Acalabrutinib and Rituximab for the Treatment of Previously Untreated Mantle Cell Lymphoma
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|ClinicalTrials.gov Identifier: NCT04765111|
Recruitment Status : Not yet recruiting
First Posted : February 21, 2021
Last Update Posted : February 26, 2021
|Condition or disease||Intervention/treatment||Phase|
|Mantle Cell Lymphoma||Drug: Acalabrutinib Biological: Rituximab||Phase 2|
I. To determine the efficacy measured by complete remission (CR) rate of the acalabrutinib in combination with rituximab in newly diagnosed elderly mantle cell lymphoma (MCL) patients.
II. To determine the safety profile of acalabrutinib with rituximab combination in elderly patients with MCL.
I. To evaluate the overall response (OR) rate. II. To evaluate the progression-free survival and overall survival. III. To assess serial minimal residual disease (MRD) using clonoseq, circulating tumor deoxyribonucleic acid (ct-DNA) based serial clonal evolution.
IV. Perform baseline genomic profiling for recognizing the predictive signature for response, serial MCL specific analytes assessments while on therapy.
I. Clonal evolution with targeted sequencing (seq) on ctDNA samples in sequential samples using a MCL specific customized gene panel would be assessed.
II. MRD assay using IgH clonoseq and ctDNA analysis, flow cytometry at various time points from peripheral blood (PB)/bone marrow (BM).
III. Sequential immunologic studies with cytokines/chemokines using a analyte panel, T cell numbers, and immunoglobulins (Ig).
IV. Tissue microenvironmental studies with simultaneous assessment of PB, BM and lymph nodes for gene expression profiling (GEP), single cell seq, ribonucleic acid (RNA) seq and clonal heterogeneity and the impact of acalabrutinib (A)-rituximab (R) treatment.
V. Extensive bioinformatics studies. VI. Identification of signaling pathways or biomarkers that predict sensitivity after therapy.
Patients receive acalabrutinib orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab intravenously (IV) over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 16, 18, 20, and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.
After completion of study intervention, patients are followed up at 30 days, every 4 months for 2 years, every 6 months for 2 years, and then annually for 3 years.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase II Study of Acalabrutinib Plus Rituximab in Previously Untreated Elderly Patients With Mantle Cell Lymphoma|
|Estimated Study Start Date :||June 30, 2021|
|Estimated Primary Completion Date :||August 22, 2022|
|Estimated Study Completion Date :||August 22, 2022|
Experimental: Treatment (acalabrutinib, rituximab)
Patients receive acalabrutinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive rituximab IV over 3-4 hours on days 1, 8, 15, and 22 of cycle 1, and day 1 of cycles 2-12, 14, 18, 20, 22, and 24. Cycles repeats every 28 days for up to 24 months or until complete remission is achieved in the absence of disease progression or unacceptable toxicity.
- Complete remission rate [ Time Frame: At 16 weeks ]
- Incidence of adverse events (AEs) [ Time Frame: Up to 30 days following the last dose of study drug ]Toxicity is defined as all related grade 3 or higher AEs and not only the non-hematologic AEs will be considered toxicities treatment-related grade 3 or higher AEs within the first three cycles, and any treatment-related toxicities, which cause drug delays for more than 4 weeks. Toxicity data by type and severity will be summarized by frequency tables for all patients by Common Terminology Criteria for Adverse Events version 5.0.
- Overall response rate [ Time Frame: Up to 7 years ]Summary statistics including mean, standard deviation, median, and range for continuous variables, frequency count and percentage categorical variables will be reported. Complete response rate and its posterior credibility interval will be calculated. Response rate and its 95% confidence interval will be estimated. Logistic regression model may be fitted to assess the effects of important patient prognostic factors on response.
- Progression free survival (PFS) [ Time Frame: From the start of the treatment to progression or death due to any cause whichever happened first, assessed up to 7 years ]Estimated using Kaplan and Meier method. The log-rank test will be used to evaluate the difference in PFS between patient groups.
- Overall survival (OS) [ Time Frame: From the start of the treatment to death due to any cause, assessed up to 7 years ]Estimated using Kaplan and Meier method. The log-rank test will be used to evaluate the difference in OS between patient groups.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04765111
|Contact: Luhua (Michael) Wangfirstname.lastname@example.org|
|United States, Texas|
|M D Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Contact: Luhua (Michael) Wang 713-792-2860|
|Principal Investigator: Luhua (Michael) Wang|
|Principal Investigator:||Luhua (Michael) Wang||M.D. Anderson Cancer Center|