Acalabrutinib Plus Rituximab for the Treatment of Elderly or Low- to Intermediate-Risk Younger Untreated Mantle Cell Lymphoma

Acalabrutinib Plus Rituximab for the Treatment of Elderly or Low- to Intermediate-Risk Younger Untreated Mantle Cell Lymphoma: A Single-Arm, Open-Label, Multicenter, Phase II Study

This is a single- arm, open-label, multicenter, phase II study to evaluate Acalabrutinib plus Rituximab for the treatment of elderly or low- to intermediate-risk younger untreated mantle cell lymphoma

Study Overview

• Status: Recruiting
• Conditions: Mantle Cell Lymphoma (MCL)
• Intervention / Treatment: Drug: Acalabrutinib; Drug: Rituximab

Detailed Description

The purpose of this study is to evaluate the efficacy and safety of Acalabrutinib plus Rituximab for the treatment of elderly or low- to intermediate-risk younger untreated mantle cell lymphoma

Treatrment:

1. Acalabrutinib: 100 mg bid po, continue treatment until disease progression, intolerable toxicity, or completion of 24 months of treatment
2. Rituximab: 375 mg/m2 IV, once weekly during the first cycle, then once monthly for 12 months, followed by once every 2 months, for a maximum of 24 months.

The primary study endpoint is the investigator-assessed complete response (CR) rate at 12 months.

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Qingqing Cai; Phone Number: 02087342823; Email: caiqq@sysucc.org.cn

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 51000
      • Recruiting
      • Sun Yat-sen University Cancer Center, Sun Yat-sen University
      • Contact: Qingqing Cai; Phone Number: 02087342823; Email: caiqq@sysucc.org.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Key inclusion Criteria:

1. Age ≥18 years.
2. Histologically confirmed CD20+ mantle cell lymphoma.
3. No prior anti-lymphoma treatment.
4. Ann Arbor stage II-IV.
5. ECOG performance status 0-2, no deterioration >2 weeks before baseline or first dose.

6. Younger subjects (<65) must meet:

   1. Low to intermediate risk sMIPI (0-5)
   2. Ki67 < 50%
   3. No TP53 mutation (NGS)
   4. Lesion diameter ≤5 cm
   5. Non-blastoid, polymorphic disease
7. At least one assessable lesion per Lugano 2014 criteria.
8. Adequate organ and bone marrow function during screening.
9. Female subjects must use contraception as per local regulations.
10. Male subjects must agree to avoid sperm donation during the study and for 12 months post-rituximab.
11. Willing to undergo all required assessments and procedures, including swallowing capsules/tablets.
12. Able to understand the study's purpose and risks, and provide signed informed consent with authorization for the use of personal health information.

Key exclusion Criteria:

1. Participants with tumor burden reduction prior to stem cell transplantation.
2. History of active lymphoma central nervous system (CNS) involvement, leptomeningeal disease, or spinal cord compression.
3. Any disease evidence deemed by the investigator to be detrimental to the patient's participation or likely to affect protocol adherence (e.g., severe or uncontrolled systemic disease, including uncontrolled hypertension or kidney transplant).
4. History of progressive multifocal leukoencephalopathy (PML) or current diagnosis of PML.
5. Received any investigational drug within 30 days (or 5 half-lives, whichever is shorter) prior to the first dose of the investigational drug.
6. Underwent major surgery within 30 days prior to the first dose of the investigational drug. Note: If the participant has undergone major surgery, they must be fully recovered from any toxicity and/or complications related to the surgery before the first dose.
7. A history of malignancy that could affect protocol adherence or interpretation of results, except for: a. Basal cell carcinoma, squamous cell carcinoma of the skin, cervical carcinoma in situ, or prostate carcinoma in situ treated curatively at any time before the study. b. Other cancers that were treated surgically and/or with radiation, with no disease for ≥3 years without further treatment.
8. Significant cardiovascular disease, such as symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6 months before screening, or any NYHA Class 3 or 4 heart disease during screening. Note:Participants with well-controlled, asymptomatic atrial fibrillation are allowed.
9. Refractory nausea and vomiting, difficulty swallowing formulations, or malabsorption syndrome; chronic gastrointestinal disease, gastric bypass, or weight-loss surgery (e.g., Roux-en-Y); partial or complete bowel obstruction, or previous major intestinal surgery that may interfere with the absorption, distribution, metabolism, or elimination of the investigational drug.
10. Received a live-virus vaccine within 28 days prior to the first dose of the investigational drug.
11. Known HIV infection.
12. Any active major infection (e.g., bacterial, viral, or fungal, including subjects with positive CMV DNA PCR).
13. Serologic evidence of active hepatitis B or C infection.
14. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of the investigational drug.
15. History of bleeding disorders (e.g., hemophilia, Von Willebrand disease).
16. Requires or is receiving anticoagulation therapy with warfarin or equivalent vitamin K antagonists.
17. Requires strong CYP3A inhibitors or inducers. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks before the first dose of the investigational drug is prohibited.
18. Pregnancy or breastfeeding.
19. Participation in another therapeutic clinical trial.
20. Requires proton pump inhibitor therapy (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
21. Currently has a life-threatening disease, medical condition, or organ system dysfunction that, in the investigator's judgment, may compromise the participant's safety or place the study at risk.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Acalabrutinib in combination with Rituximab; Eligible patients will receive: Acalbrutinib : 100 mg bid po, continue treatment until disease progression, intolerable toxicity, or completion of 24 months of treatment. Rituximab: 375 mg/m² IV, once weekly during the first cycle, then once monthly for 12 months, followed by once every 2 months, for a maximum of 24 months.	Drug: Acalabrutinib; 100 mg bid po, continue treatment until disease progression, intolerable toxicity, or completion of 24 months of treatment.; Drug: Rituximab; 375 mg/m² IV, once weekly during the first cycle, then once monthly for 12 months, followed by once every 2 months, for a maximum of 24 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response(CR)	Defined as the proportion of patients who achieve complete remission	From the start of treatment with the investigational drug until 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective response rate(ORR)	The proportion of patients who achieve complete remission (CR) or partial remission (PR) .	From the start of treatment with the investigational drug until 12 months
Duration of Response(DOR)	To investigate the preliminary anti-tumor efficacy	The time from the patient's first efficacy assessment achieving CR or PR until disease progression, up to 5 years
Progression-free survival(PFS)	To investigate the preliminary anti-tumor efficacy	From the date of enrollment until the date of the first documented progression or date of death from any cause, whichever came first, up to 5 years
Overall survival(OS)	To investigate the preliminary anti-tumor efficacy	From the date of enrollment until the date of death from ant cause, up to 5 years

Collaborators and Investigators

• Sponsor: Sun Yat-sen University

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2025
• Primary Completion (Estimated): February 10, 2033
• Study Completion (Estimated): February 20, 2033

Study Registration Dates

• First Submitted: February 16, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): February 26, 2025

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Lymphatic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Lymphoma, Non-Hodgkin; Lymphoma; Lymphoma, Mantle-Cell; Antineoplastic Agents, Immunological; Tyrosine Kinase Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Rituximab; Acalabrutinib
• Other Study ID Numbers: B2024-843

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No