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

Official title

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

Overview

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

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.

Interventions

• 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

Primary outcome measures

• Complete Response(CR) [Time frame: From the start of treatment with the investigational drug until 12 months]

Secondary outcome measures (4)

• Objective response rate(ORR) [Time frame: From the start of treatment with the investigational drug until 12 months]
• Duration of Response(DOR) [Time frame: The time from the patient's first efficacy assessment achieving CR or PR until disease progression, up to 5 years]
• Progression-free survival(PFS) [Time frame: 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) [Time frame: From the date of enrollment until the date of death from ant cause, up to 5 years]

Eligibility criteria

Inclusion criteria

• Age ≥18 years.
• Histologically confirmed CD20+ mantle cell lymphoma.
• No prior anti-lymphoma treatment.
• Ann Arbor stage II-IV.
• ECOG performance status 0-2, no deterioration >2 weeks before baseline or first dose.
• Younger subjects (<65) must meet:

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

Exclusion criteria

• Participants with tumor burden reduction prior to stem cell transplantation.
• History of active lymphoma central nervous system (CNS) involvement, leptomeningeal disease, or spinal cord compression.
• 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).
• History of progressive multifocal leukoencephalopathy (PML) or current diagnosis of PML.
• Received any investigational drug within 30 days (or 5 half-lives, whichever is shorter) prior to the first dose of the investigational drug.
• 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.
• 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.
• 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.
• 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.
• Received a live-virus vaccine within 28 days prior to the first dose of the investigational drug.
• Known HIV infection.
• Any active major infection (e.g., bacterial, viral, or fungal, including subjects with positive CMV DNA PCR).
• Serologic evidence of active hepatitis B or C infection.
• History of stroke or intracranial hemorrhage within 6 months prior to the first dose of the investigational drug.
• History of bleeding disorders (e.g., hemophilia, Von Willebrand disease).
• Requires or is receiving anticoagulation therapy with warfarin or equivalent vitamin K antagonists.
• 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.
• Pregnancy or breastfeeding.
• Participation in another therapeutic clinical trial.
• Requires proton pump inhibitor therapy (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).
• 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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Sun yat-sen university cancer center, Sun yat-sen university — Guangzhou

Identifiers

NCT: NCT06846489 · B2024-843

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