PHASE I STUDY OF ANTI-TAC(Fv)-PE38 (LMB-2), A RECOMBINANT SINGLE-CHAIN IMMUNOTOXIN FOR TREATMENT OF TAC-EXPRESSING MALIGNANCIES

Date de début de l'étude : 1 avril 1996

DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's disease, non-Hodgkin's lymphoma, or leukemia in one of the following categories: Adult T-cell leukemia or lymphoma (ATL) No smoldering ATL No limitation on prior therapy Cutaneous T-cell lymphoma (CTCL) Stages IB-III and failed at least 1 standard therapy Stage IV regardless of prior therapy Stages I-IV peripheral T-cell lymphoma Relapsed after standard chemotherapy Ineligible for or refused salvage chemotherapy or bone marrow transplantation (BMT) B-cell non-Hodgkin's lymphoma (NHL) of any histology Indolent stages II-IV NHL Failed at least 1 standard therapy Disease symptomatic and requiring treatment Aggressive NHL Relapsed after standard chemotherapy Ineligible for or refused salvage chemotherapy or BMT Chronic lymphocytic leukemia (CLL) Rai stages III and IV or Binet stage C Failed standard therapy and at least 1 salvage chemotherapy Primary B-cell prolymphocytic leukemia or prolymphocytic transformation of CLL Failed standard therapy and at least 1 salvage chemotherapy Hairy cell leukemia Failed standard and salvage chemotherapy Ineligible for or refused further salvage chemotherapy or BMT Acute myelogenous leukemia Failed standard chemotherapy Ineligible for or refused salvage chemotherapy or BMT Stages II-IV Hodgkin's disease Failed standard chemotherapy Ineligible for curative salvage radiotherapy or chemotherapy Ineligible for or refused BMT Patients with leukemias or lymphomas not easily classified in above categories who have failed standard therapy and are ineligible for or have refused bone marrow transplant Evidence of interleukin-2 receptor-alpha (IL2Ra) expression by one of the following: Greater than 10% of malignant cells reactive with anti-Tac by immunohistochemistry Greater than 10% of malignant cells from a particular site positive by FACS Greater than 400 IL2Ra sites per malignant cell by radiolabeled anti-Tac binding Soluble IL2Ra level greater than 1,000 U/mL (normal geometric mean 235, with 95% confidence levels of 112-502 U) Hodgkin's disease with measurable disease not amenable to biopsy No CNS disease requiring treatment Malignant cells in CSF allowed if judged not to represent clinically significant leukemic or lymphomatous meningitis (as in CSF contamination by blood) PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 50-100% Life expectancy: Greater than 2 months Hematopoietic: Absolute neutrophil count greater than 1,000/mm3* Platelet count greater than 50,000/mm3* NOTE: *nonleukemic patients Hepatic: AST and ALT less than 5 times normal Renal: Creatinine less than 2.0 mg/dL OR Creatinine clearance greater than 50 mL/min Pulmonary: FEV1, TLC, and DLCO greater than 50% of predicted if pulmonary or mediastinal involvement with tumor greater than one third of total thoracic diameter Other: HIV negative Not pregnant Fertile patients must use effective contraception Serum must neutralize no more than 75% LMB-2 in tissue culture PRIOR CONCURRENT THERAPY: Biologic therapy: See Disease Characteristics At least 3 weeks since prior interferon Chemotherapy: See Disease Characteristics At least 3 weeks since prior cytotoxic chemotherapy At least 3 weeks since prior retinoids No concurrent chemotherapy Endocrine therapy: No concurrent corticosteroids unless begun at least 3 weeks prior to entry and dose not increased during 3 weeks prior to entry Radiotherapy: See Disease Characteristics At least 3 weeks since prior whole-body electron beam radiotherapy Other radiotherapy allowed within 3 weeks of entry provided less than 10% of marrow irradiated and measurable disease exists outside radiation port Surgery: Not specified Other: See Disease Characteristics At least 3 weeks since any prior systemic therapy No other concurrent investigational agents