SWOG-9704 Chemoradiotherapy and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma

This study has been completed.
Sponsor:
Collaborators:
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Information provided by (Responsible Party):
Southwest Oncology Group
ClinicalTrials.gov Identifier:
NCT00004031
First received: December 10, 1999
Last updated: May 22, 2013
Last verified: May 2013
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop cancer cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage cancer cells. Peripheral stem cell transplantation may allow the doctor to give higher doses of chemotherapy and radiation and kill more cancer cells. It is not yet known whether chemoradiotherapy plus peripheral stem cell transplantation is more effective than combination chemotherapy alone in treating non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying chemoradiotherapy and peripheral stem cell transplantation to see how well they work compared to combination chemotherapy in treating patients with stage II, stage III, or stage IV non-Hodgkin's lymphoma.


Condition Intervention Phase
Lymphoma
Biological: rituximab
Drug: CHOP regimen
Drug: carmustine
Drug: cyclophosphamide
Drug: doxorubicin hydrochloride
Drug: etoposide
Drug: prednisone
Drug: vincristine sulfate
Procedure: bone marrow ablation with stem cell support
Procedure: peripheral blood stem cell transplantation
Radiation: radiation therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: SWOG-9704 A Randomized Phase III Trial Comparing Early High Dose Chemoradiotherapy and an Autologous Stem Cell Transplant to Conventional Dose CHOP Chemotherapy Plus Rituximab for CD20+ B Cell Lymphomas (With Possible Late Autologous Stem Cell Transplant) for Patients With Diffuse Aggressive Non-Hodgkin's Lymphoma in the High-Intermediate and High Risk International Classification Prognostic Groups

Resource links provided by NLM:


Further study details as provided by Southwest Oncology Group:

Primary Outcome Measures:
  • Survival [ Time Frame: until death ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: until death ] [ Designated as safety issue: No ]

Enrollment: 397
Study Start Date: July 1997
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: CHOP/CHOP-R x 3
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Prednisone 100 mg/day PO Days 1-5 Vincristine 1.4 mg/m2 IV Day 1 Rituximab 375 mg/m2 IV Day 1 This regimen is repeated every 21 days for 8 cycles
Biological: rituximab
375 mg/m2 IV every 21 days
Drug: CHOP regimen Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: prednisone Drug: vincristine sulfate Procedure: bone marrow ablation with stem cell support
Experimental: CHOP/CHOP-R x 1 + Autologous Stem Cell Transplant
Cyclophosphamide 750 mg/m2 IV Day 1 Doxorubicin 50 mg/m2 IV Day 1 Prednisone 100 mg/day PO Days 1-5 Vincristine 1.4 mg/m2 IV Day 1 Rituximab 375 mg/m2 IV Day 1 This regimen is repeated every 21 days for 6 cycles followed by autologous stem cell transplant.
Biological: rituximab
375 mg/m2 IV every 21 days
Drug: CHOP regimen Drug: carmustine Drug: cyclophosphamide Drug: doxorubicin hydrochloride Drug: etoposide Drug: prednisone Drug: vincristine sulfate Procedure: bone marrow ablation with stem cell support Procedure: peripheral blood stem cell transplantation Radiation: radiation therapy

Detailed Description:

OBJECTIVES:

  • Compare the overall survival and progression-free survival of patients with intermediate- or high-grade non-Hodgkin's lymphoma treated with high-dose chemoradiotherapy and autologous peripheral blood stem cell transplantation (APBSCT) vs conventional dose cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (or CHOP plus rituximab for CD20+ disease) with possible late APBSCT.
  • Compare the toxic effects of these regimens in this patient population.

OUTLINE: This is a randomized study. Patients are stratified according to disease risk (intermediate-high vs high).

Patients receive CHOP chemotherapy comprising cyclophosphamide IV over 15 minutes, doxorubicin IV, and vincristine IV on day 1 and oral prednisone on days 1-5. Patients with CD20-positive disease also receive rituximab IV on day 1 (or day 0 during course 1 only). Treatment repeats every 3 weeks for 5 courses in the absence of disease progression or unacceptable toxicity.

Within 35 days of completing the fifth course, patients with partial or complete response are randomized to one of two treatment arms.

