Study of mAb 216 With Chemotherapy for Treatment of Pediatric Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia

Study Overview
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Brief Summary
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This is a phase I trial in patients with relapsed or refractory leukemia of a human monoclonal antibody that kills B cell acute lymphoblastic leukemia. The trial will study the safety, pharmacokinetics, and anti-tumor activity of the antibody given as a single agent and with vincristine.

Official Title
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A Phase I Study of mAb 216 With Chemotherapy for the Treatment of Pediatric Patients With Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia

Conditions
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Leukemia, Lymphocytic, Acute, Leukemia, Acute Lymphoid Leukemia (ALL)

Intervention / Treatment
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* Drug: Human mAb 216
* Drug: Vincristine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria:- Patients must be > than 12 months at the time of study entry. Patients must have had histologic verification of B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to traditional chemotherapy. For patients WITHOUT prior allogeneic bone marrow transplant (BMT): Second or subsequent bone marrow relapse Primary refractory marrow disease M3 marrow (> 25% blasts) For patients WITH prior allogeneic BMT: First or subsequent bone marrow relapse post-BMT M3 marrow or M2 (> 5% and < 25% blasts) if cytogenetic or variable number tandem repeat (VNTR) confirmation Confirmation of antibody reactivity Patient's leukemic blasts (peripheral blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab). Patient's red blood cell (RBC) documented to NOT express fetal i antigen and RBC shown to NOT bind mAb 216 in vitro (Teng lab) Patient must not be eligible for therapies of higher priority Performance level Karnofsky 50% for patients > 10 years of age and Lansky >= 50 for patients <= 10 years of age. Life expectancy must be at least 8 weeks. Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study: Myelosuppressive chemotherapy: must not have been received within 2 weeks of entry onto this study. Biologic: at least 7 days since the completion of therapy with a biologic agent. No hematologic criteria for white blood cell (WBC), hemoglobin (Hgb), or platelets Patients with thrombocytopenia should be responsive to platelet transfusions and must not have uncontrolled bleeding. Adequate renal function defined as: a serum creatinine that is less than or equal to 1.5 x normal for age Adequate liver function defined as: total bilirubin <= 1.5 x upper limit of normal (ULN) for age, and SGPT (ALT) <= 5 x upper limit of normal (ULN) for age Adequate cardiac function defined as: shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study. All patients and/or their parents or legal guardians must sign a written informed consent/assent. All Institutional Review Board (IRB) and Food and Drug Administration (FDA) requirements for human studies must be met. Exclusion Criteria:- Central nervous system (CNS) 3 or refractory CNS leukemia Isolated extramedullary relapse Uncontrolled infection Lack of mAb 216 binding to patient's leukemic blasts in vitro Binding of mAb 216 to thei antigen on patient's erythrocytes Prior treatment with rituximab

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human mAb 216<br> | Drug: Human mAb 216<br>* Two treatment courses of mAb infusion will be given, with the same dose of antibody administered on Day 0 and on Day 7.<br>Drug: Vincristine<br>* Vincristine 1.5 mg/m2/dose (max dose = 2 mg) IVP on weekly x 4 doses (Days 7, 14, 21, 28)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerable dose without toxicity |  |  | 
| Safety |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decrease in leukemic blasts |  |  |