S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

Sponsor
Southwest Oncology Group (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01925131
Collaborator
National Cancer Institute (NCI) (NIH)
50
5
6
105
10
0.1

Study Details

Study Description

Brief Summary

This phase I trial studies the side effects and best dose of inotuzumab ozogamicin when given together with combination chemotherapy in treating patients with relapsed or refractory acute leukemia. Immunotoxins, such as inotuzumab ozogamicin, can find cancer cells that express cluster of differentiation (CD)22 and kill them without harming normal cells. Drugs used in chemotherapy, such as cyclophosphamide, vincristine sulfate, and prednisone, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving inotuzumab ozogamicin together with combination chemotherapy may kill more cancer cells.

Detailed Description

PRIMARY OBJECTIVES:
  1. To assess the safety of inotuzumab ozogamicin in combination with cyclophosphamide, vincristine (vincristine sulfate) and prednisone (CVP) and to determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia [B-ALL], mixed phenotype, and Burkitt's).
SECONDARY OBJECTIVES:
  1. To estimate the preliminary activity (response rate: complete remission [CR] + complete remission with incomplete count recovery [CRi]) of this combination in the expansion cohort.

  2. To estimate the frequency and severity of toxicities of this combination in this patient population.

OUTLINE: This is a dose-escalation study of inotuzumab ozogamicin.

Patients receive cyclophosphamide intravenously (IV) on day 1, vincristine sulfate IV on day 1, prednisone orally (PO) on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 2 months for 1 year, every 3 months for 1 year, and then every 6 months for 1 year.

Study Design

Study Type:
Interventional
Actual Enrollment :
50 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
S1312, A Phase I Study of Inotuzumab Ozogamicin (NSC-772518) in Combination With CVP (Cyclophosphamide, Vincristine, Prednisone) for Patients With Relapsed/Refractory CD22-Positive Acute Leukemia (Including B-ALL, Mixed Phenotypic Leukemia, and Burkitt's Leukemia)
Study Start Date :
Apr 1, 2014
Actual Primary Completion Date :
Jan 1, 2022
Anticipated Study Completion Date :
Jan 1, 2023

Arms and Interventions

Arm Intervention/Treatment
Experimental: Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 1

Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

Drug: cyclophosphamide
Given IV
Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
  • DeCortin
  • Deltra
  • Biological: inotuzumab ozogamicin
    Given IV
    Other Names:
  • CMC-544
  • Other: laboratory biomarker analysis
    Correlative studies

    Experimental: Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 2

    Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

    Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
  • DeCortin
  • Deltra
  • Biological: inotuzumab ozogamicin
    Given IV
    Other Names:
  • CMC-544
  • Other: laboratory biomarker analysis
    Correlative studies

    Experimental: Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 3

    Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

    Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
  • DeCortin
  • Deltra
  • Biological: inotuzumab ozogamicin
    Given IV
    Other Names:
  • CMC-544
  • Other: laboratory biomarker analysis
    Correlative studies

    Experimental: Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 4

    Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

    Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
  • DeCortin
  • Deltra
  • Biological: inotuzumab ozogamicin
    Given IV
    Other Names:
  • CMC-544
  • Other: laboratory biomarker analysis
    Correlative studies

    Experimental: Treatment (combination chemotherapy and inotuzumab ozogamicin) - Dose Level 5

    Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

    Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
  • DeCortin
  • Deltra
  • Biological: inotuzumab ozogamicin
    Given IV
    Other Names:
  • CMC-544
  • Other: laboratory biomarker analysis
    Correlative studies

    Experimental: Treatment (combination chemotherapy and inotuzumab ozogamicin) - MTD

    Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.

    Drug: cyclophosphamide
    Given IV
    Other Names:
  • CPM
  • CTX
  • Cytoxan
  • Endoxan
  • Endoxana
  • Drug: vincristine sulfate
    Given IV
    Other Names:
  • leurocristine sulfate
  • VCR
  • Vincasar PFS
  • Drug: prednisone
    Given PO
    Other Names:
  • DeCortin
  • Deltra
  • Biological: inotuzumab ozogamicin
    Given IV
    Other Names:
  • CMC-544
  • Other: laboratory biomarker analysis
    Correlative studies

    Outcome Measures

    Primary Outcome Measures

    1. MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia [28 days]

      To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia [B-ALL], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is < 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.

