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

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

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.

Study Overview

• Status: Terminated
• Conditions: Leukemia; Leukemia, Lymphocytic, Acute; Acute Lymphoid Leukemia (ALL)
• Intervention / Treatment: Drug: Human mAb 216; Drug: Vincristine

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Safety
Maximum tolerable dose without toxicity

Secondary Outcome Measures

Outcome Measure
Decrease in leukemic blasts

Collaborators and Investigators

• Sponsor: Clare Twist
• Collaborators: National Institutes of Health (NIH)
• Investigators: Principal Investigator: Clare J. Twist M.D., Stanford University

Study record dates

Study Major Dates

• Study Start: September 1, 2004
• Primary Completion (Actual): April 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: April 7, 2006
• First Submitted That Met QC Criteria: April 7, 2006
• First Posted (Estimate): April 11, 2006

Study Record Updates

• Last Update Posted (Estimate): June 3, 2016
• Last Update Submitted That Met QC Criteria: June 1, 2016
• Last Verified: November 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Leukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Vincristine
• Other Study ID Numbers: PEDSMAB216; 95343; CA85199-01; NCT00313053; 13822 (Other Identifier: Stanford IRB)