Acalabrutinib + Obinutuzumab + Glofitamab for Mantle Cell Lymphoma
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: City of Hope Medical Center
No Placebo Group
Prior Safety Data
Breakthrough Therapy
Trial Summary
What is the purpose of this trial?This phase II trial studies the side effects of acalabrutinib, obinutuzumab, and glofitamab and how well they work together for treating patients with mantle cell lymphoma that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Acalabrutinib is in a class of medications called kinase inhibitors. It blocks a protein called BTK, which is present on B-cell (a type of white blood cells) cancers such as mantel cell lymphoma at abnormal levels. This may help keep cancer cells from growing and spreading. A monoclonal antibody is a type of protein that can bind to certain targets in the body, such as molecules that cause the body to make an immune response (antigens). Immunotherapy with monoclonal antibodies, such as obinutuzumab, may help the body's immune system attack the cancer, and may interfere with the ability of cancer cells to grow and spread. Glofitamab is a class of medications called bispecific antibodies. Bispecific antibodies are designed to simultaneously bind to T cells and cancer cell antigens, leading to T-cell activation, proliferation, and cancer cell death. Giving acalabrutinib, obinutuzumab, and glofitamab together may be a safe and effective treatment for patients with relapsed or refractory mantle cell lymphoma.
Is the drug Acalabrutinib, Glofitamab, Obinutuzumab a promising treatment for Mantle Cell Lymphoma?Yes, the drug Acalabrutinib, Glofitamab, Obinutuzumab is promising for Mantle Cell Lymphoma. Acalabrutinib has been approved by the FDA for this type of cancer and has shown good results in studies. It is known for being effective and having a favorable safety profile compared to other treatments.23568
What safety data is available for the treatment of Acalabrutinib, Obinutuzumab, and Glofitamab in Mantle Cell Lymphoma?Acalabrutinib, a selective Bruton tyrosine kinase inhibitor, has been approved for relapsed or refractory mantle cell lymphoma and shows a tolerable safety profile with most adverse events being mild (grade 1/2), such as headaches and diarrhea. Serious adverse reactions are rare, and it has improved tolerability over ibrutinib. Acalabrutinib combined with obinutuzumab has shown improved safety outcomes compared to other therapies, though there is an increased risk of neutropenia and leukopenia. Obinutuzumab, when used with acalabrutinib, has been part of studies showing favorable safety profiles. Glofitamab, marketed as COLUMVI, is not specifically mentioned in the provided abstracts, so its safety data in combination with acalabrutinib and obinutuzumab is not detailed here.23567
What data supports the idea that Acalabrutinib + Obinutuzumab + Glofitamab for Mantle Cell Lymphoma is an effective drug?The available research shows that Acalabrutinib, a key component of the treatment, has been approved for use in mantle cell lymphoma after showing positive results in studies. It is noted for its safety and effectiveness, especially for patients who have already tried other treatments. Compared to other drugs, Acalabrutinib has a favorable safety profile, meaning it causes fewer side effects, which is important for patients who need long-term treatment. While specific data on the combination with Obinutuzumab and Glofitamab for mantle cell lymphoma isn't detailed, Acalabrutinib's approval and its use in similar conditions suggest it is a promising option.12346
Do I need to stop my current medications to join the trial?The trial protocol does not specify if you need to stop taking your current medications. However, you cannot participate if you require treatment with a strong CYP3A4 inhibitor/inducer or if you have had certain treatments like therapeutic anti-cancer antibodies within 4 weeks, or systemic immunosuppressive medications within 2 weeks before starting the trial. Systemic steroid therapy must be tapered down to 20 mg/day prednisone or equivalent, with some exceptions. It's best to discuss your current medications with the study team.
Eligibility Criteria
This trial is for adults with mantle cell lymphoma that has returned or didn't respond to previous treatments. Participants must be in fairly good health, have a certain level of blood counts and organ function, and agree to use effective birth control. People can't join if they've had certain recent cancer treatments, used T-cell engaging bispecific antibodies before, or been exposed to BTK inhibitors like ibrutinib.Inclusion Criteria
I am 18 years old or older.
My lymphoma is confirmed as mantle cell type.
My white blood cell count is healthy, or I have bone marrow involvement.
My kidney function, measured by creatinine levels or clearance, is normal.
My tumor is CD20 positive after my latest treatment.
My platelet count is above 75,000/mm^3 without bone marrow involvement or above 30,000/mm^3 with it.
My condition worsened or didn't improve after at least one treatment.
I have recovered from side effects of cancer treatment, except for hair loss.
I am a woman who can have children and my pregnancy test is negative.
My blood clotting measurements are within safe limits.
I am able to get out of my bed or chair and move around.
My hemoglobin level is at least 8 g/dL, unless it's low because of my illness.
Exclusion Criteria
I have previously been treated with a BTK inhibitor.
I have been treated with a bispecific antibody before.
