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

Lymphoma Clinical Trial

— 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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00450385
• Other study ID #: 20061138
• Secondary ID: SCCC-2006069WIRB
• Status: Terminated
• Phase: Phase 2
• First received: March 20, 2007
• Last updated: June 1, 2016
• Start date: February 2007
• Est. completion date: May 2016

Study information

• Verified date: June 2016
• Source: University of Miami
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 59
• Est. completion date: May 2016
• Est. primary completion date: May 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 120 Years

Eligibility

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

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma

Intervention

Drug:
• Rituximab
Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles
• Cyclophosphamide
Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles
• Doxorubicin
Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles
• Prednisone
Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.
• Vincristine
Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles

Genetic:
• Lymphoma Tissue Specimen
Diagnostic Lymphoma Tissue specimen for gene expression analysis taken at Baseline. The following correlative studies will be performed: 1. RNA-based gene array studies 2. Real time polymerase chain reaction (PCR) gene expression studies 3. Tissue-array immunohistochemical studies 4. Immunoglobulin G Fc receptor genotypes determination

Locations

Country	Name	City	State
United States	University of Miami	Miami	Florida
United States	Stanford University	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
University of Miami

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Estimated Rate of 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	No
Primary	Estimated Rate of Overall Survival at 24-Months 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. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.	24 Months	No
Primary	Estimated Overall Survival Rate in DLBCL Patients Receiving R-CHOP Therapy	The investigators will compare the ability of constructed survival models to predict survival in DLBCL. Overall survival time will be calculated from the date of the diagnosis until death or last follow-up examination.	2 Years	No
Secondary	Estimated 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	No
Secondary	Overall Response Rate of Study Participants to Protocol Therapy	Rate of participants achieving complete response (CR), complete response/unconfirmed (CRu) partial response (PR) according to Non-Hodgkin's Lymphoma response criteria.	2 Years	No