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

B-Cell Non-Hodgkin Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03505762
• Other study ID #: IRB00050108
• Secondary ID: NCI-2018-00585CC
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: July 19, 2018
• Est. completion date: October 2024

Study information

• Verified date: April 2024
• Source: Wake Forest University Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 80
• Est. completion date: October 2024
• Est. primary completion date: March 28, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• B-Cell Non-Hodgkin Lymphoma
• Hyperglycemia
• Lymphoma
• Lymphoma, B-Cell
• Lymphoma, Non-Hodgkin

Intervention

Drug:
• Cyclophosphamide
Given IV
• Doxorubicin Hydrochloride
Given IV

Other:
• Laboratory Biomarker Analysis
Correlative studies

Drug:
• Prednisone
Given PO

Other:
• Quality-of-Life Assessment
Ancillary correlative
• Questionnaire Administration
Ancillary studies

Biological:
• Rituximab
Given IV

Drug:
• Vincristine Sulfate
Given IV

Locations

Country	Name	City	State
United States	Wake Forest University Health Sciences	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Wake Forest University Health Sciences	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fasting blood glucose (FBG) levels	Will examine glucose variability over time in FBG using linear mixed effects models to model between and with-person variation in glucose.	Up to 6 months
Other	Hemoglobin A1C (HbA1c) levels	Will examine glucose variability over time in HbA1c using linear mixed effects models to model between and with-person variation in glucose.	Up to 6 months
Other	Fasting insulin	Will examine glucose variability over time in fasting insulin using linear mixed effects models to model between and with-person variation in glucose.	Up to 6 months
Other	Fructosamine levels	Will examine glucose variability over time in fructosamine using linear mixed effects models to model between and with-person variation in glucose.	Up to 6 months
Other	HRQOL scores in those with and without hyperglycemia	Will compare quality of life between the those who are hyperglycemic and those that are not at cycle 3, cycle 6, and 12 months using a mixed model analysis covariance (ANCOVA) with adjustment for baseline quality of life.	Up to 6 months
Other	Glycemic variability	To compare glycemic variability between the arms, will model variability using mixed effect models of FBG and random blood glucose over time, allowing for differing within-person variance by arm as well as fitting a model with pooled variance and any characteristics that differ between the groups. Will use likelihood ratio tests to compare if there is greater variability in the tailored versus standard arms by comparing the pooled variance model to the model that allows the within-person variation to vary by arm.	Up to 6 months
Other	Percentage of patients in the standard and tailored prednisone R-CHOP arms who complete all six cycles of chemotherapy	Will compare the proportion of participants by arm using Fisher's exact test.	End of course 6 (126 days)
Primary	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	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
Secondary	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)
Secondary	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
Secondary	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)
Secondary	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