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

Clare Twist

Status and phase: Terminated; Phase 1

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

Treatments: Drug: Vincristine; Drug: Human mAb 216

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00313053

NCT00313053

CA85199-01

PEDSMAB216

13822 (Other Identifier)

95343

Details and patient eligibility

About

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.

Enrollment: 4 patients

Sex: All

Ages: 12 months to 18 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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 the"i" antigen on patient's erythrocytes

• Prior treatment with rituximab

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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4 participants in 1 patient group

Human mAb 216

Experimental group

Treatment:

Drug: Vincristine

Drug: Human mAb 216