Non Hodgkin Lymphoma Clinical Trial
Immunotoxin in Treating Patients With Leukemia or Lymphoma
Summary
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.
Full Description
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.
Eligibility 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
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There is 1 Location for this study
Bethesda Maryland, 20892, United States
Bethesda Maryland, 20892, United States
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