This phase II trial studies the effect of acalabrutinib and obinutuzumab in treating patients with follicular lymphoma or other indolent non-Hodgkin lymphoma for which the patient has not received treatment in the past (previously untreated). Acalabrutinib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Immunotherapy with obinutuzumab may induce changes in body's immune system and may interfere with the ability of cancer cells to grow and spread. Giving acalabrutinib and obinutuzumab may kill more cancer cells.
PRIMARY OBJECTIVE: I. To determine if treatment acalabrutinib and obinutuzumab is effective in patients with untreated, low tumor burden follicular lymphoma and other indolent non-Hodgkin lymphomas (NHLs). SECONDARY OBJECTIVES: I. Determine the complete response (CR) rate for single agent acalabrutinib at the end of a single-agent run-in for patients with untreated low tumor burden follicular lymphoma (FL). II. Determine tolerability of acalabrutinib and obinutuzumab via assessment of patient-reported outcomes and conventional assessments. III. Assess duration of response and long-term outcomes including progression-free survival. IV. Assess the impact of early treatment with this regimen on health-related quality of life. TERTIARY/EXPLORATORY OBJECTIVES: I. Evaluate the impact of treatment discontinuation in patients who have achieved a complete response at the end of the induction phase. II. To assess the safety and efficacy of acalabrutinib and obinutuzumab in other subtypes of indolent NHL. OUTLINE: INDUCTION PHASE: Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Patients also receive obinutuzumab intravenously (IV) on days 1, 8, and 15 of cycle 3, then on day 1 of cycles 4-8. Treatments repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. FOLLOW-UP PHASE: After cycle 12, patients who are in CR are randomized to either discontinue acalabrutinib or to continue acalabrutinib monotherapy in the absence of disease progression or unacceptable toxicity. Patients with partial response (PR) or stable disease (SD) after cycle 12 continue acalabrutinib monotherapy in the absence of disease progression or unacceptable toxicity. Patients with disease progression after cycle 12 discontinue study treatment. Patients with disease progression at any time prior to the conclusion of cycle 12 may continue study therapy if they are felt to be benefiting by the treating physician, but not past cycle 12. After completion of study treatment, patients are followed up at 30 days, every 12 weeks for 1 year, then every 6 months until disease progression or next anti-lymphoma treatment.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, United States
RECRUITINGComplete response (CR) rate
Complete response rate will be calculated, and a 95% confidence interval will be estimated using the Clopper-Pearson method.
Time frame: Up to start of cycle 6 (each cycle = 28 days)
Incidence of grade 3+ adverse events
Assessed by Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Time frame: Up to 30 days post treatment
Overall response rate
Overall response rate will be calculated, and a 95% confidence interval will be estimated using the Clopper-Pearson method.
Time frame: Up to 3 years
CR rate for acalabrutinib monotherapy at end of single-agent run-in
Will be calculated, and a 95% confidence interval will be estimated using the Clopper-Pearson method.
Time frame: Up to 3 years
2-year progression free survival (PFS)
PFS will be estimated using Kaplan-Meier methodology. Approximate 95% confidence intervals (CIs) for median PFS will be computed using the Brookmeyer and Crowley method.
Time frame: From first dose to documented disease progression, or death from any cause, whichever occurs first, assessed at 2 years
Overall survival (OS)
Duration of OS will be estimated using Kaplan-Meier methodology. Approximate 95% CIs for median OS will computed using the Brookmeyer and Crowley method.
Time frame: From first dose to death from any cause, assessed up to 3 years
Duration of response (DOR)
DOR will be estimated using Kaplan-Meier method. Approximate 95% CIs for median DOR will be computed using the Brookmeyer and Crowley method.
Time frame: From the first tumor assessment supports the response to the time of confirmed disease progression or death due to any cause, whichever occurs first, assessed up to 3 years
Time to next anti-lymphoma treatment
Time to next anti-lymphoma treatment is defined as the time from the end of induction visit up to and including the date of initiation of next treatment for any reason. This includes any chemotherapy, antibody therapy, oral therapy, and radiation therapy. Time to next anti-lymphoma treatment will be estimated using Kaplan-Meier methodology. Approximate 95% CIs for median time to next anti-lymphoma treatment will be computed using the Brookmeyer and Crowley method
Time frame: From the end of induction visit up to and including the date of initiation of next treatment for any reason, assessed up to 3 years
Quality of life (QOL) assessments
QOL measures from the Functional Assessment of Cancer Therapy General questionnaire obtained during treatment will be compared to the baseline values obtained at the screening visit using paired t-tests, McNemar's tests, or their nonparametric equivalents, where appropriate.
Time frame: Up to 3 years
Patient-reported adverse events.
Categorical Patient Reported Outcomes (PRO)-CTCAE variables will be summarized using frequencies and percentages, and numeric PRO-CTCAE variables will be summarized using mean, median, standard deviation, interquartile range (IQR), and range.
Time frame: Up to 3 years
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