    Secondary Outcome Measures

    1. Response Rate (CR+CRi) Among Expansion Cohort [Up to 3 years]

      The response rate (CR + CRi) is defined as the rate of complete remission (CR) + complete remission with incomplete count recovery (CRi). Complete remission (CR) is defined as < 5% marrow aspirate blasts, neutrophils ≥ 1000/uL, platelets > 100,000/uL, no blasts in peripheral blood, and C1 Extramedullary disease status. C1 Extramedullary disease status is characterized by complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions for which the following must be true: for participants with at least one measurable lesion, all lesions must have reduced by 75% in sum of products of greatest diameters (SPD), have no new lesions, and the spleen and other previously enlarged organs must have regressed in size. Complete remission with incomplete platelet recovery (CRi) is defined the same as CR, except absolute neutrophil count may be <1000/uL and/or platelet count may be ≤ 100,000/uL.

    2. Frequency and Severity of Toxicities [Up to 3 years]

      Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • Patients must have a diagnosis of relapsed or refractory CD22-positive acute leukemia including B-ALL, mixed phenotype leukemia (biphenotypic), or Burkitt's leukemia based on World Health Organization (WHO) classification; patients with bilineal leukemia are excluded

    • Patients must have evidence of acute leukemia in their peripheral blood or bone marrow; patients must have >= 5% blasts in the peripheral blood or bone marrow within 14 days prior to registration; at least >= 20% of those blasts must be CD22-positive (surface) based on local immunophenotyping and histopathology

    • Patients must be refractory or have relapsed following prior induction therapy; a standard induction regimen is defined as any program of treatment that includes vincristine and prednisone or dexamethasone, cytarabine/anthracycline, or high dose cytarabine

    • For sites with the B1931022 pharmaceutical trial open, precursor B-cell ALL patients from that site may be eligible for S1312 providing they meet the following criteria:

    • Patient is in second salvage or more; OR

    • Patient was treated on the standard of care arm of B1931022 and failed therapy

    • Patients may have received prior allogeneic transplant or autologous transplant; however, patients with prior allogeneic bone marrow transplant will be eligible only if both of the following conditions are met:

    • The transplant must have been performed >= 90 days prior to registration

    • The patient must not have >= grade 2 acute graft versus host disease (GvHD) or either moderate or severe limited chronic GvHD within 14 days prior to registration

    • Patients known to have Philadelphia chromosome positive (Ph+) ALL must have either failed treatment or been intolerant to treatment with at least two second or third generation tyrosine kinase inhibitors

    • Patients must not have received prior treatment with inotuzumab ozogamicin; previous treatment with other anti-CD22 antibodies must have been completed at least 90 days prior to registration

    • Patients must have Zubrod performance status 0-2

    • Patients must not have received any chemotherapy, investigational agents, or undergone major surgery within 14 days prior to registration with the following exceptions:

    • Monoclonal antibodies must not have been received for 1 week prior to registration

    • Chimeric antigen receptor (CAR) T-cells must not have been received for 28 days prior to registration.

    • Steroids, hydroxyurea, vincristine, 6-mercaptopurine, methotrexate, thioguanine and intrathecal chemotherapy are permitted within any time frame prior to registration. FDA-approved TKIs may also be administered until 1 day prior to start of study therapy (C1, D1).

    • All drug-related toxicities must have resolved to =< grade 2

    • Patients must not have a systemic bacterial, fungal, or viral infection that is not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement despite appropriate antibiotics or other treatment)

    • Patients must not have any other serious concurrent disease or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that would put the patient at undue risk of undergoing therapy

    • Patients must not have active central nervous system (CNS) involvement (by clinical evaluation); patients with previous documented history of CNS involvement of acute leukemia, or with clinical signs or symptoms consistent with CNS involvement of acute leukemia, must have a lumbar puncture which is negative for CNS involvement of acute leukemia; the lumbar puncture must be completed within 14 days prior to registration; patients with no previous history of documented CNS involvement and with no clinical signs or symptoms consistent with CNS involvement are not required to have completed a lumbar puncture before registration; note that treatment with intrathecal therapy is recommended during protocol treatment but CNS analysis during treatment is not required

    • Patients must have a peripheral blast count < 25,000/uL within 2 days prior to registration; (treatment with hydroxyurea and steroids is permitted to bring the countdown)

    • Patients must have serum creatinine =< 2 x institutional upper limits of normal (IULN) within 7 days prior to registration

    • Patients must have bilirubin =< 2 x IULN within 7 days prior to registration (unless the bilirubin is primarily unconjugated)

    • Patients must have < grade 2 neuropathy (sensory/motor) within 7 days prior to registration

    • Patients must have serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 2.5 x IULN within 7 days prior to registration

    • Patients with a history of a serious allergic or anaphylactic reaction to humanized monoclonal antibodies are not eligible

    • Patients must not have a history of chronic or active hepatitis B or C infection; patients must have negative hepatitis B and C serologies performed within 28 days prior to registration

    • Patients must not have evidence or history of veno-occlusive disease or sinusoidal obstruction syndrome

