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

Primary Purpose

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

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Human mAb 216
Vincristine
Sponsored by
Clare Twist
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic, Acute

Eligibility Criteria

12 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford University School of Medicine

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Human mAb 216

Arm Description

Outcomes

Primary Outcome Measures

Maximum tolerable dose without toxicity
Safety

Secondary Outcome Measures

Decrease in leukemic blasts

Full Information

First Posted
April 7, 2006
Last Updated
June 1, 2016
Sponsor
Clare Twist
Collaborators
National Institutes of Health (NIH)
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1. Study Identification

Unique Protocol Identification Number
NCT00313053
Brief Title
Study of mAb 216 With Chemotherapy for Treatment of Pediatric Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia
Official Title
A Phase I Study of mAb 216 With Chemotherapy for the Treatment of Pediatric Patients With Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
November 2012
Overall Recruitment Status
Terminated
Study Start Date
September 2004 (undefined)
Primary Completion Date
April 2008 (Actual)
Study Completion Date
July 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Clare Twist
Collaborators
National Institutes of Health (NIH)

4. Oversight

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Leukemia, Lymphocytic, Acute, Leukemia, Acute Lymphoid Leukemia (ALL)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Human mAb 216
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Human mAb 216
Intervention Description
Two treatment courses of mAb infusion will be given, with the same dose of antibody administered on Day 0 and on Day 7.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Intervention Description
Vincristine 1.5 mg/m2/dose (max dose = 2 mg) IVP on weekly x 4 doses (Days 7, 14, 21, 28)
Primary Outcome Measure Information:
Title
Maximum tolerable dose without toxicity
Title
Safety
Secondary Outcome Measure Information:
Title
Decrease in leukemic blasts

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clare J. Twist M.D.
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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