Acute Lymphoid Leukemia (ALL), Leukemia, Leukemia, Lymphocytic, Acute
Conditions
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.
Interventions
DRUGHuman 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.
DRUGVincristine
Vincristine 1.5 mg/m2/dose (max dose = 2 mg) IVP on weekly x 4 doses (Days 7, 14, 21, 28)
Sponsors
National Institutes of Health (NIH)
Clare Twist
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 18 Years
Healthy volunteers
No
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 thei antigen on patient's erythrocytes * Prior treatment with rituximab
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Maximum tolerable dose without toxicity | — |
| Safety | — |
Secondary
| Measure | Time frame |
|---|---|
| Decrease in leukemic blasts | — |
Countries
United States
Outcome results
None listed