Acalabrutinib with rituximab for untreated mantle cell lymphoma in older adults and lower-risk younger patients

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 trial tests whether combining acalabrutinib and rituximab can produce complete remissions at 12 months in people with untreated mantle cell lymphoma who are elderly or younger with low- to intermediate-risk disease.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Sun Yat-sen University (Academic / other)
• Drugs / interventions: rituximab, radiation, Acalabrutinib
• Locations: 1 site (Guangzhou, Guangdong)
• Trial ID: NCT06846489 on ClinicalTrials.gov

What this trial studies

This is a single-arm, open-label phase II study giving acalabrutinib 100 mg twice daily together with scheduled rituximab infusions to adults with untreated mantle cell lymphoma who are either elderly or younger but low- to intermediate-risk. Rituximab is given weekly in the first cycle, then monthly for 12 months and every two months thereafter, while acalabrutinib is continued up to 24 months or until disease progression or intolerable toxicity. The primary endpoint is investigator-assessed complete response rate at 12 months, and safety/tolerability are monitored throughout. The study is conducted at Sun Yat-sen University Cancer Center in Guangzhou, China.

Who should consider this trial

Good fit: Ideal candidates are adults with previously untreated, CD20-positive mantle cell lymphoma who are elderly or younger (<65) with low- to intermediate-risk sMIPI, Ki-67 <50%, no TP53 mutation, lesion diameter ≤5 cm, non-blastoid histology, ECOG 0–2, and adequate organ function.

Not a fit: Patients with high-risk features such as TP53 mutation, Ki-67 ≥50%, blastoid morphology, large lesions >5 cm, prior lymphoma treatment, or those needing intensive chemo are unlikely to benefit from this regimen.

Why it matters

Potential benefit: If successful, this chemo-free combination could offer older or lower-risk younger patients a tolerable option that achieves high complete remission rates without conventional cytotoxic chemotherapy.

How similar studies have performed: BTK inhibitors like ibrutinib and acalabrutinib, often combined with anti-CD20 antibodies, have shown promising response rates in mantle cell lymphoma, but this specific combination in a selected low- to intermediate-risk untreated population is being tested prospectively.

Eligibility criteria

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.

Where this trial is running

Guangzhou, Guangdong

• Sun yat-sen university cancer center, Sun yat-sen university — Guangzhou, Guangdong, China (Recruiting)

Study contacts

• Study coordinator: Qingqing Cai

Conditions Mantle Cell Lymphoma