Lymphoma
Conditions
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
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.
Interventions
DRUGRituximab
Rituximab 375 mg/m2 on day 1 for 6 to 8 cycles
DRUGCyclophosphamide
Cyclophosphamide 750 mg/m2 IV on day 1 for 6 to 8 cycles
DRUGDoxorubicin
Doxorubicin 50 mg/m2 on day 1 for 6 to 8 cycles
DRUGPrednisone
Prednisone 40 mg/m2 orally days 1-5, repeated every 21 days for 6 to 8 cycles.
DRUGVincristine
Vincristine 1.4 mg/m2 (maximum = 2 mg) IV on day 1 for 6 to 8 cycles
Sponsors
University of Miami
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 60 patients were consented, however, only 57 of these patients were found to be eligible for enrollment per the protocol.
Participants by arm
| Arm | Count |
|---|---|
| R-CHOP 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. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 1 |
| Overall Study | Death | 3 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Other | 3 |
| Overall Study | Physician Decision | 1 |
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | R-CHOP |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 32 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Region of Enrollment United States | 57 Participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 57 |
| other Total, other adverse events | 3 / 57 |
| serious Total, serious adverse events | 4 / 57 |
Outcome results
Primary
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
Time frame: 2 Years
Population: The comparison could not be made because the study required a minimum of 90 participants for initial gene expression analyses from which survival prediction model(s) would be derived. Due to actual participant accrual (57) being far below the minimum number of participants required, no gene expression or survival prediction data were collected.
Primary
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.
Time frame: 30 months
Population: The study required a minimum of 90 participants for gene expression analyses from which survival prediction model(s) could be derived. Due to actual participant accrual (57) being far below the minimum number of participants required, no data were collected on gene expression, and no survival prediction models were constructed.
Primary
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.
Time frame: 24 Months
Population: The study required a minimum of 90 participants for associated biomarker analyses. Due to actual participant accrual (57) being far below the minimum number of participants required, no biomarker data were collected.
Secondary
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.
Time frame: 24 Months
Population: The determination could not be made because the study required a minimum of 90 participants for biomarker analyses and derivation of survival prediction model(s). Due to actual participant accrual (57) being far below the minimum required, no data were collected on the ability of models and/or biomarkers to predict time to treatment failure.
Secondary
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.
Time frame: Baseline
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| R-CHOP | Number of Participants From Whom Fixed Tissue Samples Were Collected for Future Studies. | 57 Participants |
Secondary
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.
Time frame: Up to 8 cycles, about 24 weeks
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| R-CHOP | Overall Response Rate of Study Participants at the End of Protocol Therapy | Complete Response (CR) | 40 Participants |
| R-CHOP | Overall Response Rate of Study Participants at the End of Protocol Therapy | Complete Response unconfirmed (CRu) | 0 Participants |
| R-CHOP | Overall Response Rate of Study Participants at the End of Protocol Therapy | Partial Response (PR) | 7 Participants |
| R-CHOP | Overall Response Rate of Study Participants at the End of Protocol Therapy | Progressive Disease (PD) | 2 Participants |
| R-CHOP | Overall Response Rate of Study Participants at the End of Protocol Therapy | Unknown | 8 Participants |