SWOG-9704 Chemoradiotherapy and Peripheral Stem Cell Transplantation Compared With Combination Chemotherapy in Treating Patients With Non-Hodgkin's Lymphoma
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ClinicalTrials.gov Identifier: NCT00004031 |
Recruitment Status :
Completed
First Posted : January 27, 2003
Results First Posted : February 2, 2021
Last Update Posted : February 2, 2021
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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 or disease | Intervention/treatment | Phase |
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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 |
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.
Study Type : | Interventional (Clinical Trial) |
Actual Enrollment : | 397 participants |
Allocation: | Randomized |
Intervention Model: | Single Group Assignment |
Masking: | None (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 |
Study Start Date : | July 1997 |
Actual Primary Completion Date : | June 1, 2008 |
Actual Study Completion Date : | October 31, 2013 |
Arm | Intervention/treatment |
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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
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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.
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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 |
- 2-year Overall Survival Rates [ Time Frame: up to 2 years post registration ]Percentage of participants surviving 2 years post registration
- 2 Year Progression-free Survival [ Time Frame: From registration until death ]Percentage of participants without disease progression up to 2 years post-registration.
- Number of Patients With Gr 3 Through 5 Adverse Events That Are Related to Study Drugs [ Time Frame: Duration of treatment and follow up until death or 3 years post registration ]
Adverse Events (AEs) are reported by CTCAE Version 2.0. Only adverse events that are possibly, probably or definitely related to study drug are reported.
Higher grades indicate higher severity of adverse events.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 15 Years to 65 Years (Child, Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
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
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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
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 ClinicalTrials.gov identifier (NCT number): NCT00004031
United States, Oregon | |
Oregon Health & Science University | |
Portland, Oregon, United States, 97201 | |
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 Notre-Dame du CHUM | |
Montreal, Quebec, Canada, H2L 4M1 | |
Hopital Du Sacre-Coeur de Montreal | |
Montreal, Quebec, Canada, H4J 1C5 | |
Centre Hospitalier Universitaire de Quebec | |
Quebec City, Quebec, Canada, G1R 2J6 | |
Hopital du Saint-Sacrement - Quebec | |
Quebec City, Quebec, Canada, G1S 4L8 | |
Canada, Saskatchewan | |
Saskatoon Cancer Centre at the University of Saskatchewan | |
Saskatoon, Saskatchewan, Canada, S7N 4H4 |
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 |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: | SWOG Cancer Research Network |
ClinicalTrials.gov Identifier: | NCT00004031 |
Other Study ID Numbers: |
CDR0000065658 S9704 ( Other Identifier: SWOG ) U10CA032102 ( U.S. NIH Grant/Contract ) |
First Posted: | January 27, 2003 Key Record Dates |
Results First Posted: | February 2, 2021 |
Last Update Posted: | February 2, 2021 |
Last Verified: | January 2021 |
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 |
Lymphoma Lymphoma, Non-Hodgkin Neoplasms by Histologic Type Neoplasms Lymphoproliferative Disorders Lymphatic Diseases Immunoproliferative Disorders Immune System Diseases Prednisone Cyclophosphamide Carmustine Rituximab Doxorubicin Liposomal doxorubicin Etoposide |
Vincristine Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs Antirheumatic Agents Antineoplastic Agents, Alkylating Alkylating Agents Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Myeloablative Agonists Antineoplastic Agents, Immunological Antibiotics, Antineoplastic Topoisomerase II Inhibitors Topoisomerase Inhibitors Enzyme Inhibitors |