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Monoclonal Antibody (mAb) 216 With Chemotherapy in Adult Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia

Primary Purpose

Leukemia, Lymphocytic, Leukemia, Acute Lymphocytic Leukemia

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
MAb 216
Vincristine
Sponsored by
Steven E. Coutre
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Leukemia, Lymphocytic

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 3.1.1 Age Patients must be >= 18 years old at the time of study entry. 3.1.2 Diagnosis 3.1.2.1 Histologic Verification Patients must have had histologic verification of B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to traditional chemotherapy. 3.1.2.2 For patients WITHOUT prior allogeneic BMT: Second or subsequent bone marrow relapse Primary refractory marrow disease M3 marrow (>25% blasts) or >25% leukemic blasts in peripheral blood 3.1.2.3 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 VNTR confirmation 3.1.3 Confirmation of antibody reactivity 3.1.3.1 Patient's leukemic blasts (peripheral blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab) 3.1.3.2 Patient's RBC documented to NOT express fetal "i" antigen and RBC shown to NOT bind mAb 216 in vitro (Teng lab) 3.1.4 Patient Must Not Be Eligible For Therapies of Higher Priority 3.1.5 Performance Level (See Appendix I) Karnofsky >= 50% 3.1.6 Life Expectancy Must be at least 8 weeks. 3.1.7 Prior Therapy 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 received within one week of entry onto this study. Biologic, including monoclonal antibodies: At least 2 weeks since the completion of therapy with a biologic agent including monoclonal antibodies. Hydroxyurea can be used up to 72 hours before study entry 3.1.8 Organ Function Requirements 3.1.8.1 Bone Marrow Function: 3.1.8.1.1 No hematologic criteria for WBC, Hgb or platelets 3.1.8.1.2 Patients with thrombocytopenia should be responsive to platelet transfusions and must not have uncontrolled bleeding. 3.1.8.2 Adequate Renal Function Defined As: - A serum creatinine that is less than or equal to 2 x normal for age 3.1.8.3 Adequate Liver Function Defined As: Total bilirubin <= 2 x upper limit of normal (ULN) for age, and SGPT (ALT) <= 5 x upper limit of normal (ULN) for age 3.1.8.4 Adequate Cardiac Function Defined As: Shortening fraction of >= 27% by echocardiogram, or Ejection fraction of >= 50% by gated radionuclide study. 3.1.9 Regulatory 3.1.9.1 All patients must sign a written informed consent. 3.1.9.2 All institutional (IRB) and FDA requirements for human studies must be met. Exclusion Criteria: 3.2.1 CNS 3 or refractory CNS leukemia 3.2.2 Isolated extramedullary relapse 3.2.3 Uncontrolled infection 3.2.4 Lack of mAb 216 binding to patient's leukemic blasts in vitro 3.2.5 Binding of mAb 216 to the "i" antigen on patient's erythrocytes

Sites / Locations

  • Stanford University School of Medicine

Outcomes

Primary Outcome Measures

In this phase I study the endpoint is the determination of the maximum tolerable dose without toxicity.

Secondary Outcome Measures

A decrease in leukemic blasts. The study will be terminated if unacceptable doseSecondary endpoints are a decrease in leukemic blasts. The study will be terminated if unacceptable dose limiting toxicity is found. This is a phase I trial to study safety.

Full Information

First Posted
April 7, 2006
Last Updated
June 29, 2012
Sponsor
Steven E. Coutre
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1. Study Identification

Unique Protocol Identification Number
NCT00313079
Brief Title
Monoclonal Antibody (mAb) 216 With Chemotherapy in Adult Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia
Official Title
A Phase I Study of mAb 216 With Chemotherapy for the Treatment of Adult Patients With Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia
Study Type
Interventional

2. Study Status

Record Verification Date
June 2012
Overall Recruitment Status
Completed
Study Start Date
May 2006 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
July 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Steven E. Coutre

