A Phase I Study of mAb 216 With Chemotherapy for the Treatment of Adult Patients With Relapsed or Refractory B-Lineage Acute Lymphoblastic Leukemia
3.1.1 Age Patients must be >= 18 years old at the time of study entry.
220.127.116.11 Histologic Verification Patients must have had histologic verification of
B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to
18.104.22.168 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
22.214.171.124 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 126.96.36.199 Patient's leukemic blasts (peripheral
blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab) 188.8.131.52
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
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
184.108.40.206 Bone Marrow Function: 220.127.116.11.1 No hematologic criteria for WBC, Hgb or platelets
18.104.22.168.2 Patients with thrombocytopenia should be responsive to platelet transfusions and
must not have uncontrolled bleeding.
22.214.171.124 Adequate Renal Function Defined As:
- A serum creatinine that is less than or equal to 2 x normal for age
126.96.36.199 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
188.8.131.52 Adequate Cardiac Function Defined As:
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by gated radionuclide study.
184.108.40.206 All patients must sign a written informed consent. 220.127.116.11 All institutional (IRB)
and FDA requirements for human studies must be met.
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