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

Steven E. Coutre

Status and phase: Completed; Phase 1

Conditions: Acute Lymphocytic Leukemia; Leukemia, Lymphocytic; Leukemia

Treatments: Drug: Vincristine; Drug: MAb 216

Study type: Interventional

Funder types: Other

Identifiers

NCT00313079

HEMALL0003

96613 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 9 patients

Sex: All

Ages: 18+ years old

Volunteers: No 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:

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

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)