Combination Chemotherapy Followed by Peripheral Stem Cell Transplantation in Treating Children With Recurrent or Refractory Hodgkin's or Non-Hodgkin's Lymphoma

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Peripheral stem cell transplantation may allow doctors to give higher doses of chemotherapy and kill more cancer cells. PURPOSE: Phase II trial to study the effectiveness of combination chemotherapy followed by peripheral stem cell transplantation in treating children who have recurrent or refractory Hodgkin's lymphoma or non-Hodgkin's lymphoma.

Detailed Description
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OBJECTIVES: Estimate the failure-free survival rate in a cohort of relapsed Hodgkin's lymphoma and non-Hodgkin's lymphoma patients after retrieval therapy which includes peripheral blood stem cell transplantation (PBSCT) in patients who achieve a complete remission or partial remission. Estimate the post complete/partial remission failure-free survival rate in these patients. Characterize the time to recovery of normal bone marrow function after transplantation in these patients. OUTLINE: Patients receive 2 courses of reinduction chemotherapy followed by bone marrow biopsy and aspirate prior to peripheral blood stem cell (PBSC) harvest. If marrow involvement is still present at harvest, then 2 additional courses of induction chemotherapy are given. The PBSC transplantation preparative regimen should begin within 2 weeks of completing reinduction therapy course, consisting of the following: Carmustine IV over 3 hours on days -8, -7, and -6 Etoposide continuous IV over days -8, -7, and -6 Cyclophosphamide IV over 1 hour daily on days -5, -4, -3, and -2 Mesna as a 15 min infusion before each dose of cyclophosphamide then at 3, 6, 9, and 12 hours after initiation of each cyclophosphamide dose Methylprednisolone IV is given to protect lungs from the toxic effects of carmustine. PROJECTED ACCRUAL: A total of 30 patients will be accrued in each subgroup.

Official Title
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A Pilot Study of Peripheral Blood Stem Cell Transplantation (PBSCT) After Preparative Therapy Consisting of Cyclophosphamide, BCNU, and Etoposide (CBV) for Recurrent and Primarily Refractory Hodgkin's and Non-Hodgkin's Lymphoma

Conditions
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Lymphoma

Intervention / Treatment
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* Drug: carmustine
* Drug: cyclophosphamide
* Drug: etoposide
* Drug: mesna
* Procedure: peripheral blood stem cell transplantation


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically confirmed non-Hodgkin's lymphoma in first relapse or refractory after primary induction therapy Histologically confirmed Hodgkin's lymphoma in first relapse after chemotherapy with more than one nodal region involved at relapse or refractory after primary induction therapy (i.e., failed to achieve remission at the conclusion of standard induction chemotherapy) No prior radiotherapy only for low stage nodal disease No greater than 4 courses of standard chemotherapy for low stage nodal disease CSF or bone marrow involvement at time of study entry is allowed PATIENT CHARACTERISTICS: Age: 1 to 21 (at initial diagnosis) Performance status: Not specified Life expectancy: Not specified Hematopoietic: Not specified Hepatic: SGOT or SGPT less than 2.5 times normal Bilirubin no greater than 1.5 mg/dL Renal: Creatinine less than 1.5 mg/dL Glomerular filtration rate greater than 60 mL/min as measured by radionuclide scan or 24 hour urine collection for creatinine clearance Cardiovascular: Shortening fraction of at least 28% by echocardiogram Ejection fraction of at least 40% by radionuclide angiogram echocardiogram Pulmonary: Total lung capacity (TLC) at least 50% OR Vital capacity (VC) at least 65% of normal DLCO at least 55% of normal For children who are uncooperative to pulmonary function testing, no dyspnea at rest or with mild exercise, and a pulse oximetry of at least 95% Other: HIV negative 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: 1 Year
Maximum Age: 21 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: Reinduction Therapy<br>Two courses of reinduction chemotherapy followed by bone marrow biopsy and aspirate prior to peripheral blood stem cell (PBSC) harvest. If marrow involvement is still present at harvest, then 2 additional courses of induction chemotherapy are given. The PBSC transplantation preparative regimen should begin within 2 weeks of completing reinduction therapy course, consisting of the following: Carmustine IV over 3 hours on days -8, -7, and -6, Etoposide continuous IV over days -8, -7, and -6, Cyclophosphamide IV over 1 hour daily on days -5, -4, -3, and -2, Mesna as a 15 min infusion before each dose of cyclophosphamide then at 3, 6, 9, and 12 hours after initiation of each cyclophosphamide dose Methylprednisolone IV is given to protect lungs from the toxic effects of carmustine. | Drug: carmustine<br> <br> * Other names: NSC-409962;Drug: cyclophosphamide<br> <br> * Other names: NSC-26271;Drug: etoposide<br> <br> * Other names: NSC-141540;Drug: mesna<br> <br> * Other names: NSC-113891;Procedure: peripheral blood stem cell transplantation<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Failure-free survival rate | Estimate the failure-free survival rate and persistent grade 3 toxicity rate of PBSCT in recurrent HD and NHL patients and to perform interim safety monitoring based on these endpoints. |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimating parameters relevant to recovery of normal bone marrow function |  |  | 
| Predictive value of MRD assessment |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent childhood lymphoblastic lymphoma, childhood diffuse large cell lymphoma, childhood immunoblastic large cell lymphoma, recurrent/refractory childhood Hodgkin lymphoma, recurrent childhood small noncleaved cell lymphoma, recurrent childhood large cell lymphoma