B-Cell Non-Hodgkin Lymphoma
Conditions
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 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. V. To compare overall survival (OS) between standard or tailored R-CHOP 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.
Interventions
DRUGCyclophosphamide
Given IV
DRUGDoxorubicin Hydrochloride
Given IV
OTHERLaboratory Biomarker Analysis
Correlative studies
DRUGPrednisone
Given PO
OTHERQuality-of-Life Assessment
Ancillary correlative
OTHERQuestionnaire Administration
Ancillary studies
BIOLOGICALRituximab
Given IV
DRUGVincristine Sulfate
Given IV
Sponsors
Wake Forest University Health Sciences
National Cancer Institute (NCI)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of B cell non-Hodgkin lymphoma confirmed by World Health Organization (WHO) criteria * Planned treatment with R-CHOP chemotherapy * 18 years of age or older * Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 3 * Life expectancy of greater than 3 months with chemotherapy * The effects of R-CHOP on the developing human fetus are unknown. For this reason, 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
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 because R-CHOP includes D Class agents with the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with R-CHOP, breastfeeding should be discontinued if the mother is treated with these agents
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Percentage of Patients With Hyperglycemia Patients of Standard or Tailored Rituximab, Cyclophosphamide, Doxorubicin Hydrochloride, Vincristine Sulfate and Prednisone (R-CHOP) | After course 3 (63 days) | Will use the Kaplan Meier method to estimate the cumulative percentage of patients with hyperglycemia, and the log-rank test to compare hyperglycemia rates by arm after 3 cycles of R-CHOP chemotherapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Incidence of Hyperglycemia of Standard or Tailored R-CHOP | from baseline through 6 cycles (126 days) and at 6 months after completion of chemotherapy | 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 (up to 400 days from start of treatment) of R-CHOP chemotherapy. |
| Response Rates of Standard or Tailored R-CHOP as Measured by Cheson's Criteria | After course 6 (126 days) | Will use a Fisher's exact test to compare response rates (complete response) through 6 cycles of R-CHOP by arm. Response is determined by Cheson's criteria. |
| Rates of Grade III or Higher Adverse Events Using Common Terminology Criteria for Adverse Events (CTCAE) Criteria From Standard or Tailored R-CHOP | Up to 6 months (up to 400 days from start of treatment) | Will compare the rates of the incidence of grade III and higher adverse events using Common Terminology Criteria for Adverse Events (CTCAE) criteria by arm of R-CHOP for each cycle using Fisher's exact tests. |
| Severity of Prednisone Related Adverse Events Using the Patient Reported Outcome (PRO)-CTCAE | Up to course 6 (126 days) | Compare the worst severity of PRO-CTCAE assessments by arm of R-CHOP using two group t-tests. The questionnaire was completed at each cycle (1-6) and the worst response for each participant for each measure was calculated for comparison. Severity for each measure was captured on a 5 point scale with 1=None and 5=Very severe. |
| Health Related Quality of Life (HRQOL) Scores | Day 1 of cycles 1, 4, 6, and 6 months post treatment (up to 400 days from start of treatment) | Evaluated using the Functional Assessment of Cancer Therapy (FACT)-Lymphoma, FACT Gynecologic Oncology Group (GOG)-Neurotoxicity (nxt) 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 (day 1 of cycles 1, and 4, after cycle 6, and 6 months post treatment (up to 400 days from start of treatment)). Measures reported are the total FACT-lymphoma score ranging from 0-168 and the FACT-GOG neurotoxicity subscale ranging from 0-16. For both measures higher values indicate of better health related quality of life. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRakhee Vaidya, MD
Wake Forest University Health Sciences
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 42 Participants |
| Age, Categorical Between 18 and 65 years | 38 Participants |
| Age, Continuous | 65 years |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 72 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 21 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 7 / 39 | 9 / 39 |
| other Total, other adverse events | 39 / 39 | 39 / 39 |
| serious Total, serious adverse events | 10 / 39 | 11 / 39 |
Outcome results
None listed