Tailored Prednisone Reduction in Preventing Hyperglycemia in Participants With B-Cell Non-Hodgkin Lymphoma Receiving Combination Chemotherapy Treatment

Study Overview
=================
Brief Summary
-----------------
This phase II trial studies how well tailored prednisone reduction works in preventing hyperglycemia in participants with B-cell non-Hodgkin lymphoma receiving combination chemotherapy treatment. Drugs used in chemotherapy, such as rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Reductions in prednisone dose may lower blood sugar levels.

Detailed Description
-----------------
PRIMARY OBJECTIVES: I. To compare the cumulative incidence of hyperglycemia after 3 cycles of treatment between standard or tailored rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) chemotherapy. SECONDARY OBJECTIVES: I. To compare the cumulative incidence of hyperglycemia after 6 cycles of treatment and at 6 months post-treatment between standard or tailored R-CHOP chemotherapy. II. To compare response rates after 6 cycles of treatment as measured by Cheson's criteria between standard or tailored R-CHOP chemotherapy. III. To compare cumulative rates of grade III or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) criteria between standard or tailored R-CHOP chemotherapy from cycle 1 through cycle 6. IV. To compare severity of prednisone related adverse events using the Patient Reported Outcome (PRO)-CTCAE form between standard or tailored R-CHOP chemotherapy from cycle 1 through cycle 6. V. To compare health related quality of life (HRQOL) between standard or tailored R-CHOP chemotherapy at baseline, cycle 4 day 1 and after cycle 6. EXPLORATORY OBJECTIVES: I. To evaluate the alternative glucose measures of fasting blood glucose (FBG), hemoglobin A1c (HbA1c), fasting insulin and fructosamine to estimate hyperglycemia. II. To compare health related quality of life (HRQOL) in those with and without hyperglycemia after 3 cycles, 6 cycles, and 6 months post R-CHOP chemotherapy. III. To compare glycemic variability between the standard and tailored prednisone arms at day 1 of each cycle IV. To determine the ability of patients in the standard or tailored prednisone R-CHOP groups to complete all six cycles of chemotherapy. OUTLINE: Participants are randomized to 1 of 2 arms. ARM I: Participants receive rituximab intravenously (IV), vincristine sulfate IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Participants also receive tailored prednisone dose orally (PO) once daily (QD) on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. ARM II: Participants receive rituximab, vincristine sulfate doxorubicin hydrochloride, and cyclophosphamide as in Arm I. Participants also receive usual care prednisone dose PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study treatment, participants are followed up to 5 years.

Official Title
-----------------
A Randomized Phase II Pilot of Tailored Prednisone Reduction Versus Usual Care for the Treatment of Hyperglycemia During R-CHOP Chemotherapy

Conditions
-----------------
B-Cell Non-Hodgkin Lymphoma

Intervention / Treatment
-----------------
* Drug: Cyclophosphamide
* Drug: Doxorubicin Hydrochloride
* Other: Laboratory Biomarker Analysis
* Drug: Prednisone
* Other: Quality-of-Life Assessment
* Other: Questionnaire Administration
* Biological: Rituximab
* Drug: Vincristine Sulfate


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of B cell non-Hodgkin lymphoma confirmed by World Health Organization (WHO) criteria Planned treatment with R-CHOP chemotherapy Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3 Life expectancy of greater than 3 months with chemotherapy Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately Ability to understand and the willingness to sign an Institutional Review Board (IRB)-approved informed consent document (either directly or via a legally authorized representative) Exclusion Criteria: Uncontrolled human immunodeficiency virus (HIV), CD4 count < 50 Diagnosis of primary central nervous system (CNS) lymphoma Unable to receive R-CHOP chemotherapy History of severe (i.e. anaphylactic) allergic reactions attributed to compounds of similar chemical or biologic composition to glucocorticoids and other component of R- Uncontrolled intercurrent illness including, but not limited to ongoing or active infection not controlled with antibiotics, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia that cannot be rate controlled with medications, or psychiatric illness/social situations that would limit compliance with study requirements Pregnant women are excluded from this study; breastfeeding should be discontinued if the mother is treated with these agents

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm I (tailored prednisone dose)<br>Participants receive rituximab IV, vincristine sulfate IV, doxorubicin hydrochloride IV, and cyclophosphamide IV on day 1. Participants also receive tailored prednisone dose PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: Cyclophosphamide<br>* Given IV<br>* Other names: WR- 138719;Drug: Doxorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubex;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Prednisone<br>* Given PO<br>* Other names: SK-Prednisone;Other: Quality-of-Life Assessment<br>* Ancillary correlative<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Biological: Rituximab<br>* Given IV<br>* Other names: RTXM83;Drug: Vincristine Sulfate<br>* Given IV<br>* Other names: Vincristine, sulfate;|
| Active Comparator: Arm II (usual care prednisone dose)<br>Participants receive rituximab, vincristine sulfate doxorubicin hydrochloride, and cyclophosphamide as in Arm I. Participants also receive usual care prednisone dose PO QD on days 1-5. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. | Drug: Cyclophosphamide<br>* Given IV<br>* Other names: WR- 138719;Drug: Doxorubicin Hydrochloride<br>* Given IV<br>* Other names: Rubex;Other: Laboratory Biomarker Analysis<br>* Correlative studies<br>Drug: Prednisone<br>* Given PO<br>* Other names: SK-Prednisone;Other: Quality-of-Life Assessment<br>* Ancillary correlative<br>* Other names: Quality of Life Assessment;Other: Questionnaire Administration<br>* Ancillary studies<br>Biological: Rituximab<br>* Given IV<br>* Other names: RTXM83;Drug: Vincristine Sulfate<br>* Given IV<br>* Other names: Vincristine, sulfate;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of hyperglycemia of standard or tailored rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP) | Will use the Kaplan Meier method to estimate the cumulative incidence of hyperglycemia, and the log-rank test to compare hyperglycemia incidence by arm after 3 cycles of R-CHOP chemotherapy. | After course 3 (63 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative incidence of hyperglycemia of standard or tailored R-CHOP | Will use the Kaplan Meier method to estimate the cumulative incidence of hyperglycemia, and the log-rank test to compare hyperglycemia incidence by arm after 6 cycles and after 6 months of R-CHOP chemotherapy. | Baseline up to 6 months | 
| Response rates of standard or tailored R-CHOP as measured by Cheson's criteria | Will use a Fisher's exact test to compare response rates after 6 cycles of R-CHOP by arm. | After of course 6 (126 days) | 
| Rates of grade III or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) criteria from standard or tailored R-CHOP | Will compare the rates of the incidence of grade III and higher events by arm of R-CHOP for each cycle using Fisher's exact tests. | Up to 6 months | 
| Severity of prednisone related adverse events using the Patient Reported Outcome (PRO)-CTCAE | Will compare the scoring of PRO-CTCAE assessments by arm of R-CHOP using two group t-tests at each time point of interest. | Up to course 6 (126 days) | 
| Health related quality of life (HRQOL) scores | Evaluated using the Functional Assessment of Cancer Therapy (FACT)-Lymphoma, FACT Gynecologic Oncology Group-Neurotoxicity additional concerns and Patient-Reported Outcomes Measurement Information System 29. Will compare the HRQOL measures between arms receiving R-CHOP chemotherapy using two group t-tests at each time point of interest. | Up to 6 months |