- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04566887
Acalabrutinib With R-CHOP in Previously Untreated Mantle Cell Lymphoma
A Phase II Study of Acalabrutinib in Combination With R-CHOP Chemotherapy in Previously Untreated Mantle Cell Lymphoma
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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British Columbia
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Vancouver, British Columbia, Canada, V5Z 4E6
- BC Cancer Agency
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Nova Scotia
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Halifax, Nova Scotia, Canada, B3H 2Y9
- QEII Health Sciences Centre
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Ontario
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Toronto, Ontario, Canada
- Princess Margaret Cancer Centre
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Toronto, Ontario, Canada
- Sunnybrook Research Institute
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Quebec
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Quebec City, Quebec, Canada, G1J 1Z4
- Centre Hospitalier Universitaire de Quebec
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Men and women ≥ 18 years of age deemed eligible for treatment with full-dose R-CHOP and ASCT by the qualified investigator.
- Histologic diagnosis of MCL according to the World Health Organization classification
- Previously untreated MCL with the following exceptions: (a) prior radiotherapy for localized disease, (b) up to 7 days of corticosteroids (prednisone 100mg/day equivalent), (c) up to one dose of single-agent chemotherapy (for example, cyclophosphamide), (d) up to one cycle of R-CHOP or bendamustine-rituximab (BR). Patients with exceptions (c) and (d) are eligible as long as all other eligibility criteria are met AND at least a CT scan and bone marrow biopsy were performed prior to chemotherapy.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1, or 2.
- Presence of at least one radiologically measurable nodal or extranodal mass. A measurable nodal mass must have a longest diameter ≥1.5 cm. A measurable extranodal mass should have a longest diameter ≥1.0 cm.
- Women of childbearing potential (WOCBP) who are sexually active must use highly effective methods of contraception during treatment and up to 12 months after the last dose of rituximab or R-CHOP, or 2 days after the last dose of acalabrutinib, whichever is last administered. Examples of highly effective contraceptive methods include an agreement to remain abstinent (ie, refrain from heterosexual intercourse), bilateral tubal ligation, male sterilization, established proper use of hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. Men who are sexually active must use highly effective methods of contraception during treatment and up to 6 months after the last dose of rituximab or R-CHOP, or 2 days after the last dose of acalabrutinib, whichever is last administered. Men require an agreement to remain abstinent (ie, refrain from heterosexual intercourse) or use a condom, and an agreement to refrain from donating sperm. Periodic abstinence and withdrawal are not acceptable methods of contraception. Fertility preservation options should be discussed.
- Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
- Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information
Exclusion Criteria:
- Secondary central nervous system involvement.
- Prior exposure to a BCR inhibitor (eg, BTK inhibitors, phosphoinositide-3 kinase (PI3K), or Syk inhibitors) or BCL-2 inhibitor.
- Prior malignancy (or any other malignancy requiring active treatment), except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, or other cancer from which the subject has been disease free for ≥ 2 years or which will not limit survival to < 5 years. Subjects receiving adjuvant hormonal therapy for early breast or prostate cancer are eligible.
- Clinically significant cardiovascular disease such as uncontrolled or 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. Subjects with controlled, asymptomatic atrial fibrillation during screening can enroll on study.
- Difficulty with or unable to swallow oral medication, or conditions significantly affecting gastrointestinal function that would limit absorption of oral medication.
- Known history of infection with HIV or any significant active infection (eg, bacterial, viral or fungal), including suspected or confirmed progressive multifocal leukoencephalopathy.
- Known history of drug-specific hypersensitivity or anaphylaxis to study drugs (acalabrutinib and individual components of R-CHOP), including active product or excipient components.
- Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
- Uncontrolled AIHA (autoimmune hemolytic anemia) or ITP (idiopathic thrombocytopenic purpura).
- Requires treatment with a strong cytochrome P450 3A4 (CYP3A4) inhibitor/inducer.
- Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (eg, warfarin).
- Requires treatment with proton pump inhibitors (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Subjects receiving proton pump inhibitors who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study.
- History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study drug.
- Major surgical procedure within 4 weeks of first dose of study drug. Note: If a subject had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study drug.
- Received a live virus vaccination within 28 days of first dose of R-CHOP + acalabrutinib.
Hepatitis B or C serologic status: subjects 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). Those who are hepatitis B surface antigen (HbsAg) positive or hepatitis B PCR positive will be excluded.
