Rituximab and Combination Chemotherapy in Treating Patients With Diffuse Large B-Cell Lymphoma

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier:
NCT00118209
First received: July 8, 2005
Last updated: March 19, 2015
Last verified: March 2015
  Purpose

RATIONALE: Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. 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 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.


Condition Intervention Phase
Large B Cell Lymphoma
Biological: rituximab
Drug: cyclophosphamide
Drug: doxorubicin
Drug: vincristine
Drug: prednisone
Drug: etoposide
Drug: filgrastim
Drug: pegfilgrastim
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Alliance for Clinical Trials in Oncology:

Primary Outcome Measures:
  • Event-free survival [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Response rate [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]
  • Toxicity [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: Yes ]
  • 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 [ Time Frame: Up to 5 years post-registration ] [ Designated as safety issue: No ]

Enrollment: 524
Study Start Date: May 2005
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Arm A - R-CHOP

Patients receive the following treatment:

  • Rituximab 375 mg/m^2 IV infusion on Day 1 prior to CHOP chemotherapy
  • Cyclophosphamide 750 mg/m^2 IV on Day 1
  • Doxorubicin 50 mg/m^2 IV on Day 1
  • Vincristine 1.4 mg/m^2 IV (2 mg cap) on Day 1
  • Prednisone 40 mg/m^2/day PO on Days 1-5
  • filgrastim or pegfilgrastim as defined in the protocol

Required ancillary medications is administered during all cycles as defined in the protocol.

Cycles will be repeated every 21 days for 6 treatment cycles. Restaging will occur after Cycles 4 and 6.

Biological: rituximab
IV
Drug: cyclophosphamide
IV
Drug: doxorubicin
IV or CIVI
Drug: vincristine
IV or CIVI
Drug: prednisone
oral
Drug: filgrastim
IV
Drug: pegfilgrastim
IV
Experimental: Arm B - DA-EPOCH-R

Patients receive the following treatment:

Cycle 1 Doses:

  • Rituximab 375 mg/m^2 IV infusion on Day 1 prior to EPOCH chemotherapy
  • Doxorubicin 10 mg/m^2/day CIVI on Days 1-4
  • Etoposide 50 mg/m^2/day CIVI on Days 1-4
  • Vincristine 0.4 mg/m^2/day (no cap) CIVI on Days 1-4 (total 1.6 mg/m2 over 96 hours)
  • Cyclophosphamide 750 mg/m^2 IV on Day 5 (following completion of 96 hour infusions)
  • Prednisone 60 mg/m^2 PO BID on Days 1-5
  • Administer filgrastim 480 mcg subcutaneous daily from Day 6 until ANC > 5000 after the nadir (nadir usually between Days 10-12) or for 10 days (Days 6-15) if the ANC is not being monitored, during every cycle.

Doses for subsequent cycles will be determined by the absolute neutrophil (ANC) or platelet nadir from the previous cycle.

Required ancillary medications are administered during all cycles as defined in the protocol.

Cycles will be repeated every 21 days for a maximum of 6 cycles. Restaging will occur after Cycles 4 and 6.

Biological: rituximab
IV
Drug: cyclophosphamide
IV
Drug: doxorubicin
IV or CIVI
Drug: vincristine
IV or CIVI
Drug: prednisone
oral
Drug: etoposide
CIVI
Drug: filgrastim
IV

Detailed Description:

Objectives:

  1. Primary Objectives:

    1. To compare the event-free survival of R-CHOP versus DA-EPOCH-R chemotherapy in untreated CD20+ diffuse large B-cell lymphomas
    2. To develop a molecular predictor of outcome of R-CHOP and DA-EPOCH-R chemotherapy using molecular profiling
  2. Secondary Objectives:

    1. To compare the response rates, overall survival and toxicity of R-CHOP versus DA-EPOCH-R
    2. To define the pharmacogenomics of untreated DLBCL and correlate clinical parameters (toxicity, response, survival outcomes and laboratory results) with molecular profiling
    3. To assess the use of molecular profiling for pathological diagnosis
    4. To identify new therapeutic targets using molecular profiling
    5. 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
    6. To 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
    7. 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
    8. To determine whether FDG-PET/CT measurements of tumor response after the second cycle of chemotherapy can predict clinical response
    9. To establish a standardized protocol for FDG-PET/CT image acquisition
    10. To 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
    11. To evaluate inter-institutional reproducibility of FDG-PET/CT measurements for this indication

After patients have completed treatment on this study, all patients will be asked to return to the clinic for follow-up exams every three months for the first two years, and then every six months thereafter for three years. A total of five years from study registration.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  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)
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00118209

