S0410 Tandem Stem Cell Transplantation in Treating Patients With Progressive or Recurrent Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Radiation therapy uses high-energy x-rays to kill cancer cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving chemotherapy with a peripheral stem cell transplant may allow more chemotherapy to be given so that more cancer cells are killed. Tandem (two) autologous stem cell transplants may be an effective treatment for Hodgkin's lymphoma. PURPOSE: This phase II trial is studying how well tandem stem cell transplantation works in treating patients with progressive or recurrent Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Determine the 2-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 multicenter study. Salvage therapy (for patients with relapsed disease after achieving a previous complete response): Patients receive at least 2 courses of salvage chemotherapy or radiotherapy. No more than 6 weeks later, patients proceed to autologous hematopoietic stem cell collection. 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. Pre-transplant salvage radiation: Patients with residual tumor greater than 5 cm after initial salvage therapy undergo involved-field radiotherapy. All patients then proceed to the first preparative regimen. First preparative regimen: Patients receive high-dose melphalan IV on day -1. First autologous stem cell transplantation (SCT): Patients undergo autologous SCT on day 0. At least 28 days later, patients proceed to second preparative regimen. Second preparative regimen: Patients receive 1 of the following preparative regimens: Total-body irradiation (TBI)-based regimen: Patients undergo TBI twice daily on days -8 to -5. Patients also receive etoposide IV over 4 hours on day -4 and cyclophosphamide IV over 1 hour on day -2. Carmustine-based regimen: Patients receive carmustine IV over 2 hours on days -6 to -4, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2. Second autologous SCT: Patients undergo second autologous SCT on day 0. After completion of study treatment, patients are followed every 6 months for 2 years and then annually for up to 7 years. PROJECTED ACCRUAL: A total of 85 patients will be accrued for this study over 2 years.

Official Title
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Tandem Autologous Stem Cell Transplantation for Patients With Primary Progressive or Recurrent Hodgkin's Disease (A BMT Study), Phase II

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: carmustine
* 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 or cytologically confirmed Hodgkin's lymphoma Relapsed or refractory disease Biopsy or radiological evidence of disease at time of recurrence/progression required Has received ≥ 1 prior systemic chemotherapy regimen No clonal abnormalities in marrow collection Must undergo involved-field radiotherapy if bulky disease > 5 cm 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) Patients who relapse after achieving a complete remission must complete a minimum of 2 courses of salvage chemotherapy or radiation therapy to determine if sensitive or resistant recurrent disease is present No central nervous system (CNS) involvement PATIENT CHARACTERISTICS: Age 15 to 70 Performance status Zubrod 0-2 Life expectancy Not specified Hematopoietic Absolute neutrophil count ≥ 1,500/mm^3 Hepatic Bilirubin ≤ 1.5 times upper limit of normal (ULN) (unless due to Hodgkin's disease) Renal Creatinine clearance ≥ 60 mL/min Creatinine ≤ 2 times upper limit of normal Cardiovascular None of the following conditions requiring therapy: Coronary artery disease Cardiomyopathy Congestive heart failure Arrhythmias Ejection fraction ≥ 45% by Multi Gated Acquisition Scan (MUGA) or 2-D echocardiogram Pulmonary Adequate pulmonary function Corrected diffusing capacity of lung for carbon monoxide (DLCO) ≥ 60% OR Forced Expiratory Volume in One Side (FEV_1) ≥ 60% of predicted Other Not pregnant or nursing 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: Biologic therapy Not specified Chemotherapy See Disease Characteristics Endocrine therapy Not specified Radiotherapy See Disease Characteristics Surgery Not specified

Ages Eligible for Study
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Minimum Age: 15 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: High-dose therapy plus tandem transplant<br>Regimen consists of 2 cycles of high-dose therapy, each followed by stem cell infusion. Cycle 1 consists of high-dose melphalan followed by infusion of approximately 1.5 million cluster of differentiation 34 positive (CD34+) cells. Cycle 2 consists of either TBI-based or 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU)-based high-dose therapy followed by infusion of at least 2 million CD34+ cells. | Drug: carmustine<br>* 150 mg/m^2 IV over 2 hours 4, 5, and 6 days before transplant.<br>* Other names: BCNU;Drug: cyclophosphamide<br>* 100 mg/kg IV 2 days before transplant.<br>Drug: etoposide<br>* 60 mg/kg IV over 4 hours 4 days before transplant.<br>Drug: melphalan<br>* 150 mg/m^2 IV 1 day before transplant.<br>Procedure: autologous-autologous tandem hematopoietic stem cell transplantation<br>* 2.0 x 10^6 CD34+ cells, beginning at least 24 hours after melphalan infusion.<br>Radiation: radiation therapy<br>* 150 centigray (cGy) total body irradiation given b.i.d on days 5-8 before transplant.<br>* Other names: Total body irradiation (TBI);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 2-year Progression-free Survival | Measured from date of randomization to date of first observation of progressive disease, or death due to any cause | At day 60, then every 6 months for 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | Complete Response(CR) is a complete disappearance of all disease with the exception of nodes. No new lesions. previously enlarged organs must have regressed and not be palpable. Bone marrow(BM) must be negative if positive at baseline. Normalization of markers. CR Unconfirmed (CRU) does not qualify for CR above, due to a residual nodal mass or an indeterminate BM. Partial Response(PR) is a 50% decrease in the sum of products of greatest diameters (SPD) for up to 6 identified dominant lesions, including spleenic and hepatic nodules from baseline. No new lesions and no increase in the size of liver, spleen or other nodes. | At day 60, then every 6 months for 2 years | 
| Overall Survival | Measured from date of registration to date of death due to any cause or last contact | At day 60, then every 6 months for 2 years, then annually for a total of 7 years | 
| Number of Patients With Grade 3 Through Grade 5 Adverse Events That Are Related to Study Drug | Adverse Events (AEs) are reported by the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 3.0. For each patient, worst grade of each event type is reported. Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Fatal. | Assessed after cycle 1 high dose therapy, after cycle 2 high dose therapy, and at 1 month and 2 months after the second stem cell infusion | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent adult Hodgkin lymphoma