Subjects who are hepatitis C antibody positive will need to have a negative PCR result. Those who are hepatitis C PCR positive will be excluded. Subjects with a history of Hepatitis C who received antiviral treatment are eligible as long as PCR is negative.
- ANC <1.0 x109/L (subjects with bone marrow involvement by lymphoma are eligible regardless of ANC)
- Platelets <50 x109/L (subjects with bone marrow involvement by lymphoma are eligible regardless of platelet count)
- Total serum bilirubin >2 times the upper limit of normal (or <3 times for Gilbert's disease or documented hepatic involvement by lymphoma), AST and ALT <3 times the upper limit of normal (or <5 times for documented hepatic involvement by lymphoma)
- Creatinine clearance <30 mL/min.
- PT/INR >2 times the upper limit of normal in the absence of anticoagulants and/or PTT >2 times the upper limit of normal in the absence of anticoagulants.
- Breastfeeding or pregnant. WOCBP must have a serum pregnancy test done a maximum of 7 days prior to treatment initiation and a negative result must be documented prior to recruitment.
- Concurrent participation in another therapeutic clinical trial.
- Evidence of disease (such as severe or uncontrolled systemic diseases, including uncontrolled hypertension and renal transplant) that, in the investigator's opinion, make it undesirable for the patient to participate in the study or that would jeopardize compliance with the protocol.
- Received any investigational drug within 30 days or 5 half-lives (whichever is shorter) before first dose of study drug.
- Current life-threatening illness, medical condition, or organ system dysfunction which, in the Investigator's opinion, could compromise the subject's safety or put the study at risk.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Acalabrutinib with R-CHOP chemotherapy
Acalabrutinib 100mg twice per day orally with standard of care R-CHOP chemotherapy by IV every 21 days for a maximum of six cycles.
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Administered as 100mg tablets.
R-CHOP chemotherapy
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Complete response (CR) rate by PET/CT scan using Lugano Classification for Malignant Lymphoma
Time Frame: 1-2 weeks after completing six cycles (21 days) of R-CHOP + acalabrutinib.
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1-2 weeks after completing six cycles (21 days) of R-CHOP + acalabrutinib.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Adverse events of acalabrutinib and R-CHOP by using CTCAE version 5.0
Time Frame: Baseline through end of study treatment (up to 18 weeks)
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Baseline through end of study treatment (up to 18 weeks)
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Measures of efficacy by using the RECIL 2017 criteria.
Time Frame: Baseline to end of study (up to 2 years)
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Baseline to end of study (up to 2 years)
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Rate of minimal residual disease negativity (MRD) prior to transplant by flow cytometry
Time Frame: Up to 18 weeks
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Up to 18 weeks
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Event-free in patients who discontinue acalabrutinib at the point of MRD negativity prior to transplant by flow cytometry
Time Frame: Baseline to end of study (up to 2 years)
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Baseline to end of study (up to 2 years)
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Changes in scores of partient reported outcomes (PRO) as measured by FACT-Lym
Time Frame: Baseline to end of study (up to 2 years)
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Composed of the FACT-G plus the 15-item Lymphoma Subscale (LymS).
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Baseline to end of study (up to 2 years)
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Overall survival in patients who discontinue acalabrutinib at the point of MRD negativity
Time Frame: Baseline to end of study (up to 2 years)
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Baseline to end of study (up to 2 years)
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Changes in scores of partient reported outcomes (PRO) as measured by FACT-Cog
Time Frame: Baseline to end of study (up to 2 years)
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Participants rated their cognitive function on a scale of 0 to 4 where 0 was never and 4 was several times a day.
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Baseline to end of study (up to 2 years)
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Changes in scores of partient reported outcomes (PRO) as measured by EORTC QLQ-C30
Time Frame: Baseline to end of study (up to 2 years)
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Participants rated their quality of life on a scale of 1 to 4 where 1 was not at all and 4 was very much.
