Autologous Stem Cell Transplant in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Giving two autologous stem cell transplants (one after the other) may be an effective treatment for Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well giving two autologous stem cell transplants works in treating patients with progressive or recurrent Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Primary Determine the 3-year progression-free survival of patients with progressive or recurrent Hodgkin's lymphoma treated with tandem autologous stem cell transplantation (2 courses of high-dose therapy with autologous stem cell rescue). Determine the response rate in patients treated with this regimen. Determine the toxic effects of this regimen in these patients. OUTLINE: This is a pilot study. Patients are stratified according to risk (poor risk [primary progressive, recurrent, or resistant relapse] vs good risk [first recurrence]). Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy. Autologous hematopoietic stem cell collection: Patients undergo autologous hematopoietic stem cell collection. Patients with an inadequate number of collected stem cells are removed from the study. First preparative regimen: Patients receive high-dose melphalan IV continuously over 16 hours on day -1. First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. They also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover. At least 4-8 weeks later, patients proceed to second preparative regimen. Second preparative regimen: Patients receive high-dose carmustine IV over 1-2 hours on days -6, -5, and -4, etoposide IV over 4 hours on day -3, and cyclophosphamide IV over 2 hours on day -2. Beginning 36-48 hours later, patients proceed to the second autologous SCT (day 0). Second autologous SCT: Patients undergo second autologous SCT on day 0. Patients also receive filgrastim (G-CSF) IV over 30 minutes once daily beginning on day 5 and continuing until blood counts recover. After completion of study treatment, patients are followed periodically. PROJECTED ACCRUAL: A total of 34 patients will be accrued for this study.

Official Title
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Tandem Autologous Stem Cell Transplantation for Patients With Primary Progressive or Poor Risk Recurrent Hodgkin's Disease

Conditions
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Lymphoma

Intervention / Treatment
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* Biological: filgrastim
* Drug: busulfan
* Drug: cyclophosphamide
* Drug: etoposide
* Drug: melphalan
* Procedure: autologous-autologous tandem hematopoietic stem cell transplantation
* Radiation: radiation therapy


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically* confirmed Hodgkin's lymphoma meeting ≥ 1 of the following criteria: Disease progression during initial first line chemotherapy Complete response lasting ≤ 90 days after induction Partial response lasting ≤ 90 days after induction First recurrence/progression with the duration of initial response ≤ 12 months after completion of chemotherapy NOTE: *There must be unequivocal radiological evidence of recurrent or progressive disease if biopsy was not obtained at time of disease recurrence/progression No clonal abnormalities in marrow collection Must have bilateral or unilateral bone marrow aspirates and biopsy within 42 days prior to stem cell collection Must have adequate sections of original diagnostic specimen available for review Needle aspirations or cytologies are not adequate No prior lymphoma, myelodysplastic syndromes, or leukemia (even if disease free ≥ 5 years) No CNS involvement PATIENT CHARACTERISTICS: Performance status Karnofsky 50-100% Life expectancy Not specified Hematopoietic Not specified Hepatic Bilirubin ≤ 1.5 times upper limit of normal* (ULN) NOTE: *Unless due to Hodgkin's lymphoma Renal Creatinine clearance ≥ 60 mL/min Creatinine ≤ 2.0 times ULN Cardiovascular Ejection fraction ≥ 45% by 2-D echocardiogram No significant active cardiac disease Pulmonary Adequate pulmonary function DLCO ≥ 45% Other Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer No known HIV or AIDS infection No active bacterial, fungal, or viral infection No medical condition that would preclude study treatment PRIOR CONCURRENT THERAPY: Chemotherapy See Disease Characteristics Surgery See Disease Characteristics

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Poor Risk<br>Primary progressive, recurrent, or resistant relapse patients | Biological: filgrastim<br>* 480 mcg beginning day +5<br>Drug: busulfan<br>* 11.2 mg/kg; 0.8 mg/kg IV q6h X 14 doses<br>Drug: cyclophosphamide<br>* 60 mg/kg IV over 2 hours x 2 days<br>Drug: etoposide<br>* 60 mg/kg, IV<br>Drug: melphalan<br>* 150mg/m2 in NS at a concentration of 0.4mg/cc infused over 60 minutes.<br>Procedure: autologous-autologous tandem hematopoietic stem cell transplantation<br>* autologous-autologous tandem hematopoietic stem cell transplantation<br>Radiation: radiation therapy<br>* radiation therapy<br>|
| Experimental: Good Risk<br>First recurrence patients | Biological: filgrastim<br>* 480 mcg beginning day +5<br>Drug: busulfan<br>* 11.2 mg/kg; 0.8 mg/kg IV q6h X 14 doses<br>Drug: cyclophosphamide<br>* 60 mg/kg IV over 2 hours x 2 days<br>Drug: etoposide<br>* 60 mg/kg, IV<br>Drug: melphalan<br>* 150mg/m2 in NS at a concentration of 0.4mg/cc infused over 60 minutes.<br>Procedure: autologous-autologous tandem hematopoietic stem cell transplantation<br>* autologous-autologous tandem hematopoietic stem cell transplantation<br>Radiation: radiation therapy<br>* radiation therapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression-free Survival | Outcome is based on the number of patients who were alive without progression or relapse within 1 year. Progression is defined as a 50% increase in the sum of products of all measurable lesions. | one year after second transplant | 
| Response Rate | Number of patients that receive a Complete Response (CR), Partial Response (PR)or Progression. CR defined as complete disappearance of all measurable and evaluable disease and no new lesions. PR is defined as >/= 50% decrease in the sum of products of all measurable lesions. Progression is defined as a 50% increase in the sum of products of all measurable lesions. | One year after second transplant | 
| Number of Patients That Experience Pulmonary Toxicity | Pulmonary toxicity are due to side effects that medicinal drugs cause to the lungs. | One year after second transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma, stage III adult Hodgkin lymphoma, stage IV adult Hodgkin lymphoma