Monoclonal Antibody Therapy, Paclitaxel, and Cyclosporine in Treating Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Combining monoclonal antibody therapy with cyclosporine and paclitaxel may be an effective treatment for non-Hodgkin's lymphoma. PURPOSE: Phase I trial to study the effectiveness of radiolabeled monoclonal antibody therapy combined with paclitaxel and cyclosporine in treating patients who have recurrent or refractory non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose of yttrium Y 90 monoclonal antibody Lym-1 in combination with paclitaxel and cyclosporine in patients with recurrent or refractory non-Hodgkin's lymphoma. OUTLINE: This is a dose-escalation study of yttrium Y 90 monoclonal antibody Lym-1 (Y90 MOAB Lym-1). Patients receive oral cyclosporine every 12 hours on days -2 to 14. Patients receive unlabeled MOAB Lym-1 IV followed by a tracer dose of indium In 111 MOAB Lym-1 IV on day 0. On day 7, patients receive unlabeled MOAB Lym-1 IV followed by Y90 MOAB Lym-1 IV. Patients in cohorts 2-4 also receive paclitaxel IV over 3 hours on day 9. Courses repeat every 8 weeks for a total of 3 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3 patients receive escalating doses of Y90 MOAB Lym-1 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 patients experience dose-limiting toxicity. Patients are followed monthly for 3 months, every 3 months for 21 months, and then every 6 months for 3 years. PROJECTED ACCRUAL: A total of 24 patients will be accrued for this study within 36 months.

Official Title
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Combined Modality Radioimmunotherapy For Non-Hodgkin's Lymphoma With Three Cycles Of 90Y-DOTA-peptide-Lym-1, Paclitaxel and Cyclosporin A

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: monoclonal antibody Lym-1
* Drug: cyclosporine
* Drug: paclitaxel
* Radiation: indium In 111 monoclonal antibody Lym-1
* Radiation: yttrium Y 90 monoclonal antibody Lym-1


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Diagnosis of non-Hodgkin's lymphoma (NHL) that has failed standard first-line chemotherapy Measurable disease NHL tissue Lym-1 reactive in vitro Normocellular bone marrow as evidenced by less than 25% of the bone marrow being NHL by bilateral bone marrow biopsy No bone marrow evidence of myelodysplastic syndrome HAMA titer negative PATIENT CHARACTERISTICS: Age: 18 and over Performance status: Karnofsky 70-100% Life expectancy: 3 to 6 months Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 130,000/mm^3 Hepatic: Bilirubin no greater than 1.5 mg/dL AST no greater than 84 U/L Renal: Creatinine less than 1.5 mg/dL OR Creatinine clearance at least 50 mL/min Cardiovascular: LVEF at least 50% Pulmonary: FEV1 at least 60% of predicted FVC at least 60% of predicted DLCO at least 50% Other: No other prior malignancy within the past 5 years except for nonmelanoma skin cancer HIV negative Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: Biologic therapy: Not specified Chemotherapy: See Disease Characteristics At least 4 weeks since prior chemotherapy Endocrine therapy: Not specified Radiotherapy: At least 4 weeks since prior external beam radiotherapy Surgery: Not specified

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: monoclonal antibody Lym-1|nan|
|Drug: cyclosporine|nan|
|Drug: paclitaxel|nan|
|Radiation: indium In 111 monoclonal antibody Lym-1|nan|
|Radiation: yttrium Y 90 monoclonal antibody Lym-1|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 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, recurrent mantle cell lymphoma, recurrent marginal zone lymphoma, recurrent small lymphocytic lymphoma, extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue, nodal marginal zone B-cell lymphoma, splenic marginal zone lymphoma