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

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 for 30 days, then up to 6
months.

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