Participant Groups
The trial tests the combination of acalabrutinib (a kinase inhibitor), obinutuzumab (a monoclonal antibody), and glofitamab (a bispecific antibody) on patients with relapsed/refractory mantle cell lymphoma. It aims to see how well these drugs work together and what side effects they might cause.
1Treatment groups
Experimental Treatment
Group I: Treatment (acalabrutinib, obinutuzumab, glofitamab)Experimental Treatment9 Interventions
Patients recieve acalabrutinib PO BID of each cycle, obinutuzumab IV on days 1 and 7 of cycle 1 only, and glofitamab IV over 2-4 hours on days 8 and 15 of cycle 1 and day 1 of each subsequent cycle. Treatment repeats every 21 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients with MRD positive CR, PR, or SD after 12 cycles of protocol therapy may continue receiving single agent acalabrutinib per standard of care during the follow-up phase of the study. Patients also undergo a ECHO or MUGA during screening, as well as PET/CT or CT, and blood specimen collection throughout the trial. Patients may also undergo bone marrow biopsies throughout the trial.
Acalabrutinib is already approved in United States, European Union for the following indications:
๐บ๐ธ Approved in United States as Calquence for:
- Mantle cell lymphoma
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
๐ช๐บ Approved in European Union as Calquence for:
- Chronic lymphocytic leukemia
- Small lymphocytic lymphoma
- Mantle cell lymphoma
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
City of Hope Medical CenterDuarte, CA
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Who is running the clinical trial?
City of Hope Medical CenterLead Sponsor
National Cancer Institute (NCI)Collaborator
References
Ofatumumab Exhibits Enhanced In Vitro and In Vivo Activity Compared to Rituximab in Preclinical Models of Mantle Cell Lymphoma. [2019]Mantle cell lymphoma (MCL) is a mature B-cell lymphoma considered to be incurable with current treatments, including first-line rituximab in combination with multiagent chemotherapy and for those eligible, high-dose chemotherapy and stem cell support or rituximab maintenance. On the other hand, achieving a complete remission by high-sensitive flow cytometry is associated with prolonged duration of remission, stressing the need to develop and/or incorporate novel agents into the management of MCL. To this end, we examined the activity of ofatumumab, an anti-CD20 monoclonal antibody with distinct binding and immunologic properties compared to rituximab, in MCL preclinical models.
Acalabrutinib: First Global Approval. [2018]Acerta Pharma is developing the Bruton's tyrosine kinase inhibitor acalabrutinib (Calquence®) for the treatment of various haematological and solid malignancies. The drug has received accelerated approval from the US FDA for the treatment of mantle cell lymphoma based on the results of a phase II study, and phase III trials in mantle cell lymphoma and chronic lymphocytic leukaemia are currently underway. This article summarizes the milestones in the development of acalabrutinib leading to this first approval for mantle cell lymphoma.
Use of acalabrutinib in patients with mantle cell lymphoma. [2021]Acalabrutinib, a selective Bruton tyrosine kinase (BTK) inhibitor, was granted accelerated approval by the FDA on 31 October 2017 for the treatment of patients with mantle cell lymphoma (MCL) who have received at least one prior therapy. Areas covered: This narrative review provides an overview of acalabrutinib, its use in clinical practice and potential future developments. Expert commentary: BTK inhibitors have demonstrated efficacy in patients with relapsed or refractory MCL. To prepare patients for therapy, all preexisting infections should be diagnosed and treated, and infection prophylaxis undertaken. Serious adverse reactions are rare with acalabrutinib; however, patients should be made aware of common adverse events such as headaches, which usually resolve within one month without medical treatment. Interaction with other drugs appears to be less of an issue with acalabrutinib than with ibrutinib; however, patients receiving acalabrutinib therapy must be advised not to take any additional medications without first consulting with their treating physician. A key unmet medical need is treatment options for patients in whom BTK inhibitors are discontinued, because of either intolerance or refractory disease. Patients not tolerating ibrutinib could be switched to acalabrutinib, which has improved selectivity and increased tolerability. First-line treatment with acalabrutinib is being investigated.
Matching-adjusted Indirect Comparisons of the Efficacy and Safety of Acalabrutinib Versus Other Targeted Therapies in Relapsed/Refractory Mantle Cell Lymphoma. [2021]Mantle cell lymphoma (MCL) is a rare subtype of B-cell non-Hodgkin lymphoma that can be either aggressive or indolent. Although MCL usually responds well to initial treatment with chemotherapy-based regimens, the disease often relapses or becomes refractory within a few years. Acalabrutinib is a highly selective, potent, covalent Bruton tyrosine kinase inhibitor with minimal off-target activity. WIthout head-to-head clinical trial data, estimation of the comparative efficacy and safety of new therapeutic entities provides valuable information for patients, clinicians, and health care payers. The objective of this analysis was to compare the efficacy and safety of acalabrutinib versus other targeted therapies employed for the treatment of relapsed/refractory MCL by using matching-adjusted indirect comparisons.
