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