Clinical trial • Phase II • Haematology
ACALABRUTINIB for Mantle cell lymphoma
Phase II trial of ACALABRUTINIB for Mantle cell lymphoma.
Overview
- Trial Therapeutic Area
- Haematology
- Trial Disease
- Mantle cell lymphoma
- Trial Stage
- Phase II
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 07-08-2024
- First CTIS Authorization Date
- 04-09-2024
Trial design
None/Not specified (study evaluates acalabrutinib + rituximab in patients with untreated MCL and compares results to historical data from the NLG-MCL4 trial)-controlled Phase II trial across 17 sites in Denmark, Finland, Sweden and others.
- Comparator
- None/Not specified (study evaluates acalabrutinib + rituximab in patients with untreated MCL and compares results to historical data from the NLG-MCL4 trial)
- Target Sample Size
- 80
Eligibility
Recruits 80 No vulnerable populations selected (isVulnerablePopulationSelected: false). Participants must be able to give voluntary written informed consent as stated in the inclusion criteria..
- Pregnancy Exclusion
- Breastfeeding or pregnant women
- Vulnerable Population
- No vulnerable populations selected (isVulnerablePopulationSelected: false). Participants must be able to give voluntary written informed consent as stated in the inclusion criteria.
Inclusion criteria
- {"criterion_text":"- Age ≥60 years\n- 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\n- Stage II-IV, measurable by imaging and requiring treatment in the opinion of the treating clinician\n- No previous treatment for MCL (other than localised radiotherapy or 7-day pulse of steroids for symptom control)\n- ECOG performance status 0 – 2\n- 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\n- Creatinine clearance >30 ml/min (Cockcroft-Gault)\n- AST and/or ALT <3x ULN and/or P-bilirubin <3x ULN\n- Able to give voluntary written informed consent\n- 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"}
Exclusion criteria
- {"criterion_text":"- Patients considered fit enough to undergo autologous or allogeneic stem cell transplant for MCL\n- Major surgery within two weeks prior to day 1 of cycle 1\n- Patients who are unable to swallow capsules/tablets, or who have disease significantly affecting gastrointestinal function that would limit oral absorption of medication\n- 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\n- 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)\n- Active infection requiring treatment\n- Serious medical or psychiatric illness likely to interfere with participation in this clinical study\n- Concurrent treatment with another investigational agent outside of this protocol\n- Known history of drug-specific hypersensitivity or anaphylaxis to rituximab or acalabrutinib (including active product or excipient components)\n- Active bleeding, history of bleeding diathesis (eg, hemophilia or von Willebrand disease)\n- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura)\n- 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\n- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, phenprocoumon) within 7 days of first dose of study drug.\n- Prothrombin time/INR or aPTT (in the absence of Lupus anticoagulant) > 2x ULN.\n- 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\n- History of significant cerebrovascular disease or event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug\n- Breastfeeding or pregnant women\n- Concurrent participation in another therapeutic clinical trial\n- History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML)\n- 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"}
Endpoints
Primary endpoints
- {"endpoint_text":"- 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.","definition_or_measurement_approach":"Defined as interval between date of obtaining informed consent and date of documented progression, first relapse, or death from any cause; censoring at last known alive date."}
Secondary endpoints
- {"endpoint_text":"- Complete response rate at 6 months","definition_or_measurement_approach":"Complete response assessed at 6 months"}
- {"endpoint_text":"- Molecular remission rate (MRR) by PCR","definition_or_measurement_approach":"Assessed by PCR (molecular remission rate)"}
- {"endpoint_text":"- Overall response rate","definition_or_measurement_approach":""}
- {"endpoint_text":"- Progression-free survival (median)","definition_or_measurement_approach":"Median progression-free survival"}
- {"endpoint_text":"- Response duration (median)","definition_or_measurement_approach":"Median duration of response"}
- {"endpoint_text":"- Duration of molecular remission (median)","definition_or_measurement_approach":"Median duration of molecular remission"}
- {"endpoint_text":"- Overall survival (median)","definition_or_measurement_approach":"Median overall survival"}
- {"endpoint_text":"- CR, MRR and ORR in TP53-mutated MCL","definition_or_measurement_approach":"Subgroup analyses in TP53-mutated MCL"}
- {"endpoint_text":"- Safety, in terms of all grade 3-5 AE","definition_or_measurement_approach":"Safety assessed by incidence of all grade 3-5 adverse events"}
Recruitment
- Planned Sample Size
- 80
- Recruitment Window Months
- 84
- Consent Approach
- Participants must be able to give voluntary written informed consent. Subject information and informed consent forms are provided (documents present for Denmark: L1_SIS and ICF_DK; Finland: L1_SIS and ICF_FI; Sweden: L1_SIS and ICF_SE; Norway: L1_SIS and ICF_NO). No assent procedure or minor consent processes are indicated; vulnerable population not selected.
