An Open-Label Phase 2 Trial of Acalabrutinib Plus Obinutuzumab in Patients With Untreated, Low Tumor Burden Follicular Lymphoma and Other Indolent Non-Hodgkin Lymphomas
Summary
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.
Detailed description
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.
Arms & interventions
- DrugAcalabrutinib
Given PO
- BiologicalObinutuzumab
Given IV
- OtherQuality-of-Life Assessment
Ancillary studies
- OtherQuestionnaire Administration
Ancillary studies
Outcome measures
Primary
Complete 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
Secondary
Overall response rate
Time frame: Up to 3 years
CR rate for acalabrutinib monotherapy at end of single-agent run-in
Time frame: Up to 3 years
2-year progression free survival (PFS)
Time frame: From first dose to documented disease progression, or death from any cause, whichever occurs first, assessed at 2 years
Overall survival (OS)
Time frame: From first dose to death from any cause, assessed up to 3 years
Duration of response (DOR)
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 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
Time frame: Up to 3 years
Patient-reported adverse events.
Time frame: Up to 3 years
Eligibility criteria
Study locations (1)
Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia, 30322