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Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas


Phase 3
18 Years
N/A
Open (Enrolling)
Both
Lymphoma

Thank you

Trial Information

Phase III Randomized Study of R-CHOP V. Dose-Adjusted EPOCH-R With Molecular Profiling in Untreated De Novo Diffuse Large B-Cell Lymphomas


OBJECTIVES:

Primary

- Compare the event-free survival of patients with previously untreated de novo diffuse
large B-cell non-Hodgkin's lymphoma treated with R-CHOP comprising rituximab,
cyclophosphamide, doxorubicin, vincristine, and prednisone vs EPOCH-R comprising
etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab.

- Determine molecular predictors of outcome (using molecular profiling) in patients
treated with these regimens.

Secondary

- Compare the response rate and overall survival of patients treated with these regimens.

- Compare the toxicity of these regimens in these patients.

- Correlate the clinical parameters (i.e., toxicity, response, survival outcomes, and
laboratory results) with molecular profiling in patients treated with these regimens.

- Assess the use of molecular profiling for pathological diagnosis in patients treated
with these regimens.

- Identify new therapeutic targets using molecular profiling.

- Perform a comprehensive analysis of somatic alterations to the tumor genome in order to
understand which genomic alterations are somatically acquired by the tumor and which
are encoded in the germ line of the patient.

- Identify biomarkers of response to chemotherapy by FDG-PET/CT imaging that are
predictive of histopathologic remissions and survival in patients with stage I
(mediastinal), II, III, or IV untreated DLBCL.

- Evaluate the use of semiquantitative measurements of FDG uptake in defining
FDG-PET/CT-based biomarkers of response to chemotherapy in patients with DLBCL.

- Determine whether FDG-PET/CT measurements of tumor response after the second cycle of
chemotherapy can predict clinical response.

- Establish a standardized protocol for FDG-PET/CT image acquisition.

- Determine additional FDG-PET/CT parameters (e.g., the ratio of tumor SUVmax to liver
SUVmean; SUVs corrected for body surface area and lean body mass; nuclear medicine
physician's assessment) and evaluate their utility in refining FDG-PET/CT based
biomarkers of response to therapy.

- Evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this
indication.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to
International Prognostic Index score. Patients are randomized to 1 of 2 treatment arms.

- Arm I (R-CHOP): Patients receive rituximab IV, cyclophosphamide IV, doxorubicin IV over
3-5 minutes, and vincristine IV on day 1 and oral prednisone once daily on days 1-5.
Treatment repeats every 21 days for 6 courses in the absence of disease progression or
unacceptable toxicity.

- Arm II (EPOCH-R): Patients receive rituximab IV on day 1, doxorubicin IV, etoposide IV,
and vincristine IV continuously over 96 hours on days 1-4, cyclophosphamide IV on day
5, and oral prednisone twice daily on days 1-5. Patients also receive filgrastim
(G-CSF) once daily on days 2-11 or until blood counts recover. Treatment repeats every
21 days for 6 courses in the absence of disease progression or unacceptable toxicity.

As of July 1, 2012, the FDG-PET/CT imaging companion study CALGB-580603 will be required of
all patients enrolling on this study. FDG-PET/CT scans of abdomen/chest/pelvis are collected
at baseline, post-course 2, and post-course 6.

After completion of study treatment, patients are followed every 3 months for 2 years and
then every 6 months for up to 3 years.

PROJECTED ACCRUAL: A total of 478 patients (239 per treatment arm) will be accrued for this
study within 4.5 years.

Inclusion Criteria


DISEASE CHARACTERISTICS:

- Histologically confirmed* de novo B-cell non-Hodgkin's lymphoma (NHL) of 1 of the
following WHO histologic subtypes:

- Diffuse large cell lymphoma, including any of the following morphologic
variants:

- Centroblastic

- Immunoblastic

- T-cell/histiocyte rich

- Anaplastic

- Mediastinal (thymic) large cell lymphoma

- Intravascular large cell lymphoma NOTE: *Fine needle aspirates or core biopsies
must not be the only diagnostic material

- Stage I primary mediastinal (thymic) OR stage II-IV disease

- CD20-positive disease

- No underlying low-grade lymphoma (e.g., transformed lymphoma or low-grade lymphoma in
the bone marrow)

- No known lymphomatous CNS involvement

- Lumbar puncture required unless there are no neurological symptoms

- As of July 1, 2012, the PET/CT imaging companion study CALGB-580603 will be required
of all patients enrolling onto the treatment study CALGB-50303 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

- 18 and over

Performance status

- ECOG 0-2

Life expectancy

- Not specified

Hematopoietic

- Absolute neutrophil count ≥ 1,000/mm^3^*

- Platelet count ≥ 100,000/mm^3^*

- No active bleeding unrelated to NHL NOTE: *Unless due to NHL

Hepatic

- Bilirubin ≤ 2 mg/dL* NOTE: *Unless due to NHL or Gilbert's disease

Renal

- Creatinine ≤ 1.5 mg/dL^* OR

- Creatinine clearance ≥ 50 mL/min^* NOTE: *Unless due to NHL

Cardiovascular

- No active ischemic heart disease

- No congestive heart failure

Other

- Not pregnant or nursing

- Negative pregnancy test

- Fertile patients must use effective contraception

- HIV negative

- No active uncontrolled bacterial or viral infection unrelated to NHL

- No other active medical process unrelated to NHL

PRIOR CONCURRENT THERAPY:

