Acalabrutinib + Obinutuzumab for Non-Hodgkin's Lymphoma
Recruiting in Palo Alto (17 mi)
JB
Overseen byJonathon B Cohen, MD, MS
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Emory University
Must not be taking: CYP3A4 inhibitors, Proton pump inhibitors
Disqualifiers: High-grade lymphoma, CNS disease, others
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?
This trial studies acalabrutinib and obinutuzumab in patients with certain types of untreated lymphoma. Acalabrutinib blocks enzymes needed by cancer cells, while obinutuzumab helps the immune system fight these cells. The goal is to see if this combination can effectively kill more cancer cells.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot take certain medications like strong CYP3A4 inhibitors/inducers, warfarin, or proton pump inhibitors. If you are on proton pump inhibitors, you may switch to H2-receptor antagonists or antacids to participate.
What data supports the effectiveness of the drug combination Acalabrutinib and Obinutuzumab for Non-Hodgkin's Lymphoma?
Is the combination of Acalabrutinib and Obinutuzumab safe for humans?
Acalabrutinib, used alone or with Obinutuzumab, has shown a favorable safety profile in patients with B-cell malignancies, though it may increase the risk of neutropenia (low white blood cell count) and leukopenia (reduced white blood cells). Obinutuzumab, when combined with chemotherapy, was generally safe, with common mild infusion-related reactions and some cases of neutropenia.678910
What makes the drug Acalabrutinib + Obinutuzumab unique for treating Non-Hodgkin's Lymphoma?
Acalabrutinib is a highly selective Bruton tyrosine kinase inhibitor, and when combined with Obinutuzumab, an anti-CD20 antibody, it offers a targeted approach that may provide durable responses with a favorable safety profile compared to other treatments. This combination is particularly noted for its effectiveness in chronic lymphocytic leukemia, suggesting potential benefits for Non-Hodgkin's Lymphoma as well.28111213
Research Team
JB
Jonathon B Cohen, MD, MS
Principal Investigator
Emory University
Eligibility Criteria
This trial is for adults with untreated follicular lymphoma or other indolent non-Hodgkin lymphomas. Participants must be willing to use contraception, have no active high-grade cancers, and not require certain medications that could interfere with the study drugs. They should not have major health issues like uncontrolled autoimmune diseases, significant infections within 14 days before starting the trial, or a history of severe allergic reactions to similar drugs.Inclusion Criteria
You have certain types of untreated slow-growing lymphomas.
Willing and able to participate in all required evaluations and procedures in this study protocol
Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
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Exclusion Criteria
You have had cancer that needed ongoing treatment, unless there are specific exceptions.
You have uncontrolled autoimmune hemolytic anemia (AIHA) or idiopathic thrombocytopenic purpura (ITP).
Major surgical procedure within 28 days of first dose of study drug
See 19 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Induction
Patients receive acalabrutinib orally twice daily and obinutuzumab intravenously. Treatments repeat every 28 days for up to 12 cycles.
48 weeks
Multiple visits per cycle for drug administration
Follow-up
After cycle 12, patients are monitored for safety and effectiveness. Patients in complete response may discontinue or continue acalabrutinib. Follow-up includes regular assessments.
1 year
Every 12 weeks for 1 year, then every 6 months
Long-term Follow-up
Patients are monitored every 6 months until disease progression or next anti-lymphoma treatment.
Treatment Details
Interventions
- Acalabrutinib (Bruton's Tyrosine Kinase (BTK) Inhibitor)
- Obinutuzumab (Monoclonal Antibodies)
Trial OverviewThe trial is testing acalabrutinib combined with obinutuzumab in patients who haven't been treated before for their lymphoma. Acalabrutinib targets enzymes needed by cancer cells to grow while obinutuzumab works by helping the immune system affect cancer cell growth and spread.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: Treatment (acalabrutinib, obinutuzumab)Experimental Treatment4 Interventions
INDUCTION PHASE: Patients receive acalabrutinib PO BID on days 1-28. Patients also receive obinutuzumab 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 PR or 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Emory University Hospital/Winship Cancer InstituteAtlanta, GA
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Who Is Running the Clinical Trial?
Emory University
Lead Sponsor
Trials
1735
Patients Recruited
2,605,000+
AstraZeneca
Industry Sponsor
Trials
4491
Patients Recruited
290,540,000+
National Cancer Institute (NCI)
Collaborator
Trials
14080
Patients Recruited
41,180,000+
Findings from Research
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study.Palomba, ML., Till, BG., Park, SI., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia.Hoy, SM.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma.Dhillon, S.[2018]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Obinutuzumab: first global approval.Cameron, F., McCormack, PL.[2021]
Obinutuzumab is an effective treatment for chronic lymphocytic leukemia (CLL) and rituximab-refractory follicular lymphoma (FL), showing promise in combination with both chemotherapy and novel targeted therapies.
