Gemcitabine and Hodgkin's Disease Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Hodgkin's Disease

Study Overview
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Brief Summary
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This is a phase 2 study of gemcitabine + high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue for Hodgkin's Disease

Detailed Description
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To assess the non-hematologic toxicity and determine the phase 2 dose of gemcitabine in combination with vinorelbine followed by carmustine, etoposide and cyclophosphamide and autologous hematopoietic stem cell transplantation [aka peripheral blood stem cell (PBSC)].

Official Title
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Gemcitabine and High-dose Chemotherapy Followed by Peripheral Blood Stem Cell Rescue for Relapsed or Resistant Hodgkin's Disease

Conditions
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Hodgkin Disease, Hodgkin's Lymphoma, Lymphoma

Intervention / Treatment
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* Drug: Gemcitabine
* Drug: Vinorelbine
* Drug: Carmustine
* Drug: Etoposide
* Drug: Cyclophosphamide
* Procedure: Autologous HCT


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically-proven recurrent or refractory Hodgkin's Disease (Hodgkin's lymphoma) on the basis of excisional biopsy whenever possible. Age < 70 years Eastern Cooperative Oncology Group (ECOG) performance status 0 to 3. Phase 1 study component only: 1 or more of the following adverse risk factors Stage IV extranodal disease at relapse B symptoms Failure to achieve minimal disease with most recent chemotherapy (single lymph nodes < 2 cm or >75% reduction in a bulky tumor mass and bone marrow involvement < 10%) Progression during induction or salvage therapy Phase 2 study component only: No risk factor criteria Computerized tomography (CT) scan of the chest, abdomen and pelvis, with assessment of response to last chemotherapy, within 4 weeks of registration. Gallium scan or positron emission tomography (PET) scan confirmation of disease within 4 weeks of registration is highly recommended Bone marrow biopsy and cytogenetic analysis within 8 weeks of registration Women of child-bearing potential and sexually active males expected to use an accepted and effective method of birth control Pretreatment serum bilirubin < 2 x the institutional upper limit of normal (ULN) (within 28 days prior to registration) Serum creatinine < 2 x the institutional ULN (within 28 days prior to registration) Measured or estimated creatinine clearance > 60 cc/min by the following formula (within 28 days prior to registration): Estimated Creatinine Clearance = (140 age) x WT(kg) x 0.85 (if female) x creatinine (mg/dL) Electrocardiogram (ECG) demonstrating no significant abnormalities suggestive of active cardiac disease (within 42 days prior to registration) Patients over age 50, who have received chest irradiation or a total of 300 mg/m2 of doxorubicin or with any history of cardiac disease must have a radionuclide ejection fraction (within 42 days prior to registration). If the ejection fraction is 40 to 50%, the patient will have a cardiology consult Corrected diffusion capacity > 55% Written informed consent in accordance with institutional and federal guidelines Exclusion Criteria: Positive HIV antibody test (must be conducted within 42 days of registration) No chemotherapy other than corticosteroids should be administered within 2 weeks of the initiation of protocol therapy Pregnant Breast-feeding Requiring therapy for: Coronary artery disease Cardiomyopathy Dysrhythmia, or Congestive heart failure Over age 50 and has received chest irradiation or a total of 300 mg/m^2 of doxorubicin History of cardiac disease and the ejection fraction is < 40% (radionuclide ejection fraction must be within 42 days of registration) Known allergy to etoposide History of Grade 3 hemorrhagic cystitis with cyclophosphamide History of grade 2 or greater sensory or motor peripheral neuropathy due to prior vinca alkaloid use No prior malignancy (EXCEPTION: adequately treated basal cell or squamous cell skin cancer; in situ cervical cancer; or other cancer for which the patients has been disease-free for 5 years). Patients with a prior diagnosis of non-Hodgkin's lymphoma are not eligible.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Gemcitabine + Autologous HCT<br>Gemcitabine and high-dose chemotherapy followed by peripheral blood stem cell (PBSC) rescue. Chemotherapy includes Gemcitabine + Vinorelbine + Carmustine + Etoposide + Cyclophosphamide. | Drug: Gemcitabine<br> <br> * Other names: Gemzar;Drug: Vinorelbine<br> <br> * Other names: Navelbine;Drug: Carmustine<br> <br> * Other names: BCNU;Drug: Etoposide<br> <br> * Other names: Vepesid;Drug: Cyclophosphamide<br> <br> * Other names: Neosar;Procedure: Autologous HCT<br> <br> * Other names: Peripheral blood stem cell (PBSC) rescue;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting Toxicity of Gemcitabine Due to Non-hematologic Toxicity | Reported as the number of Phase 1 participants by gemcitabine dose that experienced non-hematologic toxicity, ie, drug-related adverse events. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pulmonary Toxicity (BCNU Pneumonitis) | Pulmonary toxicity as assessed by the number of participants that experience BCNU pneumonitis, ie, pneumonitis due to carmustine (BCNU). | 2 years | 
| Overall Survival (OS) | Reports the percentage of participants surviving 6 months after PBSC infusion (transplant). | 2 years | 
| Relapse Post-transplant | Reports the percentage of participants that experienced relapse post-transplant. | 2 years | 
| Survival Measures | Reports the survival measures: Freedom from progression (FFP) Event-free survival (EFS) Overall survival (OS) EFS and OS were estimated by Kaplan-Meier method Progression was defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions | 2 years |