Mantle Cell Lymphoma (MCL)
Conditions
Interventions
Product Name: acalabrutinib
Pharmaceutical Form: Capsule, hard
Trade Name: Mabthera
Product Name: Mabthera
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: RITUXIMAB
CA
Sponsors
Skåne University Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Age =60 years 2. Pathologically confirmed MCL (according to the 2016 WHO classification),with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1 3. Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician 4. No previous treatment for MCL (other than localised radiotherapy or 7 day pulse of steroids for symptom control) 5. ECOG performance status 0 – 2 6. Absolute neutrophil count (ANC) >1.0x 109 and platelet count >100 x 109, unless related to lymphoma - in this situation, the threshold for inclusion is ANC >0.5x 109 and platelet count >50 x 109 7. Creatinine clearance >30 ml/min (Cockcroft-Gault) 8. AST and/or ALT =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
Exclusion criteria: 1. Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL 2. Major surgery within two weeks prior to day 1 of cycle 1 3. Patients who are unable to swallow capsules, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication. 4. Known serological positivity for HBV, HCV, HIV. Patients who are hepatitis B core antibody (anti-HBc) positive and who are surface antigen negative will need to have a negative polymerase chain reaction (PCR) result. Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded. Patients who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. 5. Diagnosed with or treated for any other malignancy than MCL within 2 years prior to day 1 of cycle 1 (except basal cell carcinoma, cutaneous squamous cell carcinoma or any other in situ malignancy) 6. Active infection requiring treatment 7. Serious medical or psychiatric illness likely to interfere with participation in this clinical study 8. Concurrent treatment with another investigational agent outside of this protocol 9. Known history of drug-specific hypersensitivity or anaphylaxis to rituximab or acalabrutinib (including active product or excipient components). 10. Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease). 11. Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura). 12. The use of strong CYP3A inhibitors within 1 week or strong CYP3A inducers within 3 weeks of the first dose of study drug is prohibited 13. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug. 14. Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN. 15. Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Patients receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study. 16. History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug. 17. Breastfeeding or pregnant women 18. Concurrent participation in another therapeutic clinical trial. 19. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML) 20. Significant cardiovascular disease such as symptomatic arrhytmias, congestive heart failure, or myocardial infarction within 6 months of Screening, or any Class 3 or 4 cardiac disease as defined by the New York Heart Association Functional Classification as Screening. Note: Subjects with controlled asymptomatic atrial fibrillation are allowed to enroll on study 21. Received a live virus vaccination within 28 days of first dose of study drug
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate progression-free survival with acalabrutinib-rituximab in patients with untreated mantle cell lymphoma, compared to data from the NLG-MCL4 trial ;Secondary Objective: To evaluate: • Complete remission rate (CR) • Molecular remission rate (MRR) by PCR • Overall response rate (ORR) • Progression-free survival (PFS) • Duration of response (DOR) • Duration of molecular remission • Overall survival (OS) • Safety • CR, MRR and ORR in TP53-mutated MCL As an exploratory endpoint, we will also compare PFS, OS to the ibrutinib-rituximab arm of the phase 3 ENRICH trial.;Primary end point(s): Progression free survival. This is defined as the interval between randomization date and date of documented progression, first relpse or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive.;Timepoint(s) of evaluation of this end point: Continuously during time from randomization, treatment phase, and follow up phase. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Complete response rate at 6 months • Molecular remission rate by PCR • Overall response rate • Progression-free survival (median) • Response duration (median) • Duration of molecular remission (median) • Overall survival (median) • CR, MRR and ORR in TP53-mutated MCL • Safety, in terms of all grade 3-5 AE;Timepoint(s) of evaluation of this end point: Continuously during time for for registration, treatment phase, and follow up phase. | — |
Countries
Denmark, Finland, Norway, Sweden
Contacts
Public ContactClinical Trial Office
Nordic Lymphoma Group, Dept of Haematology
Outcome results
None listed