Aminocamptothecin in Treating Patients With Refractory or Recurrent Hodgkin's Disease or Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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Phase II trial to study the effectiveness of aminocamptothecin in treating patients who have refractory or recurrent Hodgkin's disease or non-Hodgkin's lymphoma. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die.

Detailed Description
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OBJECTIVES: I. Evaluate the response rate and duration of response to aminocamptothecin (9-AC) in patients with refractory or relapsed Hodgkin's disease or non-Hodgkin's lymphoma. II. Assess the toxicity of 9-AC in these patients. III. Validate a preliminary pharmacodynamic model relating total 9-AC concentration, albumin, and bilirubin to toxicity. IV. Determine whether 9-AC concentrations correlate with response. OUTLINE: Patients are stratified by disease histology (International Working Formulation (IWF) A-C vs IWF D-F) and center. Patients receive aminocamptothecin IV continuously on days 1-3. Treatment repeats every 2 weeks for a minimum of 3 courses in the absence of disease progression or unacceptable toxicity. Patients who achieve stable disease, partial response (PR), or complete response (CR) may receive 2 additional courses past best response (minimum of 6 courses if PR or CR). Patients are followed every 6 months for 2 years, and then annually thereafter.

Official Title
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PHASE II STUDY OF 9-AMINOCAMPTOTHECIN (9-AC/DMA, NSC# 603071) IN PREVIOUSLY TREATED HODGKIN'S DISEASE AND NON-HODGKIN'S LYMPHOMA: IWF GRADES A-H

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: aminocamptothecin


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically documented Hodgkin's disease (closed to accrual 4/15/2000) OR Histologically documented non-Hodgkin's lymphoma (NHL) of one of the following International Working Formulation (IWF) histologies: Small lymphocytic (absolute lymphocyte count less than 5,000) IWF A Follicular, predominantly small cleaved cell IWF B Follicular mixed IWF C Follicular large cell IWF D* Diffuse small cleaved cell IWF E* Diffuse mixed IWF F* Diffuse large cell IWF G* Large cell, immunoblastic IWF H* * Accrual of patients with these diagnoses closed 4/15/2000 Pathology review required within 60 days of registration Refractory to or relapsed after prior chemotherapy as follows: Low-grade NHL (IWF A-C): 1 or 2 prior therapies Intermediate-grade NHL (IWF D-H): 1 prior therapy (stratum closed 4/15/2000) Hodgkin's disease: 1 or 2 prior therapies (stratum closed 4/15/2000) Treatment with the same drugs on 2 different schedules considered 1 therapy Measurable disease by physical exam or imaging studies Mass larger than 1 x 1 cm Documented progression required of previously irradiated lesions The following are not considered measurable: Ascites or pleural effusion Bone marrow involvement Positive barium studies Bony disease (lytic lesions noted) No mantle cell or transformed lymphoma No parenchymal or leptomeningeal CNS disease A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of indolent or aggressive lymphoma will replace the former terminology of low, intermediate, or high grade lymphoma. However, this protocol uses the former terminology. PATIENT CHARACTERISTICS: Age: 18 and over Performance status: CALGB 0-2 Unless hypersplenism or biopsy-proven bone marrow involvement: Absolute granulocyte count at least 1,500/mm3 Platelet count at least 100,000/mm3 Bilirubin normal AST no greater than 4 times normal Creatinine normal No suspected HIV infection No second malignancy within past 5 years except: Curatively treated carcinoma of the cervix Curatively treated basal cell skin cancer No uncontrolled infection or other serious medical condition No psychiatric condition that precludes informed consent Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior allogeneic or autologous bone marrow transplant More than 3 weeks since chemotherapy (6 weeks since nitrosoureas, melphalan, or mitomycin) No prior camptothecin More than 3 weeks since radiotherapy

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: aminocamptothecin<br>aminocamptothecin | Drug: aminocamptothecin<br>* 850 micrograms/square meter/day (total dose 2550 micrograms/square meter) via central venous catheter using infusion pump over 72 hours + one cycle Cycle repeated every 14 days for minimum of 6 cycles if partial or complete response<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response |  | 2 years post treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Toxicity |  | day 1 of each cycle | 
| 9-AC/DMA concentrations |  | Pre-treatment cycle 1 and just prior to completion of cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Waldenstrom macroglobulinemia, recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent small lymphocytic lymphoma