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Baseline to end of study (up to 2 years)
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- OZM-109
- 20-5858 (Other Identifier: UHN)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Mantle Cell Lymphoma
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Northwestern UniversityNational Cancer Institute (NCI); Janssen Scientific Affairs, LLCActive, not recruitingStage III Mantle Cell Lymphoma | Stage IV Mantle Cell Lymphoma | Contiguous Stage II Mantle Cell Lymphoma | Noncontiguous Stage II Mantle Cell Lymphoma | Stage I Mantle Cell LymphomaUnited States
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City of Hope Medical CenterNational Cancer Institute (NCI)CompletedRecurrent Mantle Cell Lymphoma | Stage III Mantle Cell Lymphoma | Stage IV Mantle Cell Lymphoma | Contiguous Stage II Mantle Cell Lymphoma | Noncontiguous Stage II Mantle Cell Lymphoma | Stage I Mantle Cell LymphomaUnited States
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National Cancer Institute (NCI)CompletedStage III Mantle Cell Lymphoma | Stage IV Mantle Cell Lymphoma | Contiguous Stage II Mantle Cell Lymphoma | Noncontiguous Stage II Mantle Cell Lymphoma | Stage I Mantle Cell LymphomaUnited States
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Roswell Park Cancer InstituteNational Comprehensive Cancer NetworkCompletedStage III Mantle Cell Lymphoma | Stage IV Mantle Cell Lymphoma | Stage I Mantle Cell Lymphoma | Stage II Contiguous Mantle Cell Lymphoma | Stage II Non-Contiguous Mantle Cell LymphomaUnited States
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University of WashingtonNational Cancer Institute (NCI); National Comprehensive Cancer NetworkTerminatedRecurrent Mantle Cell Lymphoma | Refractory Mantle Cell Lymphoma | Ann Arbor Stage I Mantle Cell Lymphoma | Ann Arbor Stage II Mantle Cell Lymphoma | Ann Arbor Stage III Mantle Cell Lymphoma | Ann Arbor Stage IV Mantle Cell LymphomaUnited States
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Burzynski Research InstituteWithdrawnRecurrent Mantle Cell Lymphoma | Stage III Mantle Cell Lymphoma | Stage IV Mantle Cell Lymphoma | Contiguous Stage II Mantle Cell Lymphoma | Noncontiguous Stage II Mantle Cell LymphomaUnited States
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BeiGeneRecruitingMantle Cell Lymphoma | Relapsed Mantle Cell Lymphoma | Refractory Mantle Cell Lymphoma (MCL)United States, China, Israel, Belgium, Poland, Spain, Turkey, Brazil, Italy, Canada, United Kingdom, France, Germany, Argentina
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BeiGeneCompletedRefractory Mantle Cell Lymphoma | Relapsed Mantle Cell LymphomaChina
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingMantle Cell Lymphoma | Blastoid Variant Mantle Cell Lymphoma | Pleomorphic Variant Mantle Cell LymphomaUnited States
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M.D. Anderson Cancer CenterNational Cancer Institute (NCI)TerminatedRecurrent Mantle Cell Lymphoma | Recurrent Non-Hodgkin Lymphoma | Refractory Non-Hodgkin Lymphoma | Refractory Mantle Cell Lymphoma | Central Nervous System Lymphoma | Gastric Mantle Cell Lymphoma | Splenic Mantle Cell LymphomaUnited States
Clinical Trials on Acalabrutinib
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AstraZenecaAcerta Pharma, LLCCompletedPharmacokinetics | BioavailabilityUnited States
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AstraZenecaParexelCompletedCOVID-19 | Mantle Cell LymphomaGermany
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Acerta Pharma BVAstraZenecaActive, not recruitingMantle Cell Lymphoma (MCL)United States, Poland, Italy
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Acerta Pharma BVNational Institutes of Health (NIH)Active, not recruitingChronic Lymphocytic Leukemia | Small Lymphocytic LymphomaUnited States
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Acerta Pharma BVAstraZenecaCompletedHepatic Insufficiency | Healthy Subjects | Hepatic ImpairmentUnited States
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AstraZenecaCompletedBioequivalenceUnited States
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AstraZenecaCompletedChronic Lymphocytic Leukemia and Relapsed and Refractory Mantle Cell LymphomaIndia
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Kartos Therapeutics, Inc.RecruitingChronic Lymphocytic Leukemia | Non Hodgkin Lymphoma | Diffuse Large B Cell LymphomaBelgium, Korea, Republic of, United States, United Kingdom, Italy, Switzerland, Australia, France, Poland, Portugal, Czechia
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Acerta Pharma BVActive, not recruitingWaldenström Macroglobulinemia (WM)Spain, United States, United Kingdom, France, Italy, Greece, Netherlands
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PETHEMA FoundationActive, not recruitingChronic Lymphocytic Leukemia- Binet Staging SystemSpain