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