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