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

Phase 2

Terminated

• Conditions: Lymphoma
• Interventions: Drug: Rituximab; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Prednisone; Drug: Vincristine

• Registration Number: NCT00450385
• Lead Sponsor: University of Miami

Brief Summary

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.

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 Timeline

• Study First Submitted: 2007-03-20
• Study First Submitted QC: 2007-03-20
• Study First Posted: 2007-03-22
• Study Start: 2007-04-24
• Primary Completion: 2016-05
• Study Completion: 2016-05
• Results First Submitted: 2017-03-13
• Status Verified: 2017-05
• Results First Submitted QC: 2017-06-02
• Last Update Submitted: 2017-06-02
• Results First Posted: 2017-06-23
• Last Update Posted: 2017-06-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 57

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
R-CHOP	Doxorubicin	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.
R-CHOP	Rituximab	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.
R-CHOP	Cyclophosphamide	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.
R-CHOP	Prednisone	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.
R-CHOP	Vincristine	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.

Primary Outcome Measures

Name	Time	Method
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.	30 months	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.
Usefulness of Biomarkers Associated With Anti-Tumor Effects of Rituximab in Predicting Overall Survival in DLBCL Patients Receiving R-CHOP Therapy	24 Months	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.
Comparison of the Ability of Constructed Survival Models to Predict Overall Survival in DLBCL Patients Receiving R-CHOP Therapy	2 Years	The investigators will compare the ability of constructed survival models to predict survival in DLBCL patients receiving R-CHOP therapy

Secondary Outcome Measures

Name	Time	Method
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	24 Months	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 at the End of Protocol Therapy	Up to 8 cycles, about 24 weeks	Rate of participants achieving complete response (CR), complete response/unconfirmed (CRu) partial response (PR) according to Non-Hodgkin's Lymphoma response criteria.
Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies.	Baseline	Number of participants from whom paraffin-embedded DLBCL tissue samples were collected for future studies.

Trial Locations

Locations (5)

Stanford University; 🇺🇸 Stanford, California, United States

University of Rochester Medical Center - Wilmot Cancer Institute; 🇺🇸 Rochester, New York, United States

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States

Vanderbilt-Ingram Cancer Center; 🇺🇸 Nashville, Tennessee, United States

University of Miami; 🇺🇸 Miami, Florida, United States