    • Patients must not have a cardiac ejection fraction < 45% or the presence of New York Heart Association stage III or IV heart failure within 14 days prior to registration; either echocardiogram (ECHO) or multiple-gated acquisition scan (MUGA) may be used to determine ejection fraction

    • Patients must not have a myocardial infarction within 6 months prior to registration

    • Patients must not have a history of clinically significant arrhythmia, prolonged corrected QT (QTc) interval, or unexplained syncope not thought to be vasovagal in nature within 6 months prior to registration

    • Patients must not have a screening corrected QT using Fridericia's formula (QTcF) interval > 500 milliseconds (by Fridericia calculation) based on the average of triplicate electrocardiogram (EKG) performed within 7 days prior to registration; note that triplicate EKG is required at other timepoints

    • Patients must not have a history of chronic liver disease (or cirrhosis)

    • Patients who are known to be human immunodeficiency virus (HIV)+ are eligible providing they meet all of the following additional criteria within 28 days prior to registration:

    • CD4+ cells >= 350/mm^3 (nadir)

    • Viral load of < 50 copies HIV messenger ribonucleic acid (mRNA)/mm^3 if on combination antiretroviral therapy (cART) or < 25,000 copies HIV mRNA if not on cART

    • No zidovudine or stavudine as part of cART Patients who are HIV+ and do not meet all of these criteria are not eligible for this study

    • Patients with evidence of extramedullary disease at diagnosis will have computed tomography (CT) scan of the chest, abdomen and pelvis to obtain baseline values within 28 days prior to registration

    • Patients must have complete history and physical examination within 28 days prior to registration

    • Patients must not be pregnant or nursing; women/men of reproductive potential must have agreed to use an effective contraceptive method; a woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months; in addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation; however, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures

    • Prior malignancy other than acute leukemia is allowed, provided it is in remission and there is no plan to treat the malignancy at the time of registration

    • Pretreatment cytogenetics must be performed on all patients; collection of pretreatment specimens must be completed within 14 days prior to registration to S1312; specimens must be submitted to the site's preferred Clinical Laboratory Improvement Amendments (CLIA)-approved cytogenetics laboratory; reports of the results must be submitted as described; note that cytogenetics are required at other time points

    • Patients or their legally authorized representative must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines

    • As a part of the OPEN registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system

    • Patients planning to enroll in this study must first have a slot reserved in advance of the registration; all site staff will use OPEN to create a slot reservation

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 City of Hope Comprehensive Cancer Center Duarte California United States 91010
    2 Stanford Cancer Institute Palo Alto Palo Alto California United States 94304
    3 University of Rochester Rochester New York United States 14642
    4 Cleveland Clinic Foundation Cleveland Ohio United States 44195
    5 Ben Taub General Hospital Houston Texas United States 77030

    Sponsors and Collaborators

    • Southwest Oncology Group
    • National Cancer Institute (NCI)

    Investigators

    • Principal Investigator: Anjali Advani, Southwest Oncology Group

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT01925131
    Other Study ID Numbers:
    • S1312
    • NCI-2013-01368
    • S1312
    • U10CA180888
    • U10CA032102
    First Posted:
    Aug 19, 2013
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail There were a total of 50 participants enrolled. However, two were deemed ineligible due to inadequate liver function and did not start protocol treatment, leaving 48 eligible participants.
    Arm/Group Title CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD (Expansion Cohort)
    Arm/Group Description Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose (Expansion Cohort) Patients receive 750 mg/m2 cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    Period Title: Overall Study
    STARTED 5 4 10 5 11 13
    COMPLETED 0 2 1 0 0 3
    NOT COMPLETED 5 2 9 5 11 10

    Baseline Characteristics

    Arm/Group Title CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD Total
    Arm/Group Description Combination chemotherapy and inotuzumab ozogamicin � Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Total of all reporting groups
    Overall Participants 5 4 10 5 11 13 48
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    48.8
    42.3
    42.8
    49.6
    37.9
    43.5
    43
    Sex: Female, Male (Count of Participants)
    Female
    1
    20%
    4
    100%
    4
    40%
    2
    40%
    5
    45.5%
    5
    38.5%
    21
    43.8%
    Male
    4
    80%
    0
    0%
    6
    60%
    3
    60%
    6
    54.5%
    8
    61.5%
    27
    56.3%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    2
    40%
    2
    50%
    2
    20%
    4
    80%
    3
    27.3%
    3
    23.1%
    16
    33.3%
    Not Hispanic or Latino
    3
    60%
    2
    50%
    7
    70%
    1
    20%
    6
    54.5%
    9
    69.2%
    28
    58.3%
    Unknown or Not Reported
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    2
    18.2%
    1
    7.7%
    4
    8.3%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Asian
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    3
    23.1%
    4
    8.3%
    Native Hawaiian or Other Pacific Islander
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Black or African American
    1
    20%
    1
    25%
    2
    20%
    0
    0%
    1
    9.1%
    0
    0%
    5
    10.4%
    White
    4
    80%
    3
    75%
    6
    60%
    5
    100%
    7
    63.6%
    8
    61.5%
    33
    68.8%
    More than one race
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Unknown or Not Reported
    0
    0%
    0
    0%
    2
    20%
    0
    0%
    2
    18.2%
    2
    15.4%
    6
    12.5%

