Rituximab, Gemcitabine, and Vinorelbine in Treating Patients With Hodgkin Lymphoma That Has Relapsed or Not Responded to Treatment

Study Overview
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Brief Summary
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RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cell-killing substances to them. Drugs used in chemotherapy, such as gemcitabine and vinorelbine, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving rituximab together with gemcitabine and vinorelbine may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with gemcitabine and vinorelbine works in treating patients with Hodgkin lymphoma that has relapsed or not responded to treatment.

Detailed Description
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OBJECTIVES: Primary Assess the response rate (complete response/remission, unconfirmed complete response, partial response/remission) in patients with relapsed or refractory Hodgkin lymphoma treated with 3 courses of rituximab, gemcitabine hydrochloride, and vinorelbine ditartrate. Secondary Assess progression-free survival, failure-free survival, and overall survival of patients treated with this regimen. Characterize the safety profile of this regimen in these patients. Determine the rate of adequate stem cell collection (≥ 2 million CD34+ cells) in patients eligible for stem cell transplantation. OUTLINE: Patients are assigned to 1 of 2 treatment groups according to eligibility for stem cell transplantation (SCT). Group 1 (eligible for SCT): Patients receive rituximab IV, vinorelbine ditartrate IV over 6-10 minutes, and gemcitabine hydrochloride IV over 30 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response (CR) or partial response (PR) undergo SCT. Group 2 (ineligible for SCT): Patients receive rituximab, vinorelbine ditartrate, gemcitabine hydrochloride, and pegfilgrastim as in group 1. Patients with CR, PR, or stable disease after 3 courses continue to receive therapy in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed for at least 2 years.

Official Title
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A Pilot Study of Rituximab-Gemcitabine-Navelbine for Relapsed/Refractory Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: rituximab
* Drug: gemcitabine hydrochloride
* Drug: vinorelbine ditartrate


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Pathologically confirmed classical Hodgkin lymphoma, including 1 of the following cell types: Nodular sclerosis Mixed cellularity Lymphocyte-rich Lymphocyte-depleted Measurable disease using the Cheson criteria, defined as ≥ 1 unidimensionally measurable lesion ≥ 2.0 cm by conventional techniques OR ≥ 1.0 cm by spiral CT scan Progressive or relapsed disease after ≥ 1 prior line of combination chemotherapy No known CNS metastasis PATIENT CHARACTERISTICS: ECOG performance status 0-1 ANC > 1,500/mm^3 Platelet count > 75,000/mm^3 Total bilirubin ≤ 2 mg/dL (unless due to hemolysis) AST or ALT ≤ 2.5 times upper limit of normal Creatinine normal OR creatinine clearance ≥ 50 mL/min Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No active hepatitis B infection No known chronic hepatitis B carrier No HIV positivity No concurrent uncontrolled illness including, but not limited to, any of the following: Symptomatic neurological illness Active uncontrolled systemic infection considered opportunistic, life-threatening, or clinically significant at the time of study treatment Symptomatic congestive heart failure Unstable angina pectoris Cardiac arrhythmia Significant pulmonary disease or hypoxia Psychiatric illness or social situation that would limit compliance with study requirements PRIOR CONCURRENT THERAPY: See Disease Characteristics More than 14 days since prior chemotherapy, immunotherapy, biological therapy, or investigational therapy and recovered No prior gemcitabine hydrochloride, vinorelbine ditartrate, or rituximab No other concurrent investigational or commercial agents or therapies with the intent to treat the malignancy

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group 1 (eligible for SCT)<br>Patients receive rituximab IV, vinorelbine ditartrate IV over 6-10 minutes, and gemcitabine hydrochloride IV over 30 minutes on day 1 and pegfilgrastim subcutaneously on day 2. Treatment repeats every 14 days for up to 3 courses in the absence of disease progression or unacceptable toxicity. Patients with complete response (CR) or partial response (PR) undergo SCT. | Biological: rituximab<br>* Given IV<br>Drug: gemcitabine hydrochloride<br>* Given IV<br>Drug: vinorelbine ditartrate<br>* Given IV<br>|
| Experimental: Group 2 (ineligible for SCT)<br>Patients receive rituximab, vinorelbine ditartrate, gemcitabine hydrochloride, and pegfilgrastim as in group 1. Patients with CR, PR, or stable disease after 3 courses continue to receive therapy in the absence of disease progression or unacceptable toxicity. | Biological: rituximab<br>* Given IV<br>Drug: gemcitabine hydrochloride<br>* Given IV<br>Drug: vinorelbine ditartrate<br>* Given IV<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response rate (complete response, unconfirmed complete response, partial response) |  | After first 3 cycles of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free survival, failure-free survival, and overall survival |  | Treatment start date to date of death for any reason | 
| Safety profile |  | Cycle 1 Day 1 through Follow-up | 
| Rate of adequate stem cell collection | This will be assessed only for patients eligible for stem-cell transplantation after completion of R-Gemzar/Navelbine therapy | After completion of 3 cycle of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma, adult lymphocyte depletion Hodgkin lymphoma, adult lymphocyte predominant Hodgkin lymphoma, adult mixed cellularity Hodgkin lymphoma, adult nodular sclerosis Hodgkin lymphoma