Genes in Predicting Outcome of Patients With Diffuse Large B-Cell Lymphoma Treated With Rituximab and Combination Chemotherapy

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2014 by University of Miami
Sponsor:
Information provided by (Responsible Party):
Izidore Lossos, University of Miami
ClinicalTrials.gov Identifier:
NCT00450385
First received: March 20, 2007
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about changes that occur in DNA and identify biomarkers related to cancer. It may also help doctors predict how patients respond to treatment.

PURPOSE: This phase II trial is studying how well genes and biomarkers predict outcome of patients with diffuse large B-cell lymphoma treated with rituximab and combination chemotherapy.


Condition Intervention Phase
Lymphoma
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Prednisone
Drug: Vincristine
Genetic: RNA-based gene array studies
Genetic: Real time PCR gene expression studies
Genetic: Tissue-array immunohistochemical studies
Genetic: Immunoglobulin G Fc receptor genotypes determination
Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP

Resource links provided by NLM:


Further study details as provided by University of Miami:

Primary Outcome Measures:
  • Overall survival at 30 months [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • Biomarkers (immunoglobulin G Fc receptor genotypes, CD20 protein expression, and gene expression profiles) [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • Overall response [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • Progression-free survival [ Time Frame: At study completion ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to treatment failure [ Time Frame: At study completion ] [ Designated as safety issue: No ]
  • Response (complete response [CR], CR unconfirmed, partial response) [ Time Frame: At study completion ] [ Designated as safety issue: No ]

Estimated Enrollment: 213
Study Start Date: February 2007
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-CHOP Drug: Rituximab
Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles
Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles
Drug: Doxorubicin
Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles
Drug: Prednisone
Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.
Drug: Vincristine
Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles
Genetic: RNA-based gene array studies
Diagnostic tumor tissue sample
Genetic: Real time PCR gene expression studies
Diagnostic tumor tissue sample
Genetic: Tissue-array immunohistochemical studies
Diagnostic tumor tissue sample
Genetic: Immunoglobulin G Fc receptor genotypes determination
Diagnostic tumor tissue sample

Detailed Description:

OBJECTIVES:

Primary

  • Determine a list of genes and construct a survival prediction model(s) that will predict the overall survival at 30 months of patients with diffuse large B-cell lymphoma treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisone.
  • Determine the usefulness of biomarkers associated with the antitumor effects of rituximab (e.g., immunoglobulin G Fc receptor genotypes, CD20 protein expression, and gene expression profiles) in predicting overall survival of patients treated with this regimen.
  • Compare the ability of constructed survival models to predict survival of these patients.

Secondary

  • Determine the ability of the models and/or biomarkers associated with the antitumor effects of rituximab to predict 24-month time to treatment failure, defined as disease progression, death, or initiation of new treatment.
  • Determine the overall response rate (complete and partial response rate) at the end of study therapy.
  • Collect a series of fixed tissue samples with annotated clinical information and state of the art therapy for future studies.

OUTLINE: This is a prospective study.

Patients will receive 6 cycles of R-CHOP therapy.

Paraffin-embedded tissue blocks and immunohistochemical slides are collected at baseline for RNA-based gene array studies, real-time polymerase chain reaction gene expression studies, polymorphism analysis, tissue-array immunohistochemical studies, and immunoglobulin G Fc receptor genotypes determination.

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

PROJECTED ACCRUAL: A total of 123 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Diagnosis of diffuse large B-cell lymphoma, meeting 1 of the following staging criteria:

    • Limited stage I disease that is bulky (i.e., more than 10 cm) or with International Prognostic Index > 1
    • Stage II-IV disease
  • CD20-positive disease
  • Paraffin-embedded tumor specimen must be available
  • No active CNS lymphoma

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-3
  • WBC > 2,500/mm³
  • Absolute neutrophil count > 1,000/mm³ (unless due to disease in marrow)
  • Platelet count > 100,000/mm³ (unless due to disease in marrow)
  • Creatinine < 2.0 mg/dL
  • Bilirubin < 1.5 mg/dL (1.5-3.0 mg/dL if due to liver involvement by lymphoma)
  • AST and ALT < 3 times upper limit of normal
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • LVEF > 45%
  • No HIV positivity
  • No other malignancy except for basal cell carcinoma of the skin or in situ carcinoma of the cervix (unless the tumor was treated with curative intent ≥ 2 years ago and the patient continues to be free of evidence of recurrence)

PRIOR CONCURRENT THERAPY:

  • No prior chemotherapy, radiotherapy, or immunotherapy

    • A prior short course (i.e., < 2 weeks) of corticosteroids allowed
  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: NCT00450385

Locations
United States, California
Stanford University Recruiting
Stanford, California, United States, 94305
Contact: Ash A Alizadeh, MD/PhD    650-725-0120    arasha@stanford.edu   
Principal Investigator: Ash A Alizadeh, MD/PhD         
United States, Florida
University of Miami Sylvester Comprehensive Cancer Center - Miami Recruiting
Miami, Florida, United States, 33136
Contact: University of Miami Sylvester Comprehensive Cancer Center Clin    866-574-5124    Sylvester@emergingmed.com   
Sponsors and Collaborators
University of Miami
Investigators
Study Chair: Izidore S. Lossos, MD University of Miami Sylvester Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided

Responsible Party: Izidore Lossos, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT00450385     History of Changes
Other Study ID Numbers: 20061138, SCCC-2006069, WIRB-20070073
Study First Received: March 20, 2007
Last Updated: August 7, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Miami:
recurrent adult diffuse large cell lymphoma
stage III adult diffuse large cell lymphoma
stage IV adult diffuse large cell lymphoma
contiguous stage II adult diffuse large cell lymphoma
noncontiguous stage II adult diffuse large cell lymphoma
stage I adult diffuse large cell lymphoma

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
Immunoglobulin G
Immunoglobulins
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

ClinicalTrials.gov processed this record on October 22, 2014