Combination Chemotherapy in Treating Patients With Relapsed or Refractory Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: Phase I/II trial to study the effectiveness of combination chemotherapy in treating patients who have relapsed or refractory Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the maximum tolerated dose and toxicity of gemcitabine, vinorelbine, and doxorubicin HCl liposome in patients with relapsed or refractory Hodgkin's lymphoma. Determine the complete and partial response rates of patients treated with this regimen. OUTLINE: This is a dose-escalation, multicenter study. Phase I: Patients receive vinorelbine IV over 6-10 minutes, gemcitabine IV over 30 minutes, and doxorubicin HCl liposome IV over 30-60 minutes on days 1 and 8. Treatment continues every 21 days for 2-6 courses in the absence of unacceptable toxicity or disease progression. Patients who respond to treatment after 2 or more courses may stop protocol therapy to undergo peripheral blood stem cell transplantation. Cohorts of 3-6 patients receive escalating doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Once the MTD is determined, additional patients are accrued to receive treatment with gemcitabine, vinorelbine, and doxorubicin HCl liposome at the recommended phase II dose. Phase II: Patients are assigned to 1 of 2 treatment groups. Group 1: Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome as in phase I. Group 2: Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome as in group 1. Patients are followed every 6 months for 2 years and then annually for 6 years. PROJECTED ACCRUAL: Approximately 3-100 patients (3-42 for phase I and 20-58 for phase II [29 per group]) will be accrued for this study within 3 years.

Official Title
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A Phase I/II Study of Gemcitabine (GEMZAR)/Vinorelbine (NAVELBINE)/Liposomal Doxorubicin (DOXIL) in Relapsed/Refractory Hodgkin's Disease

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: pegylated liposomal doxorubicin hydrochloride
* Drug: vinorelbine tartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy Core biopsy is acceptable if adequate tissue is obtained for primary diagnosis and immunophenotyping Bone marrow biopsy is not acceptable as sole means of diagnosis Measurable disease Tumor mass greater than 1 cm PATIENT CHARACTERISTICS: Age: Any age Hematopoietic: Absolute neutrophil count at least 1,500/mm^3 Platelet count at least 100,000/mm^3 Hepatic: Bilirubin no greater than 2.0 mg/dL unless history of Gilbert's disease AST no greater than 2 times upper limit of normal Renal: Creatinine no greater than 2.0 mg/dL Cardiovascular: LVEF at least 45% by MUGA (for patients whose lifetime cumulative doxorubicin dose exceeds 400 mg/m^2) Other: Not pregnant or nursing Fertile patients must use effective contraception PRIOR CONCURRENT THERAPY: No prior gemcitabine, vinorelbine, or doxorubicin HCl liposome No other concurrent chemotherapy Endocrine therapy: No concurrent hormones except for nondisease-related conditions (e.g., insulin for diabetes) or steroids for adrenal failure No concurrent dexamethasone or other steroidal antiemetics
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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: vinorelbine + gemcitabine + doxorubicin - higher doses<br>Patients who have not undergone prior transplantation receive vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years. | Drug: gemcitabine hydrochloride<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vinorelbine tartrate<br> <br> |
| Experimental: vinorelbine + gemcitabine + doxorubicin - lower doses<br>Patients who have undergone prior transplantation receive lower doses of vinorelbine, gemcitabine, and doxorubicin HCl liposome. Patients are followed every 6 months for 2 years and then annually for 6 years. | Drug: gemcitabine hydrochloride<br> <br> Drug: pegylated liposomal doxorubicin hydrochloride<br> <br> Drug: vinorelbine tartrate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response rate |  | Up to 4 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall survival |  | Up to 4 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma, recurrent/refractory childhood Hodgkin lymphoma