  Hide Study Locations
Locations
United States, California
Rebecca and John Moores UCSD Cancer Center
La Jolla, California, United States, 92093-0658
Camino Medical Group - Treatment Center
Mountain View, California, United States, 94040
Palo Alto Medical Foundation
Palo Alto, California, United States, 94301
Saint Helena Hospital
Saint Helena, California, United States, 94574
Naval Medical Center - San Diego
San Diego, California, United States, 92134
United States, Connecticut
Eastern Connecticut Hematology and Oncology Associates
Norwich, Connecticut, United States, 06360
United States, Delaware
CCOP - Christiana Care Health Services
Newark, Delaware, United States, 19713
United States, Illinois
University of Illinois Cancer Center
Chicago, Illinois, United States, 60612-7243
Robert H. Lurie Comprehensive Cancer Center at Northwestern University
Chicago, Illinois, United States, 60611-3013
Creticos Cancer Center at Advocate Illinois Masonic Medical Center
Chicago, Illinois, United States, 60657
Cardinal Bernardin Cancer Center at Loyola University Medical Center
Maywood, Illinois, United States, 60153
United States, Maryland
Alvin and Lois Lapidus Cancer Institute at Sinai Hospital
Baltimore, Maryland, United States, 21215
NIH - Warren Grant Magnuson Clinical Center
Bethesda, Maryland, United States, 20892-1182
National Naval Medical Center
Bethesda, Maryland, United States, 20889-5600
United States, Michigan
Providence Cancer Institute at Providence Hospital - Southfield Campus
Southfield, Michigan, United States, 48075
United States, Missouri
Christian Hospital Northeast-Northwest
Saint Louis, Missouri, United States, 63136
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
Saint Louis, Missouri, United States, 63110
United States, New Hampshire
New Hampshire Oncology - Hematology, PA at Payson Center for Cancer Care
Concord, New Hampshire, United States, 03301
New Hampshire Oncology - Hematology, PA - Hooksett
Hooksett, New Hampshire, United States, 03106
United States, New York
Charles R. Wood Cancer Center at Glens Falls Hospital
Glens Falls, New York, United States, 12801
New York Weill Cornell Cancer Center at Cornell University
New York, New York, United States, 10021
James P. Wilmot Cancer Center at University of Rochester Medical Center
Rochester, New York, United States, 14642
United States, North Carolina
Presbyterian Cancer Center at Presbyterian Hospital
Charlotte, North Carolina, United States, 28233-3549
Kinston Medical Specialists
Kinston, North Carolina, United States, 28501
Iredell Memorial Hospital
Statesville, North Carolina, United States, 28677
Wake Forest University Comprehensive Cancer Center
Winston-Salem, North Carolina, United States, 27157-1096
United States, North Dakota
Altru Cancer Center at Altru Hospital
Grand Forks, North Dakota, United States, 58201
United States, Ohio
Mercy Cancer Center at Mercy Medical Center
Canton, Ohio, United States, 44708
Arthur G. James Cancer Hospital and Richard J. Solove Research Institute at Ohio State University Comprehensive Cancer Center
Columbus, Ohio, United States, 43210-1240
United States, Pennsylvania
Geisinger Cancer Institute at Geisinger Health
Danville, Pennsylvania, United States, 17822-0001
Easton Regional Cancer Center at Easton Hospital
Easton, Pennsylvania, United States, 18042
Geisinger Hazleton Cancer Center
Hazleton, Pennsylvania, United States, 18201
Penn State Hershey Cancer Institute at Milton S. Hershey Medical Center
Hershey, Pennsylvania, United States, 17033-0850
Western Pennsylvania Cancer Institute at Western Pennsylvania Hospital
Pittsburgh, Pennsylvania, United States, 15224-1791
Frank M. and Dorothea Henry Cancer Center at Geisinger Wyoming Valley Medical Center
Wilkes-Barre, Pennsylvania, United States, 18711
United States, Vermont
Mountainview Medical
Berlin, Vermont, United States, 05602
United States, Virginia
Virginia Commonwealth University Massey Cancer Center
Richmond, Virginia, United States, 23298-0037
United States, Washington
Madigan Army Medical Center - Tacoma
Tacoma, Washington, United States, 98431
United States, West Virginia
Mary Babb Randolph Cancer Center at West Virginia University Hospitals
Morgantown, West Virginia, United States, 26506
United States, Wisconsin
Marshfield Clinic - Marshfield Center
Marshfield, Wisconsin, United States, 54449
Saint Joseph's Hospital
Marshfield, Wisconsin, United States, 54449
Marshfield Clinic - Lakeland Center
Minocqua, Wisconsin, United States, 54548
Ministry Medical Group at Saint Mary's Hospital
Rhinelander, Wisconsin, United States, 54501
Marshfield Clinic - Indianhead Center
Rice Lake, Wisconsin, United States, 54868
Marshfield Clinic at Saint Michael's Hospital
Stevens Point, Wisconsin, United States, 54481
Saint Michael's Hospital Cancer Center
Stevens Point, Wisconsin, United States, 54481
Marshfield Clinic - Weston Center
Weston, Wisconsin, United States, 54476
Sponsors and Collaborators
Alliance for Clinical Trials in Oncology
Investigators
Study Chair: Wyndham H. Wilson, MD, PhD National Cancer Institute (NCI)
Study Chair: Andrew D. Zelenetz, MD, PhD Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
No publications provided by Alliance for Clinical Trials in Oncology

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alliance for Clinical Trials in Oncology
ClinicalTrials.gov Identifier: NCT00118209     History of Changes
Obsolete Identifiers: NCT00234351
Other Study ID Numbers: CALGB-50303, CDR0000433265, NCI-2009-00480, U10CA031946, U10CA180821
Study First Received: July 8, 2005
Last Updated: March 19, 2015
Health Authority: United States: NCI Central Institutional Review Board

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Cyclophosphamide
Doxorubicin
Liposomal doxorubicin
Prednisone
Rituximab
Vincristine
Alkylating Agents
Anti-Inflammatory Agents
Antibiotics, Antineoplastic
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Alkylating
Antineoplastic Agents, Hormonal
Antineoplastic Agents, Phytogenic
Antirheumatic Agents
Enzyme Inhibitors
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Immunologic Factors

ClinicalTrials.gov processed this record on July 01, 2015