Acalabrutinib and rituximab in elderly patients with untreated mantle cell lymphoma (ALTAMIRA)
- Conditions
- Mantle Cell Lymphoma (MCL)
- Registration Number
- 2023-509864-96-00
- Lead Sponsor
- Region Skane
- Brief Summary
To evaluate progression-free survival with acalabrutinib-rituximab in patients with untreated mantle cell lymphoma, compared to data from the NLG-MCL4 trial.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing, recruitment ended
- Sex
- Not specified
- Target Recruitment
- 80
Age ≥60 years
Woman of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception (see appendix 2) during treatment and for 2 days after the last dose of acalabrutinib or for 12 months after last dose of rituximab, whichever is longer
Pathologically confirmed MCL (according to the WHO 2016 classification), with documentation of monoclonal B cells that have a chromosome translocation t(11;14)(q13;q32) and/or overexpress cyclin D1
Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician
No previous treatment for MCL (other than localised radiotherapy or 7-day pulse of steroids for symptom control)
ECOG performance status 0 – 2
Absolute neutrophil count (ANC) > 1.0 x 10^9 and platelet count > 100 x 10^9, unless related to lymphoma - in this situation, the threshold for inclusion is ANC >0.5 x 10^9 and platelet count > 50 x 10^9
Creatinine clearance >30 ml/min (Cockcroft-Gault)
AST and/or ALT <3x ULN and/or P-bilirubin <3x ULN
Able to give voluntary written informed consent
Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL
Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)
Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)
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
Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.
Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.
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
History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug
Breastfeeding or pregnant women
Concurrent participation in another therapeutic clinical trial
History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)
Major surgery within two weeks prior to day 1 of cycle 1
Significant cardiovascular disease such as symptomatic arrhythmias, 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 at Screening. Note: Subjects with controlled, asymptomatic atrial fibrillation are allowed to enroll on study
Received a live virus vaccination within 28 days of first dose of study drug
Patients who are unable to swallow capsules/tablets, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication
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
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)
Active infection requiring treatment
Serious medical or psychiatric illness likely to interfere with participation in this clinical study
Concurrent treatment with another investigational agent outside of this protocol
Known history of drug-specific hypersensitivity or anaphylaxis to rituximab or acalabrutinib (including active product or excipient components)
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Progression-free survival. This is defined as the interval between date of obtaining informed consent and date of documented progression, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive. Progression-free survival. This is defined as the interval between date of obtaining informed consent and date of documented progression, first relapse, or death of any cause. Otherwise, patients will be censored at the last date they were known to be alive.
- Secondary Outcome Measures
Name Time Method Complete response rate at 6 months Complete response rate at 6 months
Molecular remission rate (MRR) by PCR Molecular remission rate (MRR) by PCR
Overall response rate Overall response rate
Progression-free survival (median) Progression-free survival (median)
Response duration (median) Response duration (median)
Duration of molecular remission (median) Duration of molecular remission (median)
Overall survival (median) Overall survival (median)
CR, MRR and ORR in TP53-mutated MCL CR, MRR and ORR in TP53-mutated MCL
Safety, in terms of all grade 3-5 AE Safety, in terms of all grade 3-5 AE
Trial Locations
- Locations (17)
Odense University Hospital
🇩🇰Odense C, Denmark
Region Sjaelland
🇩🇰Roskilde, Denmark
Oulu University Hospital
🇫🇮Oulu, Finland
HUS-Yhtymae
🇫🇮Helsinki, Finland
NU Hospital Group-Vastra Gotalandsregionen
🇸🇪Trollhattan, Sweden
Region Halland
🇸🇪Halmstad, Sweden
Lund University Hospital
🇸🇪Lund, Sweden
Uppsala University Hospital
🇸🇪Uppsala, Sweden
Laenssjukhuset I Kalmar Region Kalmar Laen
🇸🇪Kalmar, Sweden
Region Norrbotten
🇸🇪Lulea, Sweden
Scroll for more (7 remaining)Odense University Hospital🇩🇰Odense C, DenmarkJacob HaaberSite contact+4566113333jacob.h.christensen@rsyd.dk