Clinical Trial: Comparison of Two Salvage Chemotherapy Regimens Before Autologous Stem Cell Transplantation With or Without Maintenance Rituximab in Treating Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

This study is currently recruiting patients.

Sponsored by: National Cancer Institute of Canada
Information provided by: National Cancer Institute (NCI)

Purpose

RATIONALE: Drugs used in chemotherapy, such as dexamethasone, cisplatin, gemcitabine, and cytarabine, work in different ways to stop cancer cells from dividing so they stop growing or die. Combining chemotherapy with autologous stem cell transplantation may allow the doctor to give higher doses of chemotherapy drugs and kill more cancer cells. Monoclonal antibodies, such as rituximab, can locate cancer cells and either kill them or deliver cancer-killing substances to them without harming normal cells. Giving rituximab as maintenance therapy after stem cell transplantation may kill any remaining cancer cells. It is not yet known which salvage chemotherapy regimen is more effective before autologous stem cell transplantation in treating relapsed or refractory non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying salvage chemotherapy using dexamethasone, cisplatin, and gemcitabine to see how well it works compared to dexamethasone, cisplatin, and cytarabine given before autologous stem cell transplantation in treating patients with relapsed or refractory aggressive non-Hodgkin's lymphoma. This trial also is studying giving rituximab as maintenance therapy to see how well it works compared to no further therapy after stem cell transplantation.

Condition Treatment or Intervention Phase
anaplastic large cell lymphoma
recurrent adult Burkitt's lymphoma
recurrent adult diffuse large cell lymphoma
angioimmunoblastic T-cell lymphoma
 Drug: cisplatin
 Drug: cytarabine
 Drug: dexamethasone
 Drug: gemcitabine
 Drug: rituximab
 Procedure: antibody therapy
 Procedure: autologous bone marrow transplantation
 Procedure: biological response modifier therapy
 Procedure: bone marrow ablation with stem cell support
 Procedure: bone marrow transplantation
 Procedure: chemotherapy
 Procedure: high-dose chemotherapy
 Procedure: monoclonal antibody therapy
 Procedure: peripheral blood stem cell transplantation
Phase III

MedlinePlus related topics:  Cancer;   Cancer Alternative Therapy;   Immune System and Disorders;   Lymphatic Diseases;   Lymphoma;   Viral Infections

Study Type: Interventional
Study Design: Treatment

Official Title: Phase III Randomized Study of Salvage Chemotherapy Comprising Dexamethasone, Cisplatin, and Gemcitabine Versus a Standard Platinum-Based Regimen (Dexamethasone, Cisplatin, and High-Dose Cytarabine) Before Autologous Stem Cell Transplantation and With or Without Maintenance Rituximab in Patients With Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Further Study Details: 

OBJECTIVES: Salvage therapy

Primary

Secondary

  • Compare the event-free and overall survival of patients treated with these regimens.
  • Compare the success rate of these regimens, in terms of getting patients to autologous stem cell transplantation and successful mobilization after high-dose chemotherapy.
  • Compare the quality of life of patients treated with these salvage regimens.
  • Compare the toxic effects of these salvage regimens in these patients.
  • Compare resource utilization for patients treated with these salvage regimens.
  • Compare relative medical and societal costs of these salvage regimens with outcomes in these patients.

Maintenance therapy

Primary

Secondary

OUTLINE: This is a randomized, multicenter study. For salvage therapy, patients are stratified according to participating center, International Prognostic Index score at relapse/study entry (0 or 1 vs 2 vs ≥ 3), immunophenotype (B cell vs T cell), response to or response duration after initial chemotherapy (no response or progressive disease vs > 1 year vs ≤ 1 year), and prior rituximab (yes vs no). For maintenance therapy, patients are stratified according to participating center, salvage therapy treatment randomization (cisplatin, dexamethasone, and gemcitabine vs cisplatin, dexamethasone, and cytarabine), response to salvage therapy (complete response [CR] and CR unconfirmed [CRu] vs partial response [PR] vs stable disease [SD]), and prior rituximab (yes vs no).

  • Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Patients receive cisplatin IV over 60 minutes on day 1, dexamethasone IV or orally on days 1-4, and gemcitabine IV over 30 minutes on days 1 and 8.
  • Arm II: Patients receive cisplatin IV over 24 hours on day 1, dexamethasone as in arm I, and cytarabine IV over 3 hours every 12 hours for a total of 2 doses on day 2. In both arms, treatment repeats every 21 days for at least 2 courses in the absence of disease progression or unacceptable toxicity.

Patients are reassessed after 2 courses. Patients with progressive disease are removed from study. Patients with a CR, CRu, or PR proceed to autologous stem cell transplantation (ASCT). Patients with SD may proceed to ASCT or receive 1 additional course of salvage therapy at the discretion of the investigator. Patients receiving an additional course of salvage therapy are then reassessed after the completion of therapy. Patients with progressive disease are removed from study. Patients with a PR proceed to ASCT. Patients with SD may proceed to ASCT or be followed off study at the discretion of the investigator.

  • ASCT: Responding patients (or those with stable disease, if that is the center's policy)undergo mobilization, stem cell harvest, and subsequent ASCT. Patients with CD20+ B-cell disease are randomized to maintenance therapy or observation.
  • Patients are randomized to 1 of 2 treatment arms.
  • Arm I: Beginning on day 28 posttransplantation, patients receive rituximab IV once every 2 months for 6 doses (a total of 12 months) in the absence of disease progression or unacceptable toxicity.
  • Arm II: Patients undergo observation only. Quality of life is assessed at baseline, days 1 and 10 of course 2, day 1 of course 3 (if given), on the last day of salvage therapy (or the first day of mobilization, if given), and at 1 month posttransplantation.

Patients who undergo ASCT are followed at months 1, 3, 7, 13, 19, and 25 and then annually thereafter. Patients who complete salvage therapy, but do not undergo ASCT are followed at months 4, 8, 14, 20, and 26 and then annually thereafter. Patients who relapse or progress are followed every 6 months until 25 months from ASCT or 26 months from completion of salvage therapy and then annually thereafter.

PROJECTED ACCRUAL: A total of 630 patients will be accrued for this study within 3-4 years for the first randomization, and 240 transplanted CD20+ patients will be needed for the second randomization.

Eligibility

Ages Eligible for Study:  16 Years   -   65 Years,  Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed aggressive non-Hodgkin's lymphoma of 1 of the following subtypes:
  • Diffuse large cell lymphoma (includes primary mediastinal B-cell lymphoma and T-cell-rich B-cell lymphoma)
  • Prior indolent lymphoma (e.g., follicular center cell lymphoma; marginal zone lymphoma, including extranodal mucosa-associated lymphoid tissue [MALT] lymphoma; and lymphoplasmacytoid lymphoma) with transformation to diffuse large B-cell lymphoma at relapse
  • Must be histologically confirmed
  • No transformed lymphoma at diagnosis with subsequent indolent histology without transformation at relapse
  • Peripheral T-cell lymphoma
  • Anaplastic large cell lymphoma
  • Small noncleaved Burkitt-like lymphoma
  • T-cell or B-cell lineage confirmed by immunohistochemistry
  • Clinically or radiologically documented disease meeting either of the following criteria:
  • Measurable disease, defined as at least 1 bidimensionally measurable site of disease using clinical exam, CT scan, or MRI
  • Lymph nodes must be > 1.5 cm by physical exam or CT scan
  • Other non-nodal lesions must be ≥ 1.0 cm by physical exam, CT scan, or MRI
  • Bone lesions are not considered measurable
  • Evaluable disease, defined as only nonmeasurable disease, including any of the following:
  • Marrow infiltration
  • Cytology-confirmed ascites or effusions
  • Bony involvement
  • Enlarged liver or spleen
  • Unidimensionally measurable intrathoracic or abdominal masses
  • Previously treated with 1, and only 1, chemotherapy regimen including an anthracycline and excluding cisplatin, cytarabine, and gemcitabine
  • No uncontrolled CNS involvement by lymphoma
  • No CNS disease at time of relapse
  • CNS disease diagnosed at initial presentation allowed provided a complete response for CNS disease was achieved and maintained