    Outcome Measures

    1. Primary Outcome
    Title MTD of Inotuzumab Ozogamicin With CVP for Patients With Relapsed or Refractory CD22+ Acute Leukemia
    Description To determine the maximum tolerated dose (MTD) of inotuzumab ozogamicin in this regimen for patients with relapsed or refractory CD22+ acute leukemia (B-cell acute lymphoblastic leukemia [B-ALL], mixed phenotype, and Burkitt's). The MTD is defined as the highest dose studied in which the incidence of dose-limiting toxicities is < 33% using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.0.
    Time Frame 28 days

    Outcome Measure Data

    Analysis Population Description
    Includes eligible patients who received treatment among all arms.
    Arm/Group Title CVP + Inotuzumab
    Arm/Group Description Combination chemotherapy and inotuzumab ozogamicin Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour on days 1, 8, and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 48
    Day 1 Dose
    0.8
    Day 8 Dose
    0.5
    Day 15 Dose
    0.5
    2. Secondary Outcome
    Title Response Rate (CR+CRi) Among Expansion Cohort
    Description The response rate (CR + CRi) is defined as the rate of complete remission (CR) + complete remission with incomplete count recovery (CRi). Complete remission (CR) is defined as < 5% marrow aspirate blasts, neutrophils ≥ 1000/uL, platelets > 100,000/uL, no blasts in peripheral blood, and C1 Extramedullary disease status. C1 Extramedullary disease status is characterized by complete disappearance of all measurable and non-measurable extramedullary disease with the exception of lesions for which the following must be true: for participants with at least one measurable lesion, all lesions must have reduced by 75% in sum of products of greatest diameters (SPD), have no new lesions, and the spleen and other previously enlarged organs must have regressed in size. Complete remission with incomplete platelet recovery (CRi) is defined the same as CR, except absolute neutrophil count may be <1000/uL and/or platelet count may be ≤ 100,000/uL.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    MTD arm only, including eligible patients who received treatment and were evaluable for response
    Arm/Group Title CVP + Inotuzumab MTD
    Arm/Group Description Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 12
    Number [percentage of participants]
    83.33
    1666.6%
    3. Secondary Outcome
    Title Frequency and Severity of Toxicities
    Description Number of participants with Grade 3-5 adverse events that are possibly, probably or definitely related to study drug are reported by given type of adverse event.
    Time Frame Up to 3 years

    Outcome Measure Data

    Analysis Population Description
    Eligible participants who received at least one dose of protocol treatment.
    Arm/Group Title CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD
    Arm/Group Description Combination chemotherapy and inotuzumab ozogamicin - Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    Measure Participants 5 4 10 5 11 13
    Anemia
    2
    40%
    2
    50%
    7
    70%
    3
    60%
    5
    45.5%
    5
    38.5%
    Ascites
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    1
    7.7%
    Dysphagia
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    Encephalopathy
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    Enterocolitis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    0
    0%
    Fatigue
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    1
    7.7%
    Febrile neutropenia
    0
    0%
    2
    50%
    2
    20%
    3
    60%
    1
    9.1%
    7
    53.8%
    Fever
    1
    20%
    1
    25%
    1
    10%
    0
    0%
    0
    0%
    1
    7.7%
    Gastric hemorrhage
    2
    40%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Gastrointestinal disorders - Other, specify
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Headache
    0
    0%
    1
    25%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Hyperglycemia
    0
    0%
    0
    0%
    4
    40%
    4
    80%
    2
    18.2%
    0
    0%
    Hypertension
    0
    0%
    0
    0%
    1
    10%
    1
    20%
    0
    0%
    1
    7.7%
    Hypoalbuminemia
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    Hypocalcemia
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    Hypokalemia
    0
    0%
    0
    0%
    0
    0%
    1
    20%
    0
    0%
    0
    0%
    Infections and infestations - Other, specify
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    9.1%
    4
    30.8%
    Intracranial hemorrhage
    1
    20%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Lipase increased
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.7%
    Lung infection
    0
    0%
    0
    0%
    0
    0%
    2
    40%
    0
    0%
    0
    0%
    Lymphocyte count decreased
    2
    40%
    1
    25%
    3
    30%
    3
    60%
    6
    54.5%
    6
    46.2%
    Mucositis oral
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    1
    7.7%
    Neutrophil count decreased
    3
    60%
    3
    75%
    9
    90%
    4
    80%
    8
    72.7%
    8
    61.5%
    Platelet count decreased
    2
    40%
    2
    50%
    7
    70%
    4
    80%
    5
    45.5%
    10
    76.9%
    Renal and urinary disorders - Other, specify
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    1
    7.7%
    Sepsis
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    2
    15.4%
    Skin infection
    0
    0%
    0
    0%
    1
    10%
    0
    0%
    0
    0%
    0
    0%
    White blood cell decreased
    3
    60%
    4
    100%
    10
    100%
    5
    100%
    7
    63.6%
    9
    69.2%