Future treatment strategies are likely to focus on chemotherapy-free regimens using obinutuzumab, aiming to enhance efficacy and improve patient safety through innovative combinations with other therapeutic agents.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Combination therapy with the type II anti-CD20 antibody obinutuzumab.Klein, C., Bacac, M., Umana, P., et al.[2017]
Acalabrutinib maleate tablets (AT) show comparable pharmacokinetics to the original acalabrutinib capsules (AC), making them a viable alternative for patients, especially since AT can be taken with food or proton-pump inhibitors (PPIs) without affecting drug absorption.
The safety profile of acalabrutinib remains favorable, with most adverse events being mild and no new safety concerns identified, indicating that AT is a safe option for treating chronic lymphocytic leukemia and other related conditions.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors.Sharma, S., Pepin, X., Burri, H., et al.[2023]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000).Radford, J., Davies, A., Cartron, G., et al.[2022]
Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, showed improved safety outcomes compared to other targeted therapies for treatment-naïve chronic lymphocytic leukemia (CLL) patients, although it was associated with a higher risk of neutropenia and leukopenia in some cases.
The analysis indicated that acalabrutinib (with or without obinutuzumab) had similar efficacy in terms of progression-free survival compared to other treatments, suggesting it is a safe and effective option for CLL patients.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia.Davids, MS., Telford, C., Abhyankar, S., et al.[2021]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Exposure-response analysis of acalabrutinib and its active metabolite, ACP-5862, in patients with B-cell malignancies.Edlund, H., Buil-Bruna, N., Vishwanathan, K., et al.[2022]
In a phase II study involving 217 patients with relapsed/refractory follicular lymphoma, the combination of zanubrutinib and obinutuzumab (ZO) showed a significantly higher overall response rate (ORR) of 69% compared to 46% for obinutuzumab alone, indicating greater efficacy.
The safety profile of ZO was manageable, with common side effects including thrombocytopenia and neutropenia, and serious adverse events like atrial fibrillation occurring in only 3% of patients, suggesting that ZO could be a promising treatment option for this patient population.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma.Zinzani, PL., Mayer, J., Flowers, CR., et al.[2023]
In a phase 3 study involving 535 patients with treatment-naive chronic lymphocytic leukaemia, acalabrutinib combined with obinutuzumab or as a monotherapy significantly improved progression-free survival compared to the standard treatment of obinutuzumab with chlorambucil, with median survival not reached for the acalabrutinib groups versus 22.6 months for the chlorambucil group.
The safety profile of acalabrutinib was favorable, with fewer infusion reactions and a lower incidence of grade 3 or higher adverse events compared to the obinutuzumab-chlorambucil group, indicating it is a viable chemotherapy-free treatment option for patients.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial.Sharman, JP., Egyed, M., Jurczak, W., et al.[2021]
In a phase 2 trial involving 124 patients with relapsed or refractory mantle cell lymphoma, acalabrutinib was associated with common treatment-related adverse events (AEs) like headache and diarrhea, but these did not lead to any treatment discontinuations.
Effective management strategies, including patient education and the use of over-the-counter medications for mild AEs, helped maintain treatment adherence and allowed for better tracking and management of nonadherence issues.
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma.Badillo, M., Nava, D., Rosa, M., et al.[2022]
NCBI (Pubmed)
pubmed.ncbi.nlm.nih.gov
Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia.Woyach, JA., Blachly, JS., Rogers, KA., et al.[2022]
References
Combination of Atezolizumab and Obinutuzumab in Patients with Relapsed/Refractory Follicular Lymphoma and Diffuse Large B-Cell Lymphoma: Results from a Phase 1b Study. [2022]
Obinutuzumab: a review of its use in patients with chronic lymphocytic leukaemia. [2018]
Obinutuzumab: A Review in Rituximab-Refractory or -Relapsed Follicular Lymphoma. [2018]
Obinutuzumab: first global approval. [2021]
Combination therapy with the type II anti-CD20 antibody obinutuzumab. [2017]
Bioequivalence and Relative Bioavailability Studies to Assess a New Acalabrutinib Formulation That Enables Coadministration With Proton-Pump Inhibitors. [2023]
Obinutuzumab (GA101) plus CHOP or FC in relapsed/refractory follicular lymphoma: results of the GAUDI study (BO21000). [2022]
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naïve chronic lymphocytic leukemia. [2021]
Exposure-response analysis of acalabrutinib and its active metabolite, ACP-5862, in patients with B-cell malignancies. [2022]
ROSEWOOD: A Phase II Randomized Study of Zanubrutinib Plus Obinutuzumab Versus Obinutuzumab Monotherapy in Patients With Relapsed or Refractory Follicular Lymphoma. [2023]
Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial. [2021]
Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]
Acalabrutinib plus Obinutuzumab in Treatment-Naïve and Relapsed/Refractory Chronic Lymphocytic Leukemia. [2022]