iowa/Holden Comprehensive Cancer Center Iowa City Iowa United States 52242
50 University of Kentucky/Markey Cancer Center Lexington Kentucky United States 40536
51 Norton Children's Hospital Louisville Kentucky United States 40202
52 Children's Hospital New Orleans New Orleans Louisiana United States 70118
53 Ochsner Medical Center Jefferson New Orleans Louisiana United States 70121
54 Eastern Maine Medical Center Bangor Maine United States 04401
55 Maine Children's Cancer Program Scarborough Maine United States 04074
56 Sinai Hospital of Baltimore Baltimore Maryland United States 21215
57 Johns Hopkins University/Sidney Kimmel Cancer Center Baltimore Maryland United States 21287
58 National Institutes of Health Clinical Center Bethesda Maryland United States 20892
59 Tufts Children's Hospital Boston Massachusetts United States 02111
60 Dana-Farber Cancer Institute Boston Massachusetts United States 02215
61 UMass Memorial Medical Center - University Campus Worcester Massachusetts United States 01655
62 C S Mott Children's Hospital Ann Arbor Michigan United States 48109
63 Michigan State University Clinical Center East Lansing Michigan United States 48824-7016
64 Helen DeVos Children's Hospital at Spectrum Health Grand Rapids Michigan United States 49503
65 Beaumont Children's Hospital-Royal Oak Royal Oak Michigan United States 48073
66 Children's Hospitals and Clinics of Minnesota - Minneapolis Minneapolis Minnesota United States 55404
67 University of Minnesota/Masonic Cancer Center Minneapolis Minnesota United States 55455
68 Mayo Clinic in Rochester Rochester Minnesota United States 55905
69 University of Mississippi Medical Center Jackson Mississippi United States 39216
70 Columbia Regional Columbia Missouri United States 65201
71 Children's Mercy Hospitals and Clinics Kansas City Missouri United States 64108
72 Cardinal Glennon Children's Medical Center Saint Louis Missouri United States 63104
73 Washington University School of Medicine Saint Louis Missouri United States 63110
74 Mercy Hospital Saint Louis Saint Louis Missouri United States 63141
75 Children's Hospital and Medical Center of Omaha Omaha Nebraska United States 68114
76 University of Nebraska Medical Center Omaha Nebraska United States 68198
77 Sunrise Hospital and Medical Center Las Vegas Nevada United States 89109
78 Alliance for Childhood Diseases/Cure 4 the Kids Foundation Las Vegas Nevada United States 89135
79 Summerlin Hospital Medical Center Las Vegas Nevada United States 89144
80 Renown Regional Medical Center Reno Nevada United States 89502
81 Dartmouth Hitchcock Medical Center Lebanon New Hampshire United States 03756
82 Hackensack University Medical Center Hackensack New Jersey United States 07601
83 Morristown Medical Center Morristown New Jersey United States 07960
84 Saint Peter's University Hospital New Brunswick New Jersey United States 08901
85 Rutgers Cancer Institute of New Jersey-Robert Wood Johnson University Hospital New Brunswick New Jersey United States 08903
86 Newark Beth Israel Medical Center Newark New Jersey United States 07112
87 Saint Joseph's Regional Medical Center Paterson New Jersey United States 07503
88 Albany Medical Center Albany New York United States 12208
89 Roswell Park Cancer Institute Buffalo New York United States 14263
90 NYU Winthrop Hospital Mineola New York United States 11501
91 The Steven and Alexandra Cohen Children's Medical Center of New York New Hyde Park New York United States 11040
92 Laura and Isaac Perlmutter Cancer Center at NYU Langone New York New York United States 10016
93 Mount Sinai Hospital New York New York United States 10029
94 Memorial Sloan Kettering Cancer Center New York New York United States 10065
95 University of Rochester Rochester New York United States 14642
96 Stony Brook University Medical Center Stony Brook New York United States 11794
97 State University of New York Upstate Medical University Syracuse New York United States 13210
98 New York Medical College Valhalla New York United States 10595
99 Mission Hospital Asheville North Carolina United States 28801
100 UNC Lineberger Comprehensive Cancer Center Chapel Hill North Carolina United States 27599
101 Duke University Medical Center Durham North Carolina United States 27710
102 East Carolina University Greenville North Carolina United States 27834
103 Wake Forest University Health Sciences Winston-Salem North Carolina United States 27157