    Adverse Events

    Time Frame Up to 3 years post registration
    Adverse Event Reporting Description All adverse events, regardless of attribution and grade, are reported.
    Arm/Group Title CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD
    Arm/Group Description Combination chemotherapy and inotuzumab ozogamicin � Dose level 1 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and 0.4 mg/m2 inotuzumab ozogamicin IV over 1 hour on days 1 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 2 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.6 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 3 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on day 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 4 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.4 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Dose level 5 Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Combination chemotherapy and inotuzumab ozogamicin - Maximum Tolerated Dose Patients receive cyclophosphamide IV on day 1, vincristine sulfate IV on day 1, prednisone PO on days 1-5, and inotuzumab ozogamicin IV over 1 hour at 0.8 mg/m2 on day 1 and 0.5 mg/m2 on days 8 and 15. Treatment repeats every 28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
    All Cause Mortality
    CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD
    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 4/5 (80%) 3/4 (75%) 9/10 (90%) 5/5 (100%) 9/11 (81.8%) 8/13 (61.5%)
    Serious Adverse Events
    CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD
    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 2/5 (40%) 2/4 (50%) 4/10 (40%) 1/5 (20%) 1/11 (9.1%) 11/13 (84.6%)
    Blood and lymphatic system disorders
    Anemia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Febrile neutropenia 0/5 (0%) 1/4 (25%) 1/10 (10%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Cardiac disorders
    Sinus tachycardia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Gastrointestinal disorders
    Ascites 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Gastric hemorrhage 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Gastrointestinal disorders-Other 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    General disorders
    Edema face 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Facial pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Fatigue 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 2/13 (15.4%)
    Fever 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Infections and infestations
    Infections and infestations-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 5/13 (38.5%)
    Lung infection 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Sinusitis 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Upper respiratory infection 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Investigations
    Investigations-Other 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Musculoskeletal and connective tissue disorders
    Neck pain 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Nervous system disorders
    Encephalopathy 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Headache 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Intracranial hemorrhage 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Nervous system disorders-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Seizure 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Syncope 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Renal and urinary disorders
    Renal and urinary disorders-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Respiratory, thoracic and mediastinal disorders
    Cough 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Dyspnea 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Hypoxia 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Vascular disorders
    Hematoma 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Hypotension 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Thromboembolic event 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Other (Not Including Serious) Adverse Events
    CVP + Inotuzumab Dose Level 1 CVP + Inotuzumab Dose Level 2 CVP + Inotuzumab Dose Level 3 CVP + Inotuzumab Dose Level 4 CVP + Inotuzumab Dose Level 5 CVP + Inotuzumab MTD
    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 5/5 (100%) 4/4 (100%) 10/10 (100%) 5/5 (100%) 11/11 (100%) 13/13 (100%)
    Blood and lymphatic system disorders
    Anemia 3/5 (60%) 3/4 (75%) 9/10 (90%) 5/5 (100%) 10/11 (90.9%) 9/13 (69.2%)
    Blood and lymphatic system disorders - Other 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Febrile neutropenia 0/5 (0%) 1/4 (25%) 2/10 (20%) 3/5 (60%) 2/11 (18.2%) 8/13 (61.5%)
    Lymph node pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Cardiac disorders
    Atrial fibrillation 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Cardiac disorders-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Palpitations 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Sinus bradycardia 2/5 (40%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Sinus tachycardia 1/5 (20%) 1/4 (25%) 6/10 (60%) 4/5 (80%) 4/11 (36.4%) 0/13 (0%)