Geography
- Total Number Of Sites
- 17
- Total Number Of Participants
- 80
Denmark
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 10-09-2024
- Processing Time Days
- 19
- Number Of Sites
- 2
- Number Of Participants
- 13
Sites
- Site Name
- Odense University Hospital
- Department Name
- Department of Hematology
- Contact Person Name
- Jacob Haaber
- Contact Person Email
- jacob.h.christensen@rsyd.dk
- Site Name
- Region Sjaelland
- Department Name
- Department
- Contact Person Name
- Sif Gudbrandsdottir
- Contact Person Email
- sgu@regionsjaelland.dk
Finland
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 04-09-2024
- Processing Time Days
- 13
- Number Of Sites
- 2
- Number Of Participants
- 6
Sites
- Site Name
- Oulu University Hospital
- Department Name
- Department of Hematology
- Contact Person Name
- Hanne Kuitunen
- Contact Person Email
- hanne.kuitunen@pohde.fi
- Site Name
- HUS-Yhtymae
- Department Name
- Department of Hematology
- Contact Person Name
- Annika Pasanen
- Contact Person Email
- annika.pasanen@hus.fi
Sweden
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 05-09-2024
- Processing Time Days
- 14
- Number Of Sites
- 9
- Number Of Participants
- 45
Sites
- Site Name
- NU Hospital Group-Vastra Gotalandsregionen
- Department Name
- Department of Hematology
- Contact Person Name
- Lina Wide
- Contact Person Email
- lina.wide@vgregion.se
- Site Name
- Region Halland
- Department Name
- Department of Medicine
- Contact Person Name
- Nevzeta Kuric
- Contact Person Email
- nevzeta.kuric@regionhalland.se
- Site Name
- Lund University Hospital
- Department Name
- Department of Oncology
- Contact Person Name
- Mats Jerkeman
- Contact Person Email
- mats.jerkeman@med.lu.se
- Site Name
- Uppsala University Hospital
- Department Name
- Department of Oncology
- Contact Person Name
- Ingrid Glimelius
- Contact Person Email
- ingrid.glimelius@igp.uu.se
- Site Name
- Laenssjukhuset I Kalmar Region Kalmar Laen
- Department Name
- Department of Internal Medicine
- Contact Person Name
- Fredrik Ellin
- Contact Person Email
- fredrik.ellin@regionkalmar.se
- Site Name
- Region Norrbotten
- Department Name
- Department of Medicine
- Contact Person Name
- Lena Brandefors
- Contact Person Email
- lena.brandefors@norbotten.se
- Site Name
- Sahlgrenska University Hospital-Vaestra Goetalandsregionen
- Department Name
- Department of Hematology and Coagulation
- Contact Person Name
- Martin Stenson
- Contact Person Email
- martin.stenson@vgregion.se
- Site Name
- Karolinska University Hospital
- Department Name
- Center of Hematology
- Contact Person Name
- Kristina Sonnevi
- Contact Person Email
- kristina.sonnevi@regionstockholm.se
- Site Name
- Region Vaesterbotten
- Department Name
- Cancercentrum
- Contact Person Name
- Karin Papworth
- Contact Person Email
- karin.papworth@regionvasterbotten.se
Norway
- Earliest CTIS Part Ii Submission Date
- 22-08-2024
- Latest Decision Or Authorization Date
- 12-09-2024
- Processing Time Days
- 21
- Number Of Sites
- 4
- Number Of Participants
- 16
Sites
- Site Name
- Helse Stavanger HF
- Department Name
- Department of Oncology
- Contact Person Name
- Idun Bakke Bø
- Contact Person Email
- idun.bakke.bo@sus.no
- Site Name
- Helse Bergen HF
- Department Name
- Department of Oncology
- Contact Person Name
- Anne Turid Bjørnevik
- Contact Person Email
- anne.turid.bjornevik@helse-bergen.no
- Site Name
- Oslo University Hospital HF
- Department Name
- Department of Oncology
- Contact Person Name
- Jon Riise
- Contact Person Email
- jonrii@ous-hf.no
- Site Name
- St. Olavs Hospital HF
- Department Name
- Department of Oncology
- Contact Person Name
- Karin Fahl Wader
- Contact Person Email
- karin.inger.martina.fahl.wader@stolav.no
Sponsor
Primary sponsor
- Full Name
- Region Skane
- Organisation Type
- Hospital/Clinic/Other health care facility
- Country Of Registered Address
- Sweden
Third parties
- {"country":"Finland","full_name":"Oulu University Hospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Finland","full_name":"HUS-Yhtymae","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Norway","full_name":"Oslo University Hospital HF","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Norway","full_name":"Helse Bergen HF","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Norway","full_name":"St. Olavs Hospital HF","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Denmark","full_name":"Odense University Hospital","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Hospital/Clinic/Other health care facility"}
- {"country":"Sweden","full_name":"Croak AB","duties_or_roles":"sponsorDuties code: 1","organisation_type":"Pharmaceutical company"}
Investigational products
- Investigational Product Name
- ACALABRUTINIB
- Active Substance
- ACALABRUTINIB
- Modality
- Small molecule
- Routes Of Administration
- ORAL
- Route
- ORAL
- Maximum Dose
- 200 mg per day
- Combination Treatment
- Yes
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