PATIENT CHARACTERISTICS: Age

  • 16 to 65

Performance status

  • ECOG 0-3

Life expectancy

  • At least 12 weeks

Hematopoietic

  • Absolute granulocyte count ≥ 1,000/mm^3
  • Platelet count ≥ 75,000/mm^3

Hepatic

  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST or ALT ≤ 2.5 times ULN (5 times ULN if liver involvement with lymphoma)
  • Hepatitis B status known (for patients with a history of hepatitis B or who are at high risk of hepatitis B infection)

Renal

  • Creatinine ≤ 1.5 times ULN

Cardiovascular

Other

  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • Willing to complete quality of life questionnaires
  • HIV negative
  • No active, uncontrolled bacterial, fungal, or viral infection
  • No other malignancy within the past 5 years except adequately treated basal cell skin cancer or carcinoma in situ of the cervix
  • No other concurrent serious illness or medical condition that would preclude study participation

PRIOR CONCURRENT THERAPY: Biologic therapy

Chemotherapy

Endocrine therapy

  • No concurrent corticosteroids except for physiologic replacement

Radiotherapy

  • At least 4 weeks since prior radiotherapy and recovered
  • Exceptions may be made for low-dose, non-myelosuppressive radiotherapy
  • No prior radiotherapy to more than 25% of functioning bone marrow
  • Involved-field radiotherapy may be given to areas of bulky disease at relapse (≥ 5 cm) after stem cell transplantation, according to the center's policy

Surgery

  • At least 2 weeks since prior major surgery

Other

  • No other concurrent anticancer therapy
  • No other concurrent experimental agents

Location and Contact Information


New Jersey
      Cancer Center at Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States; Recruiting
Jack Hsu, MD  201-996-5900 

North Carolina
      Duke Comprehensive Cancer Center, Durham,  North Carolina,  27710,  United States; Recruiting
David A. Rizzieri, MD  919-668-1040 

Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada; Recruiting
A. Robert Turner, MD  780-432-8514    roberttu@cancerboard.ab.ca 

      Tom Baker Cancer Centre - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada; Recruiting
Douglas A. Stewart, MD  403-944-1707 

Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada; Recruiting
Morel Rubinger, MD, FRCPC  204-787-2113    Morel.rubinger@cancercare.mb.ca 

Canada, New Brunswick
      Doctor Leon Richard Oncology Centre, Moncton,  New Brunswick,  E1C 8X3,  Canada; Recruiting
Jean-Marie Vantelon, MD  506-862-4030 

      Moncton Hospital, Moncton,  New Brunswick,  E1C 6ZB,  Canada; Recruiting
Sheldon H. Rubin, MD  506-857-2881    shrubin@sehcc.health.nb.ca 

Canada, Newfoundland and Labrador
      Newfoundland Cancer Treatment and Research Foundation, St. Johns,  Newfoundland and Labrador,  A1B 3V6,  Canada; Recruiting
Kuljit Grewal  709-777-7061    kgrewal@mvn.ca 

Canada, Nova Scotia
      Nova Scotia Cancer Centre at Queen Elizabeth II Health Sciences Centre, Halifax,  Nova Scotia,  B3H 2Y9,  Canada; Recruiting
Stephen Couban, MD  902-473-7005    stephen.couban@cdha.nsheall.ca 

Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting
Kang Howson-Jan, MD  519-685-5194 

      Cancer Centre of Southeastern Ontario, Kingston,  Ontario,  K7L 5P9,  Canada; Recruiting
Tara Baetz, MD  613-544-2630    tara.baetz@krcc.on.ca 