  • Arm I: Patients receive CHOP (or CHOP plus rituximab [CHOP-R]) as above. Treatment repeats every 3 weeks for 3 additional courses. After completion of chemotherapy, patients are encouraged to undergo harvest of peripheral blood stem cells (PBSC) for possible use at time of relapse. After completion of 8 courses, patients receive no additional therapy until disease progression or biopsy-proven disease.
  • Arm II: Patients receive one additional course of CHOP/CHOP-R followed by filgrastim (G-CSF), sargramostim (GM-CSF), or other colony-stimulating factors used singly or in combination according to center preference. PBSC are harvested and selected for CD34+ cells. Patients under age 61 receive one of two preparative regimens: a total body irradiation (TBI)-based regimen comprising irradiation administered twice daily on days -8 to -5, etoposide IV over 4 hours on day -4, and cyclophosphamide IV over 1 hour on day -2 OR carmustine IV over 2 hours on days -6 to -4 and etoposide and cyclophosphamide as in the TBI-based regimen. Patients age 61 to 65 receive the augmented regimen comprising carmustine, etoposide, and cyclophosphamide as above. Patients receive involved field radiotherapy prior to the preparative regimen only if there is biopsy-proven residual bulk disease and at the discretion of the center. PBSC are reinfused 36-48 hours after completion of cyclophosphamide. If both bone marrow and PBSC are harvested, bone marrow is reinfused on day 0 and then PBSC are reinfused either the same day or the following day.

Patients are followed every 6 months for 2 years and then annually thereafter.

PROJECTED ACCRUAL: Approximately 360 patients (at least 135 per treatment arm) will be accrued for this study within 5 years.

  Eligibility

Ages Eligible for Study:   15 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically proven intermediate- or high-grade non-Hodgkin's lymphoma
  • Ann Arbor classification of "bulky" stage II, III, or IV
  • Must be classified as high-intermediate or high-risk according to International Age Adjusted Index
  • Bidimensionally measurable disease
  • No lymphoblastic, transformed, or mantle cell lymphomas
  • No CNS involvement by lymphoma
  • CD20 status confirmed by immunocytochemistry or flow cytometry
  • Must have either bilateral or unilateral bone marrow aspiration and biopsy ≥ 42 days before first course of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) therapy (or CHOP plus rituximab [CHOP-R] for CD20+ disease) OR within 42 days prior to registration if CHOP/CHOP-R therapy has not begun
  • Must have bilateral bone marrow aspiration and biopsy within 28 days of randomization

    • Bone marrow involvement with lymphoma is allowed, provided there is an improvement of at least 50% if used as an evaluable site of disease
  • No prior lymphoma, Hodgkin's lymphoma, myelodysplastic syndromes, or leukemia 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.

PATIENT CHARACTERISTICS:

Age:

  • 15 to 65

Performance status:

  • Not specified

Life expectancy:

  • Not specified

Hematopoietic:

  • Not specified

Hepatic:

  • Bilirubin no greater than 1.5 times upper limit of normal (ULN)
  • No nonlymphoma-related hepatic dysfunction

Renal:

  • Creatinine no greater than 2 times ULN
  • Creatinine clearance at least 60 mL/min
  • No nonlymphoma-related renal dysfunction
  • No history of grade 3 hemorrhagic cystitis due to cyclophosphamide

Cardiovascular:

  • No coronary artery disease, cardiomyopathy, congestive heart failure, or dysrhythmia requiring therapy
  • MUGA scan or 2-D echocardiogram required if patient's history is questionable
  • Ejection fraction normal

Pulmonary:

  • DLCO or FEV_1 at least 60% of predicted

Other:

  • Not pregnant or nursing
  • Fertile patients must use effective contraception
  • HIV negative
  • No other malignancy within the past 5 years except basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
  • No allergy to etoposide
  • No active bacterial, fungal, or viral infection

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • No prior monoclonal antibody therapy for lymphoma except if included in a single course of CHOP/CHOP-R

Chemotherapy:

  • No prior chemotherapy for lymphoma except for a single course of CHOP/CHOP-R* NOTE: *Prednisone or other corticosteroids not considered prior chemotherapy