Biologic therapy

- No prior rituximab

Chemotherapy

- No prior chemotherapy for other malignancies

- No prior cytotoxic chemotherapy

- No other concurrent chemotherapy

Endocrine therapy

- Prior short course (< 10 days) glucocorticoids allowed for an urgent local disease
complication (e.g., cord compression or superior vena cava syndrome) at diagnosis

- No concurrent hormonal therapy except steroids for adrenal failure or hormones for
non-disease related conditions (e.g., insulin for diabetes)

- No concurrent dexamethasone or other steroidal antiemetics

Radiotherapy

- Prior limited field radiotherapy allowed for an urgent local disease complication
(e.g., cord compression or superior vena cava syndrome) at diagnosis

- No concurrent radiotherapy except for isolated CNS lesions

Surgery

- Not specified

Other

- No other concurrent investigational or commercial agents or therapies for NHL

Type of Study:

Interventional

Study Design:

Allocation: Randomized, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Event-free survival 5 years after completion of study treatment

Safety Issue:

No

Principal Investigator

Wyndham H. Wilson, MD, PhD

Investigator Role:

Study Chair

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

Unspecified

Study ID:

CDR0000433265

NCT ID:

NCT00118209

Start Date:

May 2005

Completion Date:

Related Keywords:

  • Lymphoma
  • stage I adult diffuse large cell lymphoma
  • contiguous stage II adult diffuse large cell lymphoma
  • noncontiguous stage II adult diffuse large cell lymphoma
  • stage III adult diffuse large cell lymphoma
  • stage IV adult diffuse large cell lymphoma
  • Lymphoma
  • Lymphoma, Non-Hodgkin
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse

Name

Location

National Naval Medical CenterBethesda, Maryland  20889
Cardinal Bernardin Cancer Center at Loyola University Medical CenterMaywood, Illinois  60153-5500
CCOP - Christiana Care Health ServicesWilmington, Delaware  19899
Mercy Cancer Center at Mercy Medical CenterCanton, Ohio  44708
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical CenterWilkes-Barre, Pennsylvania  18711
Marshfield Clinic - Marshfield CenterMarshfield, Wisconsin  54449
Marshfield Clinic - Indianhead CenterRice Lake, Wisconsin  54868
Naval Medical Center - San DiegoSan Diego, California  92134-3202
Rebecca and John Moores UCSD Cancer CenterLa Jolla, California  92093-0658
Alvin and Lois Lapidus Cancer Institute at Sinai HospitalBaltimore, Maryland  21215
Presbyterian Cancer Center at Presbyterian HospitalCharlotte, North Carolina  28233-3549
Wake Forest University Comprehensive Cancer CenterWinston-Salem, North Carolina  27157-1096
Mary Babb Randolph Cancer Center at West Virginia University HospitalsMorgantown, West Virginia  26506
James P. Wilmot Cancer Center at University of Rochester Medical CenterRochester, New York  14642
New York Weill Cornell Cancer Center at Cornell UniversityNew York, New York  10021
University of Illinois Cancer CenterChicago, Illinois  60612-7243
Siteman Cancer Center at Barnes-Jewish Hospital - Saint LouisSt. Louis, Missouri  63110
Geisinger Cancer Institute at Geisinger HealthDanville, Pennsylvania  17822-0001
Virginia Commonwealth University Massey Cancer CenterRichmond, Virginia  23298-0037
Madigan Army Medical Center - TacomaTacoma, Washington  98431
Robert H. Lurie Comprehensive Cancer Center at Northwestern UniversityChicago, Illinois  60611
Providence Cancer Institute at Providence Hospital - Southfield CampusSouthfield, Michigan  48075
Charles R. Wood Cancer Center at Glens Falls HospitalGlens Falls, New York  12801
Iredell Memorial HospitalStatesville, North Carolina  28677
Mountainview MedicalBerlin, Vermont  05602
NIH - Warren Grant Magnuson Clinical CenterBethesda, Maryland  20892-1182
Palo Alto Medical FoundationPalo Alto, California  94301
Creticos Cancer Center at Advocate Illinois Masonic Medical CenterChicago, Illinois  60657
Altru Cancer Center at Altru HospitalGrand Forks, North Dakota  58201
Western Pennsylvania Cancer Institute at Western Pennsylvania HospitalPittsburgh, Pennsylvania  15224-1791
Eastern Connecticut Hematology and Oncology AssociatesNorwich, Connecticut  06360
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer CenterColumbus, Ohio  43210-1240
Geisinger Hazleton Cancer CenterHazleton, Pennsylvania  18201
Penn State Hershey Cancer Institute at Milton S. Hershey Medical CenterHershey, Pennsylvania  17033-0850
Saint Joseph's HospitalMarshfield, Wisconsin  54449
Marshfield Clinic - Lakeland CenterMinocqua, Wisconsin  54548
Ministry Medical Group at Saint Mary's HospitalRhinelander, Wisconsin  54501
Marshfield Clinic at Saint Michael's HospitalStevens Point, Wisconsin  54481
Saint Michael's Hospital Cancer CenterStevens Point, Wisconsin  54481
Marshfield Clinic - Weston CenterWeston, Wisconsin  54476
Easton Regional Cancer Center at Easton HospitalEaston, Pennsylvania  18042
Kinston Medical SpecialistsKinston, North Carolina  28501
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer CareConcord, New Hampshire  03301
New Hampshire Oncology - Hematology, PA - HooksettHooksett, New Hampshire  03106
Camino Medical Group - Treatment CenterMountain View, California  94040
Saint Helena HospitalSaint Helena, California  94574