      Carlo Fidani Peel Regional Cancer Centre at Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada; Recruiting
Peter James Anglin, MD  905-813-2200 

      Hotel Dieu Health Sciences Hospital - Niagara, St. Catharines,  Ontario,  L2R 5K3,  Canada; Recruiting
Brian Peter Findlay, MD  905-682-6451 

      Margaret and Charles Juravinski Cancer Centre, Hamilton,  Ontario,  L8V 5C2,  Canada; Recruiting
Ralph M. Meyer, MD, FRCPC  905-575-7820    ralph.meyer@hrcc.on.ca 

      McMaster Children's Hospital at Hamilton Health Sciences, Hamilton,  Ontario,  ON L8N 3Z5,  Canada; Recruiting
Parveen Wasi, MD  905-521-2100, ext. 73390 

      Princess Margaret Hospital, Toronto,  Ontario,  M5G 2M9,  Canada; Recruiting
Michael R. Crump, MD, FRCPC  416-946-4567    michael.crump@uhn.on.ca 

      Regional Cancer Care at Thunder Bay Regional Health Sciences Centre, Thunder Bay,  Ontario,  P7B 6V4,  Canada; Recruiting
Dimitrios Vergidis, MD  807-684-7200    vergidid@tbh.net 

      Toronto Sunnybrook Regional Cancer Centre, Toronto,  Ontario,  M4N 3M5,  Canada; Recruiting
Kevin Imrie, MD  416-480-4757    kevin.imrie@utoronto.ca 

Canada, Quebec
      Centre Hospitalier Universitaire de Quebec, Quebec City,  Quebec,  G1R 2J6,  Canada; Recruiting
Alain Filion, MD, FRCPC  418-835-7121    alfilion@videotron.ca 

      CHUS-Hopital Fleurimont, Sherbrooke,  Quebec,  J1H 5N4,  Canada; Recruiting
Richard Leblanc, MD  819-346-1110 ext. 14816 

      Hopital Charles Lemoyne, Greenfield Park,  Quebec,  J4V 2H1,  Canada; Recruiting
Pierre Desjardins, MD  450-466-5065 

      Hopital Du Sacre-Coeur de Montreal, Montreal,  Quebec,  H4J 1C5,  Canada; Recruiting
Guylaine Gaudet, MD  514-338-2050    guylainegaudet@hotmail.com 

      Hopital du Saint-Sacrement, Quebec, Quebec City,  Quebec,  G1S 4L8,  Canada; Recruiting
Guy Cantin, MD  418-682-7511 

      Hopital Notre- Dame du CHUM, Montreal,  Quebec,  H2L 4M1,  Canada; Recruiting
Harold J. Olney, MD  514-890-8200 

      Hotel-Dieu de Levis, Levis,  Quebec,  G6V 3Z1,  Canada; Recruiting
Alain Filion, MD, FRCPC  418-835-7121    alfilion@videotron.ca 

      Maisonneuve-Rosemont Hospital, Montreal,  Quebec,  H1T 2M4,  Canada; Recruiting
Julie Beaudet, MD  514-252-3404 

Canada, Saskatchewan
      Allan Blair Cancer Centre at Pasqua Hospital, Regina,  Saskatchewan,  S4T 7T1,  Canada; Recruiting
Haji Ibrahim Chalchal, MD  306-766-2691    hchalchal@scf.sk.ca 

      Saskatoon Cancer Centre, Saskatoon,  Saskatchewan,  S7N 4H4,  Canada; Recruiting
Michael Voralia  306-655-2925 

Study chairs or principal investigators

Massimo Federico, MD,  Study Chair,  University of Modena and Reggio Emilia School of Medicine   

More Information

Clinical trial summary from the National Cancer Institute's PDQ® database

Study ID Numbers:  CDR0000353203; CAN-NCIC-LY.12; NCT00078949
Record last reviewed:  March 2005
Last Updated:  April 5, 2005
Record first received:  March 8, 2004
ClinicalTrials.gov Identifier:  NCT00078949
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005