Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (R-CHOP) (R-CHOP)

This study has been terminated.
(Investigator Decision due to insufficient accrual.)
Sponsor:
Information provided by (Responsible Party):
Izidore Lossos, University of Miami
ClinicalTrials.gov Identifier:
NCT00450385
First received: March 20, 2007
Last updated: June 1, 2016
Last verified: June 2016
  Purpose
The investigators hypothesize that survival of newly diagnosed DLBCL (diffuse large B-cell lymphoma) patients treated with R-CHOP can be predicted by RNA or protein gene expression or by presence of biomarkers associated with the anti-tumor effects of Rituximab.

Condition Intervention Phase
Lymphoma
Drug: Rituximab
Drug: Cyclophosphamide
Drug: Doxorubicin
Drug: Prednisone
Drug: Vincristine
Genetic: Lymphoma Tissue Specimen
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:
  • Estimated Rate of Overall Survival at 30 Months in DLBCL Patients Receiving R-CHOP Therapy. [ Time Frame: 30 months ] [ Designated as safety issue: No ]
    The investigators aim to determine a list of genes and construct survival prediction model(s) that will predict the overall survival at 30 months in DLBCL patients prospectively treated with R-CHOP chemotherapy. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.

  • Estimated Rate of Overall Survival at 24-Months in DLBCL Patients receiving R-CHOP Therapy [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    The investigators aim to determine the usefulness of biomarkers associated with the antitumor effects of rituximab (e.g. immunoglobulin GFc receptor genotypes, CD20 protein expression and gene expression profiles) to predict overall survival of DLBCL patients treated with R-CHOP therapy and followed for at least 24 months or until death. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.

  • Estimated Overall Survival Rate in DLBCL Patients Receiving R-CHOP Therapy [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    The investigators will compare the ability of constructed survival models to predict survival in DLBCL. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.


Secondary Outcome Measures:
  • Estimated Time to Treatment Failure in DLBCL Patients Receiving R-CHOP Therapy [ Time Frame: 24 Months ] [ Designated as safety issue: No ]
    The investigators aim to determine the ability of the models and/or biomarkers associated with the anti-tumor effects of rituximab to predict 24-month time to treatment failure, defined as disease progression, death or initiation of new treatment.

  • Overall Response Rate of Study Participants to Protocol Therapy [ Time Frame: 2 Years ] [ Designated as safety issue: No ]
    Rate of participants achieving complete response (CR), complete response/unconfirmed (CRu) partial response (PR) according to Non-Hodgkin's Lymphoma response criteria.


Enrollment: 59
Study Start Date: February 2007
Study Completion Date: May 2016
Primary Completion Date: May 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: R-CHOP

Patients will receive R-CHOP:

  • Rituximab 375 mg/m2 on day 1
  • Cyclophosphamide 750 mg/m2 IV on day 1
  • Doxorubicin 50 mg/m2 on day 1
  • Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1
  • Prednisone 100 mg orally days 1-5, repeated every 21 days.
Drug: Rituximab
Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles
Other Name: Rituxan
Drug: Cyclophosphamide
Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles
Other Name: Cytoxan
Drug: Doxorubicin
Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles
Other Name: Adriamycin
Drug: Prednisone
Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.
Other Name: Deltasone
Drug: Vincristine
Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles
Other Name: Oncovin
Genetic: Lymphoma Tissue Specimen

Diagnostic Lymphoma Tissue specimen for gene expression analysis taken at Baseline. The following correlative studies will be performed:

  • 1. RNA-based gene array studies
  • 2. Real time polymerase chain reaction (PCR) gene expression studies
  • 3. Tissue-array immunohistochemical studies
  • 4. Immunoglobulin G Fc receptor genotypes determination

Detailed Description:
In this phase II multi-institutional trial, the investigators will identify genes associated with either good or bad outcome in DLBCL patients treated with R-CHOP, will construct a robust predictive models based on RNA extracted from or paraffin specimens as well on immunohistochemistry and will examine the predictive power of new biomarkers associated with the anti-tumor effects of rituximab. The acquisition of fixed tissue as a component of this uniformly treated prospective study will also afford future studies with this informative dataset.
  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 1. Diagnosis of diffuse large B-cell lymphoma, CD20-positive, according to the World Health Organization Classification, stages II-IV or limited stage I disease that is bulky (more than 10 cm) or with International Prognostic Index (IPI) score > 1.
  • 2. Patients must not have had prior chemotherapy, radiotherapy or immunotherapy. A short course (< 2 weeks) of corticosteroids is allowed.
  • 3. Adequate paraffin-embedded tumor specimen must be available for gene expression analysis and immunohistochemistry prior to initiation of therapy. (If the specimen is deemed inadequate, the subject can be retroactively screen failed, as this does not change the treatment regimen).
  • 4. Baseline measurements and evaluation must be obtained within 4 weeks before first treatment.
  • 5. Age >18 years.
  • 6. Eastern Cooperative Oncology Group (ECOG) performance status 0-3.
  • 7. Adequate organ function:

    • White Blood Cells count (WBC) >2500/µL
    • Absolute Neutrophil Count (ANC) > 1000/µL (unless due to disease in marrow)
    • platelet count >100,000/µL (unless due to disease in marrow)
    • creatinine < 2.0 mg/dL,
    • bilirubin < 1.5 mg/dL (may be 1.5-3.0 mg/dl if due to liver involvement by lymphoma)
    • Serum Glutamic Oxaloacetic Transaminase (SGOT)/ Serum Glutamic Pyruvic Transaminase (SGPT) <3 x upper limit of normal.
  • 8. Female patients must not be pregnant or breast feeding.
  • 9. Women of childbearing potential and men must be strongly advised to use an accepted and effective method of contraception.
  • 10. Patients must have left ventricular ejection fraction of >45%.
  • 11. Provision of written informed consent.

Exclusion Criteria:

  • 1. Patients with a second malignancy other than basal cell carcinoma of the skin or in situ carcinoma of the cervix unless the tumor was treated with curative intent at least two years previously; and; the patient continue to be free of evidence of recurrence.
  • 2. Patients with HIV infection as these patients are managed on dedicated protocols.
  • 3. Patients with active central nervous system (CNS) lymphoma.
  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
Stanford, California, United States, 94305
United States, Florida
University of Miami
Miami, Florida, United States, 33136
Sponsors and Collaborators
University of Miami
Investigators
Study Chair: Izidore S. Lossos, MD University of Miami
  More Information

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: June 1, 2016
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
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Cyclophosphamide
Rituximab
Liposomal doxorubicin
Doxorubicin
Prednisone
Vincristine
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 28, 2016