    Ventricular tachycardia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders-Other 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Ear pain 1/5 (20%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Vertigo 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 2/13 (15.4%)
    Endocrine disorders
    Hypothyroidism 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Eye disorders
    Blurred vision 1/5 (20%) 1/4 (25%) 0/10 (0%) 2/5 (40%) 1/11 (9.1%) 2/13 (15.4%)
    Conjunctivitis 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Dry eye 2/5 (40%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Eye disorders-Other 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Eye pain 1/5 (20%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Photophobia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Watering eyes 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Gastrointestinal disorders
    Abdominal distension 0/5 (0%) 0/4 (0%) 0/10 (0%) 2/5 (40%) 0/11 (0%) 1/13 (7.7%)
    Abdominal pain 0/5 (0%) 1/4 (25%) 1/10 (10%) 1/5 (20%) 1/11 (9.1%) 7/13 (53.8%)
    Ascites 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Constipation 0/5 (0%) 0/4 (0%) 1/10 (10%) 2/5 (40%) 3/11 (27.3%) 5/13 (38.5%)
    Diarrhea 1/5 (20%) 2/4 (50%) 3/10 (30%) 1/5 (20%) 0/11 (0%) 4/13 (30.8%)
    Dry mouth 1/5 (20%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 1/11 (9.1%) 1/13 (7.7%)
    Dyspepsia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Dysphagia 0/5 (0%) 1/4 (25%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Enterocolitis 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Fecal incontinence 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Flatulence 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Gastric hemorrhage 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Gastrointestinal disorders-Other 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 4/13 (30.8%)
    Gingival pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Hemorrhoids 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Mucositis oral 1/5 (20%) 0/4 (0%) 1/10 (10%) 2/5 (40%) 1/11 (9.1%) 1/13 (7.7%)
    Nausea 1/5 (20%) 2/4 (50%) 5/10 (50%) 3/5 (60%) 2/11 (18.2%) 6/13 (46.2%)
    Oral hemorrhage 1/5 (20%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Oral pain 1/5 (20%) 0/4 (0%) 1/10 (10%) 2/5 (40%) 1/11 (9.1%) 1/13 (7.7%)
    Periodontal disease 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Stomach pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 2/13 (15.4%)
    Toothache 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 2/13 (15.4%)
    Vomiting 0/5 (0%) 0/4 (0%) 2/10 (20%) 1/5 (20%) 1/11 (9.1%) 3/13 (23.1%)
    General disorders
    Chills 1/5 (20%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 1/11 (9.1%) 8/13 (61.5%)
    Edema face 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Edema limbs 0/5 (0%) 1/4 (25%) 6/10 (60%) 3/5 (60%) 2/11 (18.2%) 4/13 (30.8%)
    Facial pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Fatigue 1/5 (20%) 2/4 (50%) 3/10 (30%) 1/5 (20%) 5/11 (45.5%) 5/13 (38.5%)
    Fever 3/5 (60%) 2/4 (50%) 2/10 (20%) 2/5 (40%) 1/11 (9.1%) 4/13 (30.8%)
    Flu like symptoms 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Gait disturbance 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 1/13 (7.7%)
    General disorders and admin site conditions - Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 4/13 (30.8%)
    Infusion related reaction 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Injection site reaction 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Localized edema 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Malaise 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Non-cardiac chest pain 0/5 (0%) 0/4 (0%) 1/10 (10%) 2/5 (40%) 1/11 (9.1%) 2/13 (15.4%)
    Pain 2/5 (40%) 1/4 (25%) 4/10 (40%) 1/5 (20%) 0/11 (0%) 1/13 (7.7%)
    Immune system disorders
    Allergic reaction 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Infections and infestations
    Catheter related infection 0/5 (0%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Enterocolitis infectious 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Infections and infestations-Other 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 5/13 (38.5%)
    Lung infection 0/5 (0%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 1/11 (9.1%) 0/13 (0%)
    Rash pustular 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Sepsis 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 4/13 (30.8%)
    Sinusitis 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Skin infection 0/5 (0%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Urinary tract infection 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Injury, poisoning and procedural complications
    Bruising 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 2/13 (15.4%)
    Fall 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Postoperative hemorrhage 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Investigations
    Activated partial thromboplastin time prolonged 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Alanine aminotransferase increased 2/5 (40%) 1/4 (25%) 2/10 (20%) 3/5 (60%) 5/11 (45.5%) 6/13 (46.2%)