104 Sanford Broadway Medical Center Fargo North Dakota United States 58122
105 Children's Hospital Medical Center of Akron Akron Ohio United States 44308
106 Cincinnati Children's Hospital Medical Center Cincinnati Ohio United States 45229
107 Cleveland Clinic Foundation Cleveland Ohio United States 44195
108 Nationwide Children's Hospital Columbus Ohio United States 43205
109 Dayton Children's Hospital Dayton Ohio United States 45404
110 ProMedica Toledo Hospital/Russell J Ebeid Children's Hospital Toledo Ohio United States 43606
111 University of Oklahoma Health Sciences Center Oklahoma City Oklahoma United States 73104
112 Legacy Emanuel Children's Hospital Portland Oregon United States 97227
113 Oregon Health and Science University Portland Oregon United States 97239
114 Lehigh Valley Hospital-Cedar Crest Allentown Pennsylvania United States 18103
115 Geisinger Medical Center Danville Pennsylvania United States 17822
116 Penn State Children's Hospital Hershey Pennsylvania United States 17033
117 Children's Hospital of Philadelphia Philadelphia Pennsylvania United States 19104
118 Saint Christopher's Hospital for Children Philadelphia Pennsylvania United States 19134
119 Children's Hospital of Pittsburgh of UPMC Pittsburgh Pennsylvania United States 15224
120 Rhode Island Hospital Providence Rhode Island United States 02903
121 Prisma Health Richland Hospital Columbia South Carolina United States 29203
122 BI-LO Charities Children's Cancer Center Greenville South Carolina United States 29605
123 Sanford USD Medical Center - Sioux Falls Sioux Falls South Dakota United States 57117-5134
124 T C Thompson Children's Hospital Chattanooga Tennessee United States 37403
125 East Tennessee Childrens Hospital Knoxville Tennessee United States 37916
126 Saint Jude Children's Research Hospital Memphis Tennessee United States 38105
127 The Children's Hospital at TriStar Centennial Nashville Tennessee United States 37203
128 Vanderbilt University/Ingram Cancer Center Nashville Tennessee United States 37232
129 Dell Children's Medical Center of Central Texas Austin Texas United States 78723
130 Driscoll Children's Hospital Corpus Christi Texas United States 78411
131 Medical City Dallas Hospital Dallas Texas United States 75230
132 UT Southwestern/Simmons Cancer Center-Dallas Dallas Texas United States 75390
133 El Paso Children's Hospital El Paso Texas United States 79905
134 Cook Children's Medical Center Fort Worth Texas United States 76104
135 Baylor College of Medicine/Dan L Duncan Comprehensive Cancer Center Houston Texas United States 77030
136 UMC Cancer Center / UMC Health System Lubbock Texas United States 79415
137 Children's Hospital of San Antonio San Antonio Texas United States 78207
138 Methodist Children's Hospital of South Texas San Antonio Texas United States 78229
139 University of Texas Health Science Center at San Antonio San Antonio Texas United States 78229
140 Primary Children's Hospital Salt Lake City Utah United States 84113
141 University of Vermont and State Agricultural College Burlington Vermont United States 05405
142 University of Virginia Cancer Center Charlottesville Virginia United States 22908
143 Inova Fairfax Hospital Falls Church Virginia United States 22042
144 Children's Hospital of The King's Daughters Norfolk Virginia United States 23507
145 Seattle Children's Hospital Seattle Washington United States 98105
146 Providence Sacred Heart Medical Center and Children's Hospital Spokane Washington United States 99204
147 West Virginia University Healthcare Morgantown West Virginia United States 26506
148 Marshfield Medical Center-Marshfield Marshfield Wisconsin United States 54449
149 Children's Hospital of Wisconsin Milwaukee Wisconsin United States 53226
150 HIMA San Pablo Oncologic Hospital Caguas Puerto Rico 00726

Sponsors and Collaborators

  • Children's Oncology Group
  • National Cancer Institute (NCI)

Investigators

  • Principal Investigator: Maureen M O'Brien, Children's Oncology Group

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Children's Oncology Group
ClinicalTrials.gov Identifier:
NCT02981628
Other Study ID Numbers:
  • AALL1621
  • NCI-2016-01494
  • AALL1621
  • AALL1621
  • AALL1621
  • U10CA180886
First Posted:
Dec 5, 2016
Last Update Posted:
Jul 18, 2022
Last Verified:
Jun 1, 2022

Study Results

No Results Posted as of Jul 18, 2022