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
15 Years
65 Years
Both
Lymphoma
Trial Information
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
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Survival
Outcome Time Frame:
until death
Safety Issue:
No
Principal Investigator
Patrick J. Stiff, MD
Investigator Role:
Study Chair
Investigator Affiliation:
Loyola University
Authority:
United States: Food and Drug Administration
Study ID:
CDR0000065658
NCT ID:
NCT00004031
Start Date:
July 1997
Completion Date:
Related Keywords:
- Lymphoma
- 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
- Lymphoma, Large-Cell, Immunoblastic
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