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

Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP

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.

Study Overview

• Status: Terminated
• Conditions: Lymphoma
• Intervention / Treatment: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine

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.

• Study Type: Interventional
• Enrollment (Actual): 57
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • New York
    • Rochester, New York, United States, 14642
      • University of Rochester Medical Center - Wilmot Cancer Institute
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt-Ingram Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: R-CHOP; Patients will receive R-CHOP for 6 to 8 cycles: 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 Names: Rituxan; Drug: Cyclophosphamide; Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles; Other Names: Cytoxan; Drug: Doxorubicin; Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles; Other Names: Adriamycin; Drug: Prednisone; Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.; Other Names: Deltasone; Drug: Vincristine; Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles; Other Names: Oncovin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of a List of Genes and Construction of Survival Prediction Models That Will Predict Overall Survival at 30 Months in DLBCL Patients Receiving R-CHOP Therapy.	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.	30 months
Usefulness of Biomarkers Associated With Anti-Tumor Effects of Rituximab in Predicting Overall Survival in DLBCL Patients Receiving R-CHOP Therapy	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.	24 Months
Comparison of the Ability of Constructed Survival Models to Predict Overall Survival in DLBCL Patients Receiving R-CHOP Therapy	The investigators will compare the ability of constructed survival models to predict survival in DLBCL patients receiving R-CHOP therapy	2 Years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of the Ability of Models and/or Biomarkers Associated With Anti-Tumor Effects of Rituximab to Predict 24-month Time to Treatment Failure in DLBCL Patients Receiving R-CHOP Therapy	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.	24 Months
Overall Response Rate of Study Participants at the End of Protocol Therapy	Rate of participants achieving complete response (CR), complete response/unconfirmed (CRu) partial response (PR) according to Non-Hodgkin's Lymphoma response criteria.	Up to 8 cycles, about 24 weeks
Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies.	Number of participants from whom paraffin-embedded DLBCL tissue samples were collected for future studies.	Baseline

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Study Chair: Izidore S. Lossos, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2007
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2016

Study Registration Dates

• First Submitted: March 20, 2007
• First Submitted That Met QC Criteria: March 20, 2007
• First Posted (Estimate): March 22, 2007

Study Record Updates

• Last Update Posted (Actual): June 23, 2017
• Last Update Submitted That Met QC Criteria: June 2, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: stage III adult diffuse large cell lymphoma; stage IV adult diffuse large cell lymphoma; recurrent adult diffuse large cell lymphoma; noncontiguous stage II adult diffuse large cell lymphoma; contiguous stage II adult diffuse large cell lymphoma; stage I adult diffuse large cell lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Anti-Inflammatory Agents; Antirheumatic Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Alkylating; Alkylating Agents; Myeloablative Agonists; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Antineoplastic Agents, Immunological; Antibiotics, Antineoplastic; Cyclophosphamide; Rituximab; Prednisone; Doxorubicin; Vincristine
• Other Study ID Numbers: 20061138; SCCC-2006069 (Other Identifier: University of Miami Sylvester Comprehensive Cancer Center); WIRB-20070073 (Other Identifier: Western Institutional Review Board)