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

University of Miami

Status and phase: Terminated; Phase 2

Conditions: Lymphoma

Treatments: Drug: Doxorubicin; Drug: Prednisone; Drug: Rituximab; Drug: Cyclophosphamide; Drug: Vincristine

Study type: Interventional

Funder types: Other

Identifiers

NCT00450385

WIRB-20070073 (Other Identifier)

SCCC-2006069 (Other Identifier)

20061138

Details and patient eligibility

About

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.

Full 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.

Enrollment: 57 patients

Sex: All

Ages: 18 to 120 years old

Volunteers: No 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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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57 participants in 1 patient group

R-CHOP

Experimental group

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.

Treatment:

Drug: Vincristine

Drug: Cyclophosphamide

Drug: Rituximab

Drug: Prednisone

Drug: Doxorubicin