Immunotoxin in Treating Patients With Leukemia or Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Immunotoxins can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. PURPOSE: Phase I trial to study the effectiveness of LMB-2 immunotoxin in treating patients who have leukemia or lymphoma.

Detailed Description
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OBJECTIVES: Assess the therapeutic efficacy and toxicity of the recombinant immunotoxin LMB-2, an anti-Tac murine monoclonal antibody fragment conjugated to a truncated portion of Pseudomonas exotoxin, in patients with Tac-expressing leukemias and lymphomas. Define the pharmacokinetics of LMB-2, including the terminal elimination serum half-life, area under the curve, and volume of distribution. Evaluate, in a preliminary manner, the immunogenicity of LMB-2 in these patients. Determine the effect of LMB-2 on various components of the circulating cellular immune system. OUTLINE: This is a dose escalation study. Patients receive LMB-2 immunotoxin IV over 30 minutes on days 1, 3, and 5. Treatment repeats every 15-21 days for up to 10 courses in the absence of disease progression, neutralizing antibodies, or unacceptable toxicity. Cohorts of 3-6 patients each receive escalating doses of LMB-2 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 patient experiences dose limiting toxicity. PROJECTED ACCRUAL: A maximum of 40 patients will be accrued for this study.

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

Conditions
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Leukemia, Lymphoma

Intervention / Treatment
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* Biological: LMB-2 immunotoxin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment


Arms and Interventions

| Intervention/Treatment |
| --- |
|Biological: LMB-2 immunotoxin|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma, stage IV cutaneous T-cell non-Hodgkin lymphoma, recurrent cutaneous T-cell non-Hodgkin lymphoma, Waldenström macroglobulinemia, recurrent adult acute myeloid leukemia, recurrent adult acute lymphoblastic leukemia, relapsing chronic myelogenous leukemia, refractory chronic lymphocytic leukemia, refractory hairy cell leukemia, recurrent small lymphocytic lymphoma, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma, recurrent adult diffuse small cleaved cell lymphoma, recurrent adult diffuse mixed cell lymphoma, recurrent adult diffuse large cell lymphoma, recurrent adult immunoblastic large cell lymphoma, recurrent adult lymphoblastic lymphoma, recurrent adult Burkitt lymphoma, stage I adult T-cell leukemia/lymphoma, stage II adult T-cell leukemia/lymphoma, stage III adult T-cell leukemia/lymphoma, stage IV adult T-cell leukemia/lymphoma, recurrent adult T-cell leukemia/lymphoma, prolymphocytic leukemia, recurrent mantle cell lymphoma, stage IV mycosis fungoides/Sezary syndrome, recurrent mycosis fungoides/Sezary syndrome, recurrent marginal zone lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma