Combination Chemotherapy Plus Radiation Therapy Followed by Peripheral Stem Cell Transplantation in Treating Patients With Non-Hodgkin's Lymphoma

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00002697
Recruitment Status : Completed
First Posted : January 27, 2003
Last Update Posted : July 3, 2013
Information provided by:
Memorial Sloan Kettering Cancer Center

Brief Summary:

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining chemotherapy with radiation therapy and peripheral stem cell transplantation may kill more tumor cells.

PURPOSE: Phase II trial to study the effectiveness of high-dose combination chemotherapy plus radiation therapy followed by peripheral stem cell transplantation in patients with refractory or recurrent non-Hodgkin's lymphoma.

Condition or disease Intervention/treatment Phase
Lymphoma Biological: filgrastim Biological: sargramostim Drug: carboplatin Drug: etoposide Drug: ifosfamide Procedure: autologous bone marrow transplantation Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy Phase 2

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Detailed Description:


  • Determine the efficacy of mobilization using filgrastim (G-CSF) with or without standard-dose ifosfamide, carboplatin, and etoposide (ICE), conditioning using ifosfamide and etoposide plus total body irradiation or high-dose ICE, and autologous peripheral blood stem cell (PBSC) transplantation as salvage therapy in patients with refractory, recurrent, or poor prognosis non-Hodgkin's lymphoma.
  • Determine the efficacy of reinduction comprising ICE followed by autologous PBSC transplantation in these patients.
  • Determine the ability of standard-dose ICE combined with hematopoietic growth factors to mobilize PBSC in these patients.
  • Determine the contamination of PBSC by lymphoma cells in patients treated with this mobilization regimen.
  • Determine the quality of life of patients treated with this regimen.

OUTLINE: Patients are stratified according to disease status (relapsed vs refractory), lymphoma grade (low vs intermediate vs high), number of extranodal sites, serum lactic dehydrogenase, performance status, age, and volume of disease.

  • Mobilization/harvest: Patients in first or greater complete remission (CR) are treated on regimen A, whereas patients with recurrent or refractory disease are treated on regimen B.

    • Regimen A: Patients with poor prognosis intermediate-grade lymphoma (IGL) in first CR or IGL or low-grade lymphoma (LGL) in second or greater CR receive mobilization with filgrastim (G-CSF) subcutaneously (SC) daily on days 1-7. Autologous peripheral blood stem cells (PBSC) are harvested and selected for CD34+ cells on days 5 and 6 (and day 7 if needed).
    • Regimen B: Patients who are currently on the MSKCC standard dose salvage therapy protocol with ifosfamide, carboplatin, and etoposide (ICE) for recurrent or refractory IGL receive additional mobilization with G-CSF after completion of the last course of ICE. Patients with recurrent or refractory IGL, immunoblastic lymphoma, or LGL who have not previously received ifosfamide and are not currently on the MSKCC standard dose salvage protocol with ICE receive ifosfamide IV and carboplatin on day 2 and etoposide IV on days 1-3 (standard-dose ICE) followed by G-CSF SC. When blood counts recover, autologous PBSC are harvested and selected for CD34+ cells.
    • Regimens A and B: If additional hematopoietic growth factors (HGFs) become available, they may be administered concurrently with G-CSF. If inadequate CD34+ cells are collected, then autologous bone marrow is harvested.
  • Conditioning: Patients who are under age 60 and have not received dose-limiting radiotherapy are treated on regimen C. Patients who are age 60 and over and patients who are under age 60 and have received dose-limiting radiotherapy are treated on regimen D.

    • Regimen C: Patients undergo hyperfractionated total body irradiation twice a day on days -10 to -7 and ifosfamide IV over 1 hour followed by etoposide IV over 23 hours on days -6 to -2.
    • Regimen D: Patients receive ifosfamide IV over 1 hour, followed by etoposide IV over 11 hours, followed by carboplatin IV over 1 hour, followed by etoposide IV over 11 hours on days -7 to -3 (high-dose ICE).
    • Regimens C and D: Patients with residual or relapsed disease may undergo boost radiotherapy twice a day, 5 days a week, for 1-2 weeks before conditioning or after transplantation.
  • Transplantation: PBSC or bone marrow is reinfused on day 0. Patients receive G-CSF SC every 12 hours beginning on day 1 and continuing until blood counts recover. If additional HGFs become available, they may be administered concurrently with G-CSF.

