Clinical trial NCT00450385: Genes in Predicting Outcome of Patients With DLBCL Treated With Rituximab and Combination Chemotherapy (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
Overall status: TERMINATED
Phase: PHASE2
Conditions: 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
Lead sponsor: University of Miami
Sponsor class: OTHER
First posted: 2007-03-22
Enrollment: 57
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: 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.
timeFrame: 30 months
measure: Usefulness of Biomarkers Associated With Anti-Tumor Effects of Rituximab in Predicting Overall Survival in DLBCL Patients Receiving R-CHOP Therapy
timeFrame: 24 Months
measure: Comparison of the Ability of Constructed Survival Models to Predict Overall Survival in DLBCL Patients Receiving R-CHOP Therapy
timeFrame: 2 Years
Secondary outcomes:
measure: 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
timeFrame: 24 Months
measure: Overall Response Rate of Study Participants at the End of Protocol Therapy
timeFrame: Up to 8 cycles, about 24 weeks
measure: Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies.
timeFrame: Baseline
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford University
state: California
city: Miami
country: United States
facility: University of Miami
state: Florida
city: Rochester
country: United States
facility: University of Rochester Medical Center - Wilmot Cancer Institute
state: New York
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Nashville
country: United States
facility: Vanderbilt-Ingram Cancer Center
state: Tennessee
Study officials:
affiliation: University of Miami
name: Izidore S. Lossos, MD
role: STUDY_CHAIR
References: