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.
18.104.22.168 Histologic Verification Patients must have had histologic verification of
B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to
22.214.171.124 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
126.96.36.199 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 188.8.131.52 Patient's leukemic blasts (peripheral
blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab) 184.108.40.206
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
220.127.116.11 Bone Marrow Function: 18.104.22.168.1 No hematologic criteria for WBC, Hgb or platelets
22.214.171.124.2 Patients with thrombocytopenia should be responsive to platelet transfusions and
must not have uncontrolled bleeding.
126.96.36.199 Adequate Renal Function Defined As:
- A serum creatinine that is less than or equal to 2 x normal for age
188.8.131.52 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
184.108.40.206 Adequate Cardiac Function Defined As:
- Shortening fraction of >= 27% by echocardiogram, or
- Ejection fraction of >= 50% by gated radionuclide study.
220.127.116.11 All patients must sign a written informed consent. 18.104.22.168 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