Quality of life is assessed at baseline and then at 6, 12, and 24 months after transplantation.

Patients are followed at 1 and 3 months, every 3 months through year 2, every 4 months through year 5, and then every 6 months thereafter.

PROJECTED ACCRUAL: A total of 80 patients (20 for regimen A and 60 for regimen B) will be accrued for this study.

Study Type : Interventional  (Clinical Trial)
Masking: None (Open Label)
Primary Purpose: Treatment
Study Start Date : September 1995
Actual Primary Completion Date : June 2003
Actual Study Completion Date : June 2003

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • One of the following diagnoses:

    • Histologically proven recurrent non-Hodgkin's lymphoma

      • Previously in complete remission (CR)
    • Refractory or recurrent intermediate-grade lymphoma (IGL) or high-grade immunoblastic lymphoma (IBL) meeting 1 of the following conditions:

      • In partial remission (PR) or CR to and currently enrolled on the MSKCC standard dose salvage regimen with ifosfamide, carboplatin, and etoposide (ICE)
      • In PR or CR after 1-2 other salvage chemotherapy regimens (e.g., 3 courses of dexamethasone, high-dose cytarabine, and cisplatin (DHAP); 2 courses of cyclophosphamide, mechlorethamine, vincristine, procarbazine, and prednisone (C-MOPP))

        • No prior ifosfamide
    • Low-grade lymphoma

      • In second or greater remission or chemosensitive relapse
      • No HLA identical sibling donor available
    • IGL or IBL

      • In first CR
      • Poor prognosis, defined by age-adjusted international index of 3 or 4 based on lactic dehydrogenase, number of extranodal sites, stage, and performance status
  • Adequate bone marrow cellularity
  • No lymphoblastic or small noncleaved cell lymphoma
  • Ineligible for total body irradiation (TBI) phase of study if prior radiotherapy dose precludes the use of TBI NOTE: A new classification scheme for adult non-Hodgkin's lymphoma has been adopted by PDQ. The terminology of "indolent" or "aggressive" lymphoma will replace the former terminology of "low", "intermediate", or "high" grade lymphoma.However, this protocol uses the former terminology.



  • Physiologic 18 to 65

Performance status:

  • Not specified


  • Not specified


  • Bilirubin no greater than 2.0 mg/dL (if no history of Gilbert's disease)
  • No chronic active or persistent hepatitis
  • Hepatitis B positivity allowed provided that the following conditions are met:

    • Bilirubin same as above*
    • SGPT no greater than 500 IU/L*
    • Alkaline phosphatase no greater than 2 times normal* NOTE: * In the absence of liver involvement by lymphoma


  • Creatinine no greater than 1.5 mg/dL OR
  • Creatinine clearance at least 60 mL/min
  • No history of chronic renal insufficiency


  • LVEF at least 50% by echocardiogram or MUGA scan
  • No myocardial infarction within the past 6 months
  • No unstable angina
  • No arrhythmia other than chronic atrial fibrillation


  • DLCO at least 50% predicted (corrected for hemoglobin and alveolar ventilation)


  • HIV negative
  • No uncontrolled infection
  • No other malignancy within the past 5 years except curatively treated basal cell skin cancer or carcinoma in situ of the cervix
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception


Biologic therapy

  • Not specified


  • See Disease Characteristics

Endocrine therapy

  • Not specified


  • See Disease Characteristics


  • Not specified

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00002697

United States, New York
Memorial Sloan-Kettering Cancer Center
New York, New York, United States, 10021
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
Study Chair: Craig Moskowitz, MD Memorial Sloan Kettering Cancer Center Identifier: NCT00002697     History of Changes
Other Study ID Numbers: 95-072
CDR0000064483 ( Registry Identifier: PDQ (Physician Data Query) )
First Posted: January 27, 2003    Key Record Dates
Last Update Posted: July 3, 2013
Last Verified: July 2013

Keywords provided by Memorial Sloan Kettering Cancer Center:
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent marginal zone lymphoma
recurrent small lymphocytic lymphoma
extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue
nodal marginal zone B-cell lymphoma
splenic marginal zone lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents