A Study of Acalabrutinib Plus Venetoclax and Rituximab in Participants With Treatment Naïve Mantle Cell Lymphoma
- Conditions
- Mantle Cell Lymphoma (MCL)
- Registration Number
- NCT05951959
- Lead Sponsor
- AstraZeneca
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Active, not recruiting
- Sex
- All
- Target Recruitment
- 108
Inclusion Criteria:<br><br>Age<br><br> 1. Participant must be = 18 years or the legal age of consent in the jurisdiction in<br> which the study is taking place, whichever is greater, at the time of signing the<br> informed consent.<br><br> Type of Participant and Disease Characteristics<br><br> 2. Histologically documented MCL based on criteria established by the World Health<br> Organization with documentation of chromosomal translocation t(11;14) (q13;q32)<br> and/or overexpression of cyclin D1 in association with other relevant markers (e.g.,<br> CD5, CD19, CD20 or PAX5).<br><br> 3. Clinical Stage II, III, or IV by Ann Arbor Classification and requiring systemic<br> treatment in the opinion of the treating clinician.<br><br> 4. At least 1 measurable site of disease per Lugano Classification for NHL (Appendix<br> K). The site of disease must be > 1.5 cm in the long axis regardless of short axis<br> measurement or > 1.0 cm in the short axis regardless of long axis measurement, and<br> clearly measurable in 2 perpendicular dimensions, as assessed by diagnostic quality<br> CT (MRI may be used for participants who are either allergic to CT contrast media or<br> have renal insufficiency that per institutional guidelines restricts the use of CT<br> contrast media).<br><br> OR Participant with leukemic non-nodal MCL presentation with splenomegaly (spleen<br> >13 cm in length cranial to caudal) and Bone Marrow (BM) involvement.<br><br> 5. Eastern Cooperative Oncology Group PS of 0, 1, or 2 and ECOG PS of 3 if poor PS is<br> due to lymphoma.<br><br> 6. Confirmed availability of sufficient FFPE tumour samples for central laboratory<br> genomic profiling, including TP53 and clone identification for MRD testing per<br> clonoSEQ® assay. Participants with leukemic non-nodal MCL may be enrolled with<br> available BM tissue. For non-nodal leukaemic MCL participants and when nodal or<br> extranodal tissue is not easily accessible and an invasive biopsy will cause a<br> significant risk to the participant, the participant can be enrolled without a<br> tissue biopsy if MCL BM involvement is confirmed by a BM biopsy and sufficient BM<br> biopsy and aspirate provided for TP53 testing, tumour profiling and clone<br> identification for MRD testing.<br><br> 7. Adequate organ and bone marrow function.<br><br>Sex and Contraceptive/Barrier Requirements 8 Male and/or female Contraceptive use by<br>males or females should be consistent with local regulations regarding the methods of<br>contraception for those participating in clinical studies.<br><br> 1. Male participants:<br><br> - Male participants with a female partner of child-bearing potential should use a<br> condom from enrolment, throughout the study until 90 days following the last<br> dose of venetoclax or rituximab, whichever is longer.<br><br> - For non-pregnant potentially childbearing partners, contraception<br> recommendations should also be considered. A male participant must agree to<br> refrain from sperm donation throughout the study until 90 days following the<br> last dose of venetoclax or rituximab, whichever is longer.<br><br> 2. Female participants:<br><br> - Women of childbearing potential must have negative serum pregnancy test result<br> prior to the start of study intervention (Cycle 1 Day 1) and agree to abstain<br> from breastfeeding during study participation and at least 12 months after the<br> last drug administration.<br><br> - Female participants of childbearing potential who are sexually active with a<br> nonsterilized male partner must agree to use at least one highly effective form<br> of birth control from enrolment, throughout the study and at least 2 days after<br> the last dose of acalabrutinib, at least 6 months after the last dose of<br> venetoclax, and at least 12 months after the last dose of rituximab, whichever<br> is longer.<br><br>Informed Consent 9 Capable of giving signed informed consent which includes compliance<br>with the requirements and restrictions listed in the ICF and in this protocol. Informed<br>consent may be given either by the participant or their legally authorised<br>representative.<br><br>10 Provision of signed and dated written Optional Genetic Research Information informed<br>consent prior to collection of samples for optional genetic research that supports the<br>Genomic Initiative.<br><br>Exclusion Criteria:<br><br>Medical Conditions<br><br> 1. Active CNS involvement by lymphoma or leptomeningeal disease<br><br> 2. Current or previous active malignancies requiring anticancer therapy except:<br><br> - adequately treated basal cell or squamous cell skin cancer<br><br> - in situ cancer<br><br> - history of cancer with no evidence of recurrence for = 2 years before enrolment<br><br> - local radiotherapy with a field that does not overlap with sites of current MCL<br> disease and given at least 3 months prior to the screening PET-CT scan and the<br> participant had recovered from any associated toxicity.<br><br> - anti-hormonal therapies are permitted after discussion with the sponsor's<br> medical monitor<br><br> 3. Participants for whom the goal of therapy is tumour debulking before ASCT<br><br> 4. Any severe or life-threatening illness, medical condition (e.g., uncontrolled<br> hypertension, bleeding diathesis), or organ system dysfunction which, in the<br> investigator' opinion, could compromise the participant safety, interfere with the<br> absorption or metabolism of study intervention (acalabrutinib, rituximab,<br> venetoclax) or put the study outcomes at undue risk<br><br> 5. Clinically significant cardiovascular disease such as uncontrolled or untreated<br> symptomatic arrhythmias, congestive heart failure, or myocardial infarction within 6<br> months of screening, or any Class 3 (moderate) or Class 4 (severe) cardiac disease<br> as defined by the New York Heart Association Functional Classification, or QTc > 480<br> msec at screening. Exception: Participants with controlled, asymptomatic atrial<br> fibrillation during screening may enroll.<br><br> 6. Any active uncontrolled infection (bacterial, viral, fungal, or other infection<br> including tuberculosis), defined as exhibiting ongoing signs/symptoms related to the<br> infection and without improvement, despite appropriate antibiotics or other<br> treatment, which in the investigator's opinion makes it undesirable or pose a safety<br> risk for the participant to participate in the study.<br><br> 7. HIV infection. As per standard of care, results of HIV serology should be known<br> prior to start of study intervention. In the acute situation, registration may occur<br> without the results of the HIV serology but must be available prior to start of<br> study intervention<br><br> Excluded Participants: Participants with active HIV infection (i.e., with detectable<br> viral load by PCR) are excluded.<br><br> Included Participants: HIV-positive participants receiving anti-retroviral treatment<br> with undetectable viral load by PCR may be enrolled following discussion with the<br> participant's HIV physician and the sponsor medical monitor. Potential interactions<br> between anti-retroviral medications and study interventions should be considered.<br><br> 8. Serologic status reflecting active hepatitis B or C. As per standard of care,<br> results of hepatitis serology should be known prior to start of study intervention.<br> In the acute situation, enrolment
Not provided
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method MRD-negative CR rate
- Secondary Outcome Measures
Name Time Method MRD-negative CR rate;Overall Response Rate (ORR);Overall Response Rate (ORR);Complete Response (CR) rate;Complete Response (CR) rate;Duration of Response (DoR);Time to Next Treatment (TTNT);Progression-free Survival (PFS);Event Free Survival (EFS);Overall Survival (OS);Post randomization time to first occurrence of relapse or death, EFS and TTNT in continued acalabrutinib arm compared to observation arm.;Number of participants with any Adverse Events (AE), Serious Adverse Events (SAE), Adverse Event of Special Interest (AESI) and AEs leading to study treatment discontinuation or dose modification.