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A phase I trial in patients with relapsed or refractory leukemia of a human monoclonal antibody that kills B cell acute lymphoblastic leukemia. Trial will study 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, Leukemia, Acute Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
9 (Actual)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
MAb 216
Other Intervention Name(s)
Monoclonal Antibody 216
Intervention Description
Dosage: 1.25mg/kg intravenous with dose escalation
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin, leurocristine, VCR
Intervention Description
Dosage: 1.5mg/m2 intravenous weekly X 4
Primary Outcome Measure Information:
Title
In this phase I study the endpoint is the determination of the maximum tolerable dose without toxicity.
Secondary Outcome Measure Information:
Title
A decrease in leukemic blasts. The study will be terminated if unacceptable doseSecondary endpoints are a decrease in leukemic blasts. The study will be terminated if unacceptable dose limiting toxicity is found. This is a phase I trial to study safety.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 3.1.1 Age Patients must be >= 18 years old at the time of study entry. 3.1.2 Diagnosis 3.1.2.1 Histologic Verification Patients must have had histologic verification of B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to traditional chemotherapy. 3.1.2.2 For patients WITHOUT prior allogeneic BMT: Second or subsequent bone marrow relapse Primary refractory marrow disease M3 marrow (>25% blasts) or >25% leukemic blasts in peripheral blood 3.1.2.3 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 VNTR confirmation 3.1.3 Confirmation of antibody reactivity 3.1.3.1 Patient's leukemic blasts (peripheral blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab) 3.1.3.2 Patient's RBC documented to NOT express fetal "i" antigen and RBC shown to NOT bind mAb 216 in vitro (Teng lab) 3.1.4 Patient Must Not Be Eligible For Therapies of Higher Priority 3.1.5 Performance Level (See Appendix I) Karnofsky >= 50% 3.1.6 Life Expectancy Must be at least 8 weeks. 3.1.7 Prior Therapy 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 received within one week of entry onto this study. Biologic, including monoclonal antibodies: At least 2 weeks since the completion of therapy with a biologic agent including monoclonal antibodies. Hydroxyurea can be used up to 72 hours before study entry 3.1.8 Organ Function Requirements 3.1.8.1 Bone Marrow Function: 3.1.8.1.1 No hematologic criteria for WBC, Hgb or platelets 3.1.8.1.2 Patients with thrombocytopenia should be responsive to platelet transfusions and must not have uncontrolled bleeding. 3.1.8.2 Adequate Renal Function Defined As: - A serum creatinine that is less than or equal to 2 x normal for age 3.1.8.3 Adequate Liver Function Defined As: Total bilirubin <= 2 x upper limit of normal (ULN) for age, and SGPT (ALT) <= 5 x upper limit of normal (ULN) for age 3.1.8.4 Adequate Cardiac Function Defined As: Shortening fraction of >= 27% by echocardiogram, or Ejection fraction of >= 50% by gated radionuclide study. 3.1.9 Regulatory 3.1.9.1 All patients must sign a written informed consent. 3.1.9.2 All institutional (IRB) and FDA requirements for human studies must be met. Exclusion Criteria: 3.2.1 CNS 3 or refractory CNS leukemia 3.2.2 Isolated extramedullary relapse 3.2.3 Uncontrolled infection 3.2.4 Lack of mAb 216 binding to patient's leukemic blasts in vitro 3.2.5 Binding of mAb 216 to the "i" antigen on patient's erythrocytes
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nelson N Teng
Organizational Affiliation
Stanford University
Official's Role
Sub-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

Citations:
PubMed Identifier
21993685
Citation
Liedtke M, Twist CJ, Medeiros BC, Gotlib JR, Berube C, Bieber MM, Bhat NM, Teng NN, Coutre SE. Phase I trial of a novel human monoclonal antibody mAb216 in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. Haematologica. 2012 Jan;97(1):30-7. doi: 10.3324/haematol.2011.045997. Epub 2011 Oct 11.
Results Reference
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Monoclonal Antibody (mAb) 216 With Chemotherapy in Adult Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia

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