    Alkaline phosphatase increased 3/5 (60%) 1/4 (25%) 4/10 (40%) 4/5 (80%) 7/11 (63.6%) 2/13 (15.4%)
    Aspartate aminotransferase increased 3/5 (60%) 3/4 (75%) 2/10 (20%) 3/5 (60%) 7/11 (63.6%) 2/13 (15.4%)
    Blood bilirubin increased 0/5 (0%) 2/4 (50%) 3/10 (30%) 1/5 (20%) 1/11 (9.1%) 5/13 (38.5%)
    Cholesterol high 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Creatinine increased 1/5 (20%) 0/4 (0%) 2/10 (20%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Fibrinogen decreased 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    INR increased 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Investigations-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Lipase increased 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Lymphocyte count decreased 2/5 (40%) 2/4 (50%) 3/10 (30%) 3/5 (60%) 7/11 (63.6%) 6/13 (46.2%)
    Neutrophil count decreased 3/5 (60%) 3/4 (75%) 9/10 (90%) 4/5 (80%) 10/11 (90.9%) 9/13 (69.2%)
    Platelet count decreased 3/5 (60%) 3/4 (75%) 8/10 (80%) 5/5 (100%) 10/11 (90.9%) 10/13 (76.9%)
    Weight gain 0/5 (0%) 1/4 (25%) 1/10 (10%) 1/5 (20%) 1/11 (9.1%) 1/13 (7.7%)
    Weight loss 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 1/13 (7.7%)
    White blood cell decreased 3/5 (60%) 4/4 (100%) 10/10 (100%) 5/5 (100%) 10/11 (90.9%) 10/13 (76.9%)
    Metabolism and nutrition disorders
    Acidosis 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Anorexia 1/5 (20%) 1/4 (25%) 3/10 (30%) 2/5 (40%) 1/11 (9.1%) 2/13 (15.4%)
    Dehydration 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 2/13 (15.4%)
    Hypercalcemia 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 1/11 (9.1%) 0/13 (0%)
    Hyperglycemia 4/5 (80%) 1/4 (25%) 5/10 (50%) 4/5 (80%) 7/11 (63.6%) 2/13 (15.4%)
    Hyperkalemia 1/5 (20%) 0/4 (0%) 2/10 (20%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Hypermagnesemia 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Hypernatremia 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 2/11 (18.2%) 2/13 (15.4%)
    Hypertriglyceridemia 0/5 (0%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 1/13 (7.7%)
    Hypoalbuminemia 1/5 (20%) 2/4 (50%) 6/10 (60%) 4/5 (80%) 9/11 (81.8%) 6/13 (46.2%)
    Hypocalcemia 1/5 (20%) 2/4 (50%) 4/10 (40%) 2/5 (40%) 3/11 (27.3%) 2/13 (15.4%)
    Hypoglycemia 0/5 (0%) 1/4 (25%) 1/10 (10%) 1/5 (20%) 3/11 (27.3%) 1/13 (7.7%)
    Hypokalemia 1/5 (20%) 3/4 (75%) 3/10 (30%) 3/5 (60%) 8/11 (72.7%) 3/13 (23.1%)
    Hypomagnesemia 2/5 (40%) 0/4 (0%) 2/10 (20%) 2/5 (40%) 3/11 (27.3%) 0/13 (0%)
    Hyponatremia 1/5 (20%) 1/4 (25%) 4/10 (40%) 3/5 (60%) 3/11 (27.3%) 2/13 (15.4%)
    Hypophosphatemia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 2/13 (15.4%)
    Metabolism and nutrition disorders - Other, specify 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Obesity 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Tumor lysis syndrome 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 0/5 (0%) 0/4 (0%) 0/10 (0%) 2/5 (40%) 1/11 (9.1%) 0/13 (0%)
    Arthritis 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Back pain 1/5 (20%) 1/4 (25%) 2/10 (20%) 2/5 (40%) 3/11 (27.3%) 3/13 (23.1%)
    Bone pain 0/5 (0%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 2/13 (15.4%)
    Chest wall pain 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Generalized muscle weakness 1/5 (20%) 0/4 (0%) 2/10 (20%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Joint range of motion decreased 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Muscle weakness lower limb 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 1/13 (7.7%)
    Muscle weakness right-sided 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Muscle weakness upper limb 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Musculoskeletal and connective tiss disorder - Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Myalgia 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 4/13 (30.8%)
    Neck pain 1/5 (20%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Pain in extremity 1/5 (20%) 1/4 (25%) 3/10 (30%) 2/5 (40%) 3/11 (27.3%) 4/13 (30.8%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Tumor pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Nervous system disorders
    Dizziness 1/5 (20%) 1/4 (25%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 3/13 (23.1%)
    Dysarthria 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Encephalopathy 1/5 (20%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Facial muscle weakness 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Headache 1/5 (20%) 1/4 (25%) 3/10 (30%) 3/5 (60%) 3/11 (27.3%) 7/13 (53.8%)
    Intracranial hemorrhage 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Lethargy 1/5 (20%) 1/4 (25%) 0/10 (0%) 2/5 (40%) 2/11 (18.2%) 2/13 (15.4%)
    Memory impairment 1/5 (20%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Nervous system disorders-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Paresthesia 2/5 (40%) 1/4 (25%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Peripheral motor neuropathy 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Peripheral sensory neuropathy 1/5 (20%) 0/4 (0%) 2/10 (20%) 3/5 (60%) 3/11 (27.3%) 6/13 (46.2%)
