Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Non-Hodgkin's Lymphoma

Large B Cell Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00118209
• Other study ID #: CALGB-50303
• Secondary ID: CDR0000433265NCI
• Status: Completed
• Phase: Phase 3
• Start date: May 2005
• Est. completion date: November 15, 2021

Study information

• Verified date: November 2021
• Source: Alliance for Clinical Trials in Oncology
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This randomized phase III trial studies rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell non-Hodgkin's lymphoma. Monoclonal antibodies, such as rituximab, may block cancer growth in different ways by targeting certain cells. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving rituximab together with combination chemotherapy may kill more cancer cells. It is not yet known which combination chemotherapy regimen is more effective when given with rituximab in treating diffuse large B-cell non-Hodgkin's lymphoma.

PURPOSE: This randomized phase III trial is studying rituximab when given together with two different combination chemotherapy regimens to compare how well they work in treating patients with diffuse large B-cell lymphoma.

Description:

PRIMARY OBJECTIVES:

I. To compare the event-free survival of rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate, prednisone (R-CHOP) versus dose-adjusted (DA-) etoposide, prednisone, vincristine sulfate, doxorubicin hydrochloride, cyclophosphamide, and rituximab (EPOCH-R) chemotherapy in untreated cluster of differentiation (CD)20 positive (+) diffuse large B-cell lymphomas.

II. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling.

SECONDARY OBJECTIVES:

I. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R.

II. To define the pharmacogenomics of untreated diffuse large B-cell lymphoma (DLBCL) and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling.

III. To assess the use of molecular profiling for pathological diagnosis. IV. To identify new therapeutic targets using molecular profiling. V. To perform a comprehensive analysis of somatic alterations to the tumor genome and to understand which genomic alterations are somatically acquired by the tumor and which are encoded in the germ line of the patient.

VI. To identify biomarkers of response to chemotherapy by fludeoxyglucose F 18 (FDG)-positron emission tomography (PET)/computed tomography (CT) imaging that are predictive of histopathologic remissions and survival in patients with stage I (mediastinal), II, III, or IV untreated DLBCL.

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

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

IX. To establish a standardized protocol for FDG-PET/CT image acquisition. X. To determine additional FDG-PET/CT parameters (e.g., the ratio of tumor maximum standard uptake value [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.

XI. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

Other known NCT identifiers

• NCT00234351

Recruitment information / eligibility

• Status: Completed
• Enrollment: 524
• Est. completion date: November 15, 2021
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

1. Histologically documented de novo CD20+ DLBCL with stage II, III or IV disease.

• Stage I primary mediastinal (thymic) DLBCL is also eligible.

• Patients with an underlying low-grade lymphoma, such as a transformed lymphoma or low-grade lymphoma in the bone marrow, are not eligible.

• Diagnosis should be based on an adequate tissue sample, including open biopsy or core needle biopsy.

• Needle aspiration for primary diagnosis is unacceptable.

• Patients must have one of the following WHO classification subtypes:

• Diffuse large B-cell lymphoma (includes morphological variants:

centroblastic, immunoblastic, T-cell/histiocyte rich, and anaplastic)

• Mediastinal (thymic) large B-cell lymphoma

• Intravascular large B-cell lymphoma

• Note: Failure to submit a pathology block within 60 days of patient registration will be considered a major protocol violation.

• Fresh (frozen) tumor biopsy must be available or attempted. A frozen tumor biopsy equivalent to a minimum of four at least 16 gauge needle cores is an important component of this study.

• Patients without adequate frozen material should have a biopsy performed to obtain material.

• If a biopsy is performed and does not yield adequate material, the patient is still eligible for the study. If a biopsy cannot be done safely, the patient may still be eligible for the study if permission is granted.

• Note: This study does not allow concurrent radiation unless a patient has a documented CNS treatment failure with no systemic failure.

2. No prior cytotoxic chemotherapy or rituximab. Patients may be entered if they have received prior limited field radiation therapy or a short course of glucocorticoids (< 10 days) for an urgent local disease complication at diagnosis (e.g., cord compression, SVC syndrome). Patients who have received chemotherapy for prior malignancies are not eligible.

3. Age = 18 years

4. ECOG Performance Status 0-2

5. No active ischemic heart disease or congestive heart failure. If there is suspicion of cardiac disease, a cardiac ejection fraction must show LVEF > 45%, but the study is not required

6. No known lymphomatous involvement of the CNS. A lumbar puncture prior to study is not required in the absence of neurological symptoms

7. No known HIV disease. Patients with a history of intravenous drug abuse or any other behavior associated with an increased risk of HIV infection should be tested for exposure to the HIV virus. Patients who test positive or who are known to be infected are not eligible.

8. Non pregnant and non-nursing. Treatment would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective form of contraception.

9. Patients with active medical processes (e.g., uncontrolled bacterial or viral infection, bleeding) not related to their lymphoma should be excluded.