Acalabrutinib: Managing Adverse Events and Improving Adherence in Patients With Mantle Cell Lymphoma. [2022]Acalabrutinib is a selective Bruton tyrosine kinase inhibitor approved for patients with relapsed or refractory mantle cell lymphoma, an aggressive B-cell malignancy. Treatment-related adverse events (AEs) can have a negative effect on treatment adherence.
Matching-adjusted indirect comparisons of safety and efficacy of acalabrutinib versus other targeted therapies in patients with treatment-naรฏve chronic lymphocytic leukemia. [2021]Acalabrutinib is a highly selective, potent, next-generation, covalent Bruton tyrosine kinase inhibitor with minimal off-target activity. Matching-adjusted indirect comparisons (MAICs) were performed to estimate the safety and efficacy of acalabrutinib compared to other targeted therapies for treatment-naïve patients with chronic lymphocytic leukemia (CLL). Individual patient data for acalabrutinib (ELEVATE-TN trial) were matched to aggregate baseline characteristics for comparators. After matching, acalabrutinib (with or without obinutuzumab) showed improved safety outcomes, except for increased risk of neutropenia (p < 0.001) for acalabrutinib plus obinutuzumab versus ibrutinib and increased risk of leukopenia (p < 0.05) for acalabrutinib (with or without obinutuzumab) versus venetoclax plus obinutuzumab. There was no statistically significant difference in progression-free survival between acalabrutinib (with or without obinutuzumab) and any of the comparators. This MAIC demonstrated a favorable safety profile for acalabrutinib-based therapy compared with other targeted therapies in treatment-naïve patients with CLL, without compromising efficacy.
Acalabrutinib: A Selective Bruton Tyrosine Kinase Inhibitor for the Treatment of B-Cell Malignancies. [2023]Bruton tyrosine kinase (BTK) is a validated target for treatment of B-cell malignancies, and oral inhibitors of BTK have emerged as a standard of care for these diseases. Acalabrutinib is a second generation, highly selective, potent, covalent BTK inhibitor that exhibits minimal off-target activity in in vitro assays, providing the potential to improve tolerability over the first-in-class BTK inhibitor, ibrutinib. Acalabrutinib was approved for the treatment of relapsed/refractory mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) in the US in 2017 and 2019, respectively. Acalabrutinib is also undergoing trials for other B-cell malignancies, both as monotherapy and in combinations. In this review, we discuss results from clinical trials evaluating the efficacy and safety of acalabrutinib in patients with CLL, MCL, and Waldenstrom's macroglobulinemia. Recent phase 3 data showed that acalabrutinib improved progression-free survival (PFS) compared with rituximab plus idelalisib or rituximab plus bendamustine in patients with relapsed/refractory CLL, and acalabrutinib with or without obinutuzumab improved PFS compared with chlorambucil plus obinutuzumab in patients with treatment-naïve CLL. Overall, acalabrutinib had a tolerable safety profile, with most adverse events being grade 1/2 severity (most commonly headache and diarrhea) and a low rate of discontinuation due to adverse events.
Acalabrutinib Versus Investigator's Choice in Relapsed/Refractory Chronic Lymphocytic Leukemia: Final ASCEND Trial Results. [2022]Acalabrutinib is a Bruton tyrosine kinase inhibitor approved for patients with chronic lymphocytic leukemia (CLL). ASCEND is the pivotal phase 3 study of acalabrutinib versus investigator's choice of idelalisib plus rituximab (IdR) or bendamustine plus rituximab (BR) in patients with relapsed/refractory (R/R) CLL. In the primary ASCEND analysis (median 16.1-month follow-up), acalabrutinib showed superior efficacy with an acceptable tolerability profile versus IdR/BR; here, we report final ~4 year follow-up results. Patients with R/R CLL received oral acalabrutinib 100 mg twice daily until progression or unacceptable toxicity, or investigator's choice of IdR or BR. A total of 310 patients (acalabrutinib, n = 155; IdR, n = 119; BR, n = 36) were enrolled. At median follow-up of 46.5 months (acalabrutinib) and 45.3 months (IdR/BR), acalabrutinib significantly prolonged investigator-assessed progression-free survival (PFS) versus IdR/BR (median, not reached [NR] vs 16.8 months; P < 0.001); 42-month PFS rates were 62% (acalabrutinib) versus 19% (IdR/BR). Median overall survival (OS) was NR (both arms); 42-month OS rates were 78% (acalabrutinib) versus 65% (IdR/BR). Adverse events led to drug discontinuation in 23%, 67%, and 17% of patients in the acalabrutinib, IdR, and BR arms, respectively. Events of clinical interest (acalabrutinib vs IdR/BR) included all-grade atrial fibrillation/flutter (8% vs 3%), all-grade hypertension (8% vs 5%), all-grade major hemorrhage (3% vs 3%), grade ≥3 infections (29% vs 29%), and second primary malignancies excluding nonmelanoma skin cancer (7% vs 2%). At ~4 years follow-up, acalabrutinib maintained favorable efficacy versus standard-of-care regimens and a consistent tolerability profile in patients with R/R CLL.