Clinical trial NCT03505762: Tailored Prednisone Reduction in Preventing Hyperglycemia in Participants With B-Cell Non-Hodgkin Lymphoma Receiving Combination Chemotherapy Treatment
Official title: A Randomized Phase II Pilot of Tailored Prednisone Reduction Versus Usual Care for the Treatment of Hyperglycemia During R-CHOP Chemotherapy
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: B-Cell Non-Hodgkin Lymphoma
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2018-04-23
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cumulative incidence of hyperglycemia of standard or tailored rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine sulfate and prednisone (R-CHOP)
timeFrame: After course 3 (63 days)
Secondary outcomes:
measure: Cumulative incidence of hyperglycemia of standard or tailored R-CHOP
timeFrame: Baseline up to 6 months
measure: Response rates of standard or tailored R-CHOP as measured by Cheson's criteria
timeFrame: After of course 6 (126 days)
measure: Rates of grade III or higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) criteria from standard or tailored R-CHOP
timeFrame: Up to 6 months
measure: Severity of prednisone related adverse events using the Patient Reported Outcome (PRO)-CTCAE
timeFrame: Up to course 6 (126 days)
measure: Health related quality of life (HRQOL) scores
timeFrame: Up to 6 months
Other outcomes:
measure: Fasting blood glucose (FBG) levels
timeFrame: Up to 6 months
measure: Hemoglobin A1C (HbA1c) levels
timeFrame: Up to 6 months
measure: Fasting insulin
timeFrame: Up to 6 months
measure: Fructosamine levels
timeFrame: Up to 6 months
measure: HRQOL scores in those with and without hyperglycemia
timeFrame: Up to 6 months
measure: Glycemic variability
timeFrame: Up to 6 months
measure: Percentage of patients in the standard and tailored prednisone R-CHOP arms who complete all six cycles of chemotherapy
timeFrame: End of course 6 (126 days)
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest University Health Sciences
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Rakhee Vaidya
role: PRINCIPAL_INVESTIGATOR
References: