Gemcitabine and Bendamustine in Patients With Relapsed or Refractory Hodgkin's Lymphoma

Study Overview
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Brief Summary
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This phase I/II trial studies the side effects and best dose of bendamustine hydrochloride when given together with gemcitabine hydrochloride and to see how well it works in treating patients with relapsed or refractory Hodgkin lymphoma. Drugs used in chemotherapy, such as gemcitabine hydrochloride and bendamustine hydrochloride, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving more than one drug, combination chemotherapy, may kill more cancer cells.

Detailed Description
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PRIMARY OBJECTIVES: I. To evaluate the toxicity and determine the maximum tolerated dose (MTD) of combined bendamustine (bendamustine hydrochloride) and gemcitabine (gemcitabine hydrochloride) in patients with relapsed or refractory Hodgkin's lymphoma. II. To determine the overall response rate of bendamustine and gemcitabine in patients with relapsed and refractory Hodgkin's lymphoma. SECONDARY OBJECTIVES: I. To determine whether therapy with bendamustine in the setting of relapsed or refractory Hodgkin's lymphoma will impact future stem cell collection. OUTLINE: This is a phase I, dose-escalation study of bendamustine hydrochloride followed by a phase II study. Patients receive gemcitabine hydrochloride intravenously (IV) over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3-6 months for 2 years, then every 6 months for up to 3 years.

Official Title
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A Phase I/II Study Of Gemcitabine And Bendamustine In Patients With Relapsed Or Refractory Hodgkin's Lymphoma

Conditions
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Adult Lymphocyte Depletion Hodgkin Lymphoma, Adult Lymphocyte Predominant Hodgkin Lymphoma, Adult Mixed Cellularity Hodgkin Lymphoma, Adult Nodular Lymphocyte Predominant Hodgkin Lymphoma, Adult Nodular Sclerosis Hodgkin Lymphoma, Recurrent Adult Hodgkin Lymphoma

Intervention / Treatment
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* Drug: gemcitabine hydrochloride
* Drug: bendamustine hydrochloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically documented Classical Hodgkin's lymphoma that is recurrent or refractory after standard chemotherapy; core biopsies are acceptable if they contain adequate tissue for primary diagnosis and immunophenotyping; bone marrow biopsies as the sole means of diagnosis are not acceptable Patients with Hodgkin's lymphoma may have one of the following World Health Organization subtypes: Nodular sclerosis Hodgkin's lymphoma Lymphocyte-rich Hodgkin's lymphoma Mixed cellularity Hodgkin's lymphoma Lymphocyte depletion Hodgkin's lymphoma Nodular lymphocyte predominant Hodgkin's lymphoma Patients must have relapsed or progressed after at least one prior therapy Patients with relapsed or refractory disease following stem cell transplantation are permitted No prior treatment with bendamustine; prior therapy with gemcitabine is permitted Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 Measurable disease must be present either on physical examination or imaging studies; non-measurable disease alone is not acceptable Measurable disease: lesions that can be accurately measured in at least two dimensions as >= 1.0 x 1.0 cm by computerized tomography (CT), PET/CT (positron emission tomography/CT), or magnetic resonance imaging (MRI) Non-measurable disease: all other lesions, including small lesions (less than 1.0 x 1.0 cm) and truly non-measurable lesions; lesions that are considered non-measurable include the following: Bone lesions (lesions if present should be noted) Ascites Pleural/pericardial effusion Lymphangitis cutis/pulmonis Bone marrow (involvement by Hodgkin's lymphoma should be noted) Non-pregnant and non-nursing; due to the teratogenic potential of these agents, pregnant or nursing patients may not be enrolled; women and men of reproductive potential should agree to use an effective means of birth control Patients with human immunodeficiency virus (HIV) infection are eligible; patients with HIV infection must meet the following: No evidence of co-infection with hepatitis B or C; cluster of differentiation (CD)4+ count >= 400/mm; no evidence of resistant strains of HIV; on anti-HIV therapy with an HIV viral load < 50 copies HIV ribonucleic acid (RNA)/mL; no history of acquired immune deficiency syndrome (AIDS) defining conditions Granulocytes >= 1000/μl Platelet count >= 75,000/μl Creatinine =< 20 mg/dL Bilirubin =< 2.0 mg/dL Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.0 x upper limits of normal

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: Treatment (combination chemotherapy)<br>Patients receive gemcitabine hydrochloride IV over 30 minutes on day 1 and bendamustine hydrochloride IV over 30 minutes on days 1 and 2. Treatment repeats every 21-28 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: gemcitabine hydrochloride<br>* Given IV<br>* Other names: Gemzar;Drug: bendamustine hydrochloride<br>* Given IV<br>* Other names: Treanda;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events in Terms of Dose-limiting Toxicity (DLT) and MTD of Bendamustine Hydrochloride (Phase I) | Dose limiting toxicity will be defined during cycle 1 only of the phase I trial. Hematologic and Infectious Dose Limiting Toxicities include: Grade 3 febrile neutropenia persisting> 7 days, Grade 4 infection or febrile neutropenia. Treatment delay>14 days due to grade 3-4 neutropenia or thrombocytopenia. Non-Hematological Dose Limiting Toxicities include: any Grade 3 or 4 non-hematologic toxicity related to study treatment with the exception of nausea or vomiting, alopecia, or electrolyte/glucose abnormalities that are correctable within 72 hours. | up to 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Response Rate (ORR) of Bendamustine Hydrochloride and Gemcitabine Hydrochloride in Patients With Relapsed or Refractory Hodgkin Lymphoma (Phase II) | Tested using Simon's two-stage Minimax design. Descriptive statistics (i.e. means, standard deviations, 95% confidence intervals for continuous variables, and frequencies for discrete data) and graphical analyses will be used for all correlative laboratory parameters. The associations between correlative laboratory parameters and clinical response will be evaluated using two sample t test or Fisher's exact test, whichever is appropriate. | up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hodgkin's Lymphoma, relapsed, refractory