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

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

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.

Study Overview

• Status: Completed
• Conditions: Leukemia; Acute Lymphocytic Leukemia; Leukemia, Lymphocytic
• Intervention / Treatment: Drug: MAb 216; Drug: Vincristine

• Study Type: Interventional
• Enrollment (Actual): 9
• 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: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

1. Second or subsequent bone marrow relapse
2. Primary refractory marrow disease
3. M3 marrow (>25% blasts) or >25% leukemic blasts in peripheral blood

3.1.2.3 For patients WITH prior allogeneic BMT:

1. First or subsequent bone marrow relapse post-BMT
2. 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.

1. Myelosuppressive chemotherapy: Must not have received within one week of entry onto this study.
2. Biologic, including monoclonal antibodies: At least 2 weeks since the completion of therapy with a biologic agent including monoclonal antibodies.
3. 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
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.

Collaborators and Investigators

• Sponsor: Steven E. Coutre
• Investigators: Sub-Investigator: Nelson N Teng, Stanford University

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: May 1, 2006
• Primary Completion (Actual): February 1, 2009
• Study Completion (Actual): July 1, 2009

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): July 3, 2012
• Last Update Submitted That Met QC Criteria: June 29, 2012
• Last Verified: June 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: HEMALL0003; 96613 (Other Identifier: Stanford University alternate IRB Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No