    Somnolence 1/5 (20%) 0/4 (0%) 0/10 (0%) 2/5 (40%) 1/11 (9.1%) 0/13 (0%)
    Tremor 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Psychiatric disorders
    Agitation 0/5 (0%) 1/4 (25%) 3/10 (30%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Anxiety 1/5 (20%) 0/4 (0%) 3/10 (30%) 1/5 (20%) 2/11 (18.2%) 0/13 (0%)
    Confusion 1/5 (20%) 1/4 (25%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 1/13 (7.7%)
    Delirium 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Depression 0/5 (0%) 0/4 (0%) 2/10 (20%) 2/5 (40%) 0/11 (0%) 0/13 (0%)
    Insomnia 0/5 (0%) 1/4 (25%) 1/10 (10%) 2/5 (40%) 3/11 (27.3%) 2/13 (15.4%)
    Personality change 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Psychiatric disorders-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Restlessness 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 1/11 (9.1%) 0/13 (0%)
    Renal and urinary disorders
    Acute kidney injury 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 2/13 (15.4%)
    Chronic kidney disease 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Hematuria 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Proteinuria 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 2/11 (18.2%) 1/13 (7.7%)
    Renal and urinary disorders-Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Urinary frequency 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Urinary incontinence 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 2/13 (15.4%)
    Urinary retention 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Urinary tract pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Urinary urgency 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Reproductive system and breast disorders
    Menorrhagia 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Penile pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Scrotal pain 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Vaginal hemorrhage 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Vaginal inflammation 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Respiratory, thoracic and mediastinal disorders
    Allergic rhinitis 0/5 (0%) 1/4 (25%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Atelectasis 1/5 (20%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Cough 1/5 (20%) 0/4 (0%) 3/10 (30%) 1/5 (20%) 2/11 (18.2%) 4/13 (30.8%)
    Dyspnea 0/5 (0%) 1/4 (25%) 2/10 (20%) 2/5 (40%) 2/11 (18.2%) 2/13 (15.4%)
    Epistaxis 0/5 (0%) 2/4 (50%) 0/10 (0%) 2/5 (40%) 1/11 (9.1%) 3/13 (23.1%)
    Hiccups 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Hoarseness 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Hypoxia 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Laryngeal hemorrhage 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Pleural effusion 0/5 (0%) 1/4 (25%) 1/10 (10%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Pneumonitis 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Postnasal drip 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Productive cough 0/5 (0%) 1/4 (25%) 1/10 (10%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Pulmonary edema 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Resp, thoracic and mediastinal disorders - Other 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Respiratory failure 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 1/13 (7.7%)
    Sore throat 0/5 (0%) 1/4 (25%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Skin and subcutaneous tissue disorders
    Alopecia 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 2/13 (15.4%)
    Bullous dermatitis 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Dry skin 0/5 (0%) 0/4 (0%) 3/10 (30%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Hyperhidrosis 1/5 (20%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 3/11 (27.3%) 0/13 (0%)
    Periorbital edema 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Pruritus 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 1/11 (9.1%) 0/13 (0%)
    Purpura 0/5 (0%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Rash maculo-papular 0/5 (0%) 1/4 (25%) 2/10 (20%) 2/5 (40%) 0/11 (0%) 2/13 (15.4%)
    Skin hyperpigmentation 0/5 (0%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Skin ulceration 1/5 (20%) 0/4 (0%) 1/10 (10%) 0/5 (0%) 0/11 (0%) 0/13 (0%)
    Vascular disorders
    Flushing 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)
    Hypertension 1/5 (20%) 1/4 (25%) 4/10 (40%) 3/5 (60%) 5/11 (45.5%) 3/13 (23.1%)
    Hypotension 1/5 (20%) 0/4 (0%) 1/10 (10%) 1/5 (20%) 0/11 (0%) 3/13 (23.1%)
    Lymphedema 0/5 (0%) 0/4 (0%) 0/10 (0%) 0/5 (0%) 0/11 (0%) 1/13 (7.7%)
    Thromboembolic event 0/5 (0%) 0/4 (0%) 0/10 (0%) 1/5 (20%) 0/11 (0%) 0/13 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.

    Results Point of Contact

    Name/Title SWOG Statistician
    Organization SWOG Statistics and Data Management Center
    Phone 2066674623
    Email amoseley@fredhutch.org
    Responsible Party:
    Southwest Oncology Group
    ClinicalTrials.gov Identifier:
    NCT01925131
    Other Study ID Numbers:
    • S1312
    • NCI-2013-01368
    • S1312
    • U10CA180888
    • U10CA032102
    First Posted:
    Aug 19, 2013
    Last Update Posted:
    Apr 6, 2022
    Last Verified:
    Apr 1, 2022