Endocrine therapy:

  • See Chemotherapy
  • Prior corticosteroids allowed

Radiotherapy:

  • No prior radiotherapy for lymphoma
  • No prior thoracic radiotherapy or radiotherapy greater than 2,000 cGy to any other site

Surgery:

  • Not specified
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00004031

Locations
Canada, Alberta
Tom Baker Cancer Centre - Calgary
Calgary, Alberta, Canada, T2N 4N2
Cross Cancer Institute at University of Alberta
Edmonton, Alberta, Canada, T6G 1Z2
Canada, Manitoba
CancerCare Manitoba
Winnipeg, Manitoba, Canada, R3E 0V9
Canada, New Brunswick
Moncton Hospital
Moncton, New Brunswick, Canada, E1C 6Z8
Canada, Newfoundland and Labrador
Doctor H. Bliss Murphy Cancer Centre
St. John's, Newfoundland and Labrador, Canada, AIB 3V6
Canada, Nova Scotia
Nova Scotia Cancer Centre
Halifax, Nova Scotia, Canada, B3H 1V7
Canada, Ontario
Margaret and Charles Juravinski Cancer Centre
Hamilton, Ontario, Canada, L8V 5C2
London Regional Cancer Program at London Health Sciences Centre
London, Ontario, Canada, N6A 4L6
Odette Cancer Centre at Sunnybrook
Toronto, Ontario, Canada, M4N 3M5
Canada, Quebec
Hopital Du Sacre-Coeur de Montreal
Montreal, Quebec, Canada, H4J 1C5
Hopital Notre-Dame du CHUM
Montreal, Quebec, Canada, H2L 4M1
Hopital du Saint-Sacrement - Quebec
Quebec City, Quebec, Canada, G1S 4L8
Centre Hospitalier Universitaire de Quebec
Quebec City, Quebec, Canada, G1R 2J6
Canada, Saskatchewan
Saskatoon Cancer Centre at the University of Saskatchewan
Saskatoon, Saskatchewan, Canada, S7N 4H4
Sponsors and Collaborators
Southwest Oncology Group
Cancer and Leukemia Group B
Eastern Cooperative Oncology Group
NCIC Clinical Trials Group
Investigators
Study Chair: Patrick J. Stiff, MD Loyola University
Study Chair: Thomas C. Shea, MD UNC Lineberger Comprehensive Cancer Center
Study Chair: David P. Schenkein, MD Tufts Medical Center Cancer Center
Study Chair: Stephen Couban, MD Cancer Care Nova Scotia
  More Information

Additional Information:
Publications:
Stiff PJ, Unger JM, Cook J, et al.: Randomized phase III U.S./Canadian intergroup trial (SWOG S9704) comparing CHOP ± R for eight cycles to CHOP ± R for six cycles followed by autotransplant for patients with high-intermediate (H-Int) or high IPI grade diffuse aggressive non-Hodgkin lymphoma (NHL). [Abstract] J Clin Oncol 29 (Suppl 15): A-8001, 2011.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Southwest Oncology Group
ClinicalTrials.gov Identifier: NCT00004031     History of Changes
Other Study ID Numbers: CDR0000065658, S9704, U10CA032102
Study First Received: December 10, 1999
Last Updated: May 22, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Southwest Oncology Group:
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult Burkitt lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult Burkitt lymphoma
contiguous stage II grade 3 follicular lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
contiguous stage II adult diffuse mixed cell lymphoma
contiguous stage II adult immunoblastic large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
contiguous stage II adult Burkitt lymphoma
noncontiguous stage II grade 3 follicular lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II adult diffuse mixed cell lymphoma
noncontiguous stage II adult immunoblastic large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult Burkitt lymphoma

Additional relevant MeSH terms:
Lymphoma
Lymphoma, Non-Hodgkin
Lymphoma, Large-Cell, Immunoblastic
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Carmustine
Cyclophosphamide
Rituximab
Doxorubicin
Etoposide
Prednisone
Vincristine
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Antineoplastic Agents, Phytogenic
Glucocorticoids

ClinicalTrials.gov processed this record on April 17, 2014