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

Primary Purpose

Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Rituximab
Cyclophosphamide
Doxorubicin
Prednisone
Vincristine
Sponsored by
University of Miami
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Lymphoma focused on measuring 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

Eligibility Criteria

18 Years - 120 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Stanford University
  • University of Miami
  • University of Rochester Medical Center - Wilmot Cancer Institute
  • Cleveland Clinic
  • Vanderbilt-Ingram Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

R-CHOP

Arm Description

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.

Outcomes

Primary Outcome Measures

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.
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.
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

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
March 20, 2007
Last Updated
June 2, 2017
Sponsor
University of Miami
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1. Study Identification

Unique Protocol Identification Number
NCT00450385
Brief Title
Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (R-CHOP)
Acronym
R-CHOP
Official Title
Phase II Study to Establish Gene Expression Models Predicting Survival of Diffuse Large B-Cell Lymphoma Patients Treated With R-CHOP
Study Type
Interventional

2. Study Status

Record Verification Date
May 2017
Overall Recruitment Status
Terminated
Why Stopped
Investigator Decision due to insufficient accrual.
Study Start Date
April 24, 2007 (Actual)
Primary Completion Date
May 2016 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Miami

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Lymphoma
Keywords
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
57 (Actual)

8. Arms, Groups, and Interventions

Arm Title
R-CHOP
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Rituximab
Other Intervention Name(s)
Rituxan
Intervention Description
Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cytoxan
Intervention Description
Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles
Intervention Type
Drug
Intervention Name(s)
Doxorubicin
Other Intervention Name(s)
Adriamycin
Intervention Description
Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles
Intervention Type
Drug
Intervention Name(s)
Prednisone
Other Intervention Name(s)
Deltasone
Intervention Description
Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Oncovin
Intervention Description
Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles
Primary Outcome Measure Information:
Title
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.
Description
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.
Time Frame
30 months
Title
Usefulness of Biomarkers Associated With Anti-Tumor Effects of Rituximab in Predicting Overall Survival in DLBCL Patients Receiving R-CHOP Therapy
Description
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.
Time Frame
24 Months
Title
Comparison of the Ability of Constructed Survival Models to Predict Overall Survival in DLBCL Patients Receiving R-CHOP Therapy
Description
The investigators will compare the ability of constructed survival models to predict survival in DLBCL patients receiving R-CHOP therapy
Time Frame
2 Years
Secondary Outcome Measure Information:
Title
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
Description
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.
Time Frame
24 Months
Title
Overall Response Rate of Study Participants at the End of Protocol Therapy
Description
Rate of participants achieving complete response (CR), complete response/unconfirmed (CRu) partial response (PR) according to Non-Hodgkin's Lymphoma response criteria.
Time Frame
Up to 8 cycles, about 24 weeks
Title
Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies.
Description
Number of participants from whom paraffin-embedded DLBCL tissue samples were collected for future studies.
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Izidore S. Lossos, MD
Organizational Affiliation
University of Miami
Official's Role
Study Chair
Facility Information:
Facility Name
Stanford University
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Rochester Medical Center - Wilmot Cancer Institute
City
Rochester
State/Province
New York
ZIP/Postal Code
14642
Country
United States
Facility Name
Cleveland Clinic
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Vanderbilt-Ingram Cancer Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Learn more about this trial

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

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