10. Required Initial Laboratory Values (unless non-Hodgkin lymphoma):

• ANC = 1000/µL

• Platelets = 100,000/µL

• Creatinine= 1.5 mg/dL or creatinine clearance = 50 cc/min

• Total Bilirubin = 2 mg/dL (unless a history of Gilbert's Disease)

Related Conditions & MeSH terms

• Large B Cell Lymphoma
• Lymphoma
• Lymphoma, B-Cell

Intervention

Biological:
• rituximab
IV

Drug:
• cyclophosphamide
IV
• doxorubicin
IV or CIVI
• vincristine
IV or CIVI
• prednisone
oral
• etoposide
CIVI
• filgrastim
IV
• pegfilgrastim
IV

Locations

Country	Name	City	State
United States	Alvin and Lois Lapidus Cancer Institute at Sinai Hospital	Baltimore	Maryland
United States	Mountainview Medical	Berlin	Vermont
United States	National Naval Medical Center	Bethesda	Maryland
United States	NIH - Warren Grant Magnuson Clinical Center	Bethesda	Maryland
United States	Mercy Cancer Center at Mercy Medical Center	Canton	Ohio
United States	Presbyterian Cancer Center at Presbyterian Hospital	Charlotte	North Carolina
United States	Creticos Cancer Center at Advocate Illinois Masonic Medical Center	Chicago	Illinois
United States	Robert H. Lurie Comprehensive Cancer Center at Northwestern University	Chicago	Illinois
United States	University of Illinois Cancer Center	Chicago	Illinois
United States	Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center	Columbus	Ohio
United States	New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care	Concord	New Hampshire
United States	Geisinger Cancer Institute at Geisinger Health	Danville	Pennsylvania
United States	Easton Regional Cancer Center at Easton Hospital	Easton	Pennsylvania
United States	Charles R. Wood Cancer Center at Glens Falls Hospital	Glens Falls	New York
United States	Altru Cancer Center at Altru Hospital	Grand Forks	North Dakota
United States	Geisinger Hazleton Cancer Center	Hazleton	Pennsylvania
United States	Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center	Hershey	Pennsylvania
United States	New Hampshire Oncology - Hematology, PA - Hooksett	Hooksett	New Hampshire
United States	Kinston Medical Specialists	Kinston	North Carolina
United States	Rebecca and John Moores UCSD Cancer Center	La Jolla	California
United States	Marshfield Clinic - Marshfield Center	Marshfield	Wisconsin
United States	Saint Joseph's Hospital	Marshfield	Wisconsin
United States	Cardinal Bernardin Cancer Center at Loyola University Medical Center	Maywood	Illinois
United States	Marshfield Clinic - Lakeland Center	Minocqua	Wisconsin
United States	Mary Babb Randolph Cancer Center at West Virginia University Hospitals	Morgantown	West Virginia
United States	Camino Medical Group - Treatment Center	Mountain View	California
United States	New York Weill Cornell Cancer Center at Cornell University	New York	New York
United States	CCOP - Christiana Care Health Services	Newark	Delaware
United States	Eastern Connecticut Hematology and Oncology Associates	Norwich	Connecticut
United States	Palo Alto Medical Foundation	Palo Alto	California
United States	Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Ministry Medical Group at Saint Mary's Hospital	Rhinelander	Wisconsin
United States	Marshfield Clinic - Indianhead Center	Rice Lake	Wisconsin
United States	Virginia Commonwealth University Massey Cancer Center	Richmond	Virginia
United States	James P. Wilmot Cancer Center at University of Rochester Medical Center	Rochester	New York
United States	Saint Helena Hospital	Saint Helena	California
United States	Christian Hospital Northeast-Northwest	Saint Louis	Missouri
United States	Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis	Saint Louis	Missouri
United States	Naval Medical Center - San Diego	San Diego	California
United States	Providence Cancer Institute at Providence Hospital - Southfield Campus	Southfield	Michigan
United States	Iredell Memorial Hospital	Statesville	North Carolina
United States	Marshfield Clinic at Saint Michael's Hospital	Stevens Point	Wisconsin
United States	Saint Michael's Hospital Cancer Center	Stevens Point	Wisconsin
United States	Madigan Army Medical Center - Tacoma	Tacoma	Washington
United States	Marshfield Clinic - Weston Center	Weston	Wisconsin
United States	Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center	Wilkes-Barre	Pennsylvania
United States	Wake Forest University Comprehensive Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Alliance for Clinical Trials in Oncology	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Whether the Gene Expression Signatures That Were Previously Associated With Survival Following CHOP Therapy Are Associated With Survival in Either of the Treatment Arms of the Prospective Trial		Up to 5 years post-registration
Primary	Progression-Free Survival Rate at 2 and 5 Years	Progression-free survival (PFS) is defined as the time from randomization to progression, relapse, or death from any cause, whichever occurred first. Progression (PD) or Relapse>; = 50% increase from nadir in the SPD of any previously identified abnormal node for PRs or nonresponders.>; Appearance of any new lesion during or after completion of therapy.>; PET+ is not a criterion for progressive disease. Patients only with PET+ findings must have evidence of progression on CT or biopsy proven.>; The PFS rate (percentage of participants who are alive and progression-free) at 2 and 5 years Kaplan Meier estimates and 95% Confidence Intervals are reported below.	Up to 5 years post-registration
Secondary	Response Rate	The overall response rate is defined as the percentage of participants with a response (Complete Response or Partial Response)	Up to 5 years post-registration
Secondary	Overall Survival Rate at 2 and 5 Years	Overall survival is defined as the time from randomization to death due to any cause. The overall survival (OS) rate (percentage of participants who are still alive) at 2 and 5 years Kaplan Meier estimates and 95% confidence intervals are reported below.	Up to 5 years post-registration