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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05057494




Registration number
NCT05057494
Ethics application status
Date submitted
16/09/2021
Date registered
27/09/2021

Titles & IDs
Public title
A Study of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Scientific title
A Phase III Prospective, Multicenter, Randomized, Open-Label Trial of Acalabrutinib Plus Venetoclax Versus Venetoclax Plus Obinutuzumab in Previously Untreated Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma
Secondary ID [1] 0 0
2021-003936-10
Secondary ID [2] 0 0
D8220C00027
Universal Trial Number (UTN)
Trial acronym
MAJIC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - High grade lymphoma
Cancer 0 0 0 0
Lymphoma (non Hodgkin's lymphoma) - Low grade lymphoma
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Acalabrutinib
Treatment: Drugs - Venetoclax
Treatment: Drugs - Obinutuzumab

Experimental: Arm A: Acalabrutinib plus Venetoclax (AV) - Participants will receive acalabrutinib and venetoclax orally.

Experimental: Arm B: Venetoclax plus Obinutuzumab (VO) - Participants will receive Venetoclax orally and Obinutuzumab via IV infusion.


Treatment: Drugs: Acalabrutinib
Dose formulation: Capsule or Tablet

Treatment: Drugs: Venetoclax
Dose formulation: Tablet

Treatment: Drugs: Obinutuzumab
Dose formulation: Injection

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Until progressive disease (PD) [assessed Up to 6.6 Years].
Secondary outcome [1] 0 0
Rate of peripheral blood (PB) undetectable minimal residual disease (uMRD) based on a clonoSEQ^®
Timepoint [1] 0 0
Screening (Days -45 through -1); Arm A (AV): Day 28 of Cycles 8, 14 and 24 and post treatment follow up visits; Arm B (VO): Day 28 of Cycles 6, 12 and 24 and post treatment follow up visits
Secondary outcome [2] 0 0
Rate of peripheral blood (PB) and Bone marrow (BM) undetectable minimal residual disease (uMRD) by flow cytometry
Timepoint [2] 0 0
Cycle 14 (each Cycle length 28 days) Day 28 for Arm A (AV); Cycle 12 Day 28 for Arm B (VO) and Post treatment follow-up visits (assessed Up to 6.6 Years)
Secondary outcome [3] 0 0
Overall Survival (OS)
Timepoint [3] 0 0
Date of randomization until death from any cause (Assessed Up to 6.6 Years)
Secondary outcome [4] 0 0
Event-free Survival (EFS)
Timepoint [4] 0 0
Date of randomization until first occurrence of disease progression (Assessed Up to 6.6 Years)
Secondary outcome [5] 0 0
Overall Response Rate (ORR)
Timepoint [5] 0 0
Date of randomization until PD (Assessed Up to 6.6 Years)
Secondary outcome [6] 0 0
Complete Response (CR) rate
Timepoint [6] 0 0
Date of randomization until PD (Assessed Up to 6.6 Years)
Secondary outcome [7] 0 0
Change from baseline in European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30 scales
Timepoint [7] 0 0
For AV: Cycle 1-Cycle 2, Cycle 3-Cycle 14; After End of Treatment (EoT); Post treatment follow-up For VO: Cycle 1 Day 1-21, Cycle 1 Day 22-Cycle 6, Cycle 7-Cycle 24 (Each cycle is 28 days); After EoT, Post treatment follow-up (assessed Up to 6.6 years)
Secondary outcome [8] 0 0
Change from baseline in EORTC QLQ-CLL17 scales
Timepoint [8] 0 0
For AV: Cycle 1-Cycle 2, Cycle 3-Cycle 14; After End of Treatment (EoT); Post treatment follow-up For VO: Cycle 1 Day 1-21, Cycle 1 Day 22-Cycle 6, Cycle 7-Cycle 24 (Each cycle is 28 days); After EoT, Post treatment follow-up (assessed Up to 6.6 years)
Secondary outcome [9] 0 0
Proportion of participants experiencing bruising as measured by the National Cancer Institute (NCI) Patient Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) item for Bruising
Timepoint [9] 0 0
For AV: Cycle 1-Cycle 2, Cycle 3-Cycle 14; After End of Treatment (EoT); Post treatment follow-up For VO: Cycle 1 Day 1-21, Cycle 1 Day 22-Cycle 6, Cycle 7-Cycle 24 (Each cycle is 28 days); After EoT, Post treatment follow-up (assessed Up to 6.6 years)
Secondary outcome [10] 0 0
Proportion of participants reporting each response option of the Patient Global Impression of Benefit-Risk (PGI-BR)
Timepoint [10] 0 0
For AV: Cycle 1-Cycle 2, Cycle 3-Cycle 14 (Each cycle is 28 days); and End of treatment, E/D, disease progression, and post-treatment follow-up visits (assessed up to 6.6 years)
Secondary outcome [11] 0 0
Number of participants with adverse events (AEs)
Timepoint [11] 0 0
From screening (Days -45 through -1) until survival follow-up (Up to 6.6 years)

Eligibility
Key inclusion criteria
1. Participant must be = 18 years at the time of signing the consent form.
2. Documented TN CLL/SLL requiring treatment according to iwCLL guidelines 2018 (Hallek et al 2018).
3. Adequate BM function independent of growth factor or platelet transfusion support within 2 weeks of screening initiation as follows:

1. Absolute neutrophil count = 1.0 × 10 9 /L; absolute neutrophil count = 500 cells/µL (= 0.50 × 109/L) with documented bone marrow (BM) involvement of chronic lymphocytic leukemia (CLL)/ small lymphocytic lymphoma (SLL).
2. Platelet counts = 30 × 10 9 /L; platelet count = 10 × 10 9 /L in participants with documented BM involvement of CLL/SLL.
4. Estimated CrCL of = 30 mL/min calculated by Cockcroft-Gault (using actual body weight) or serum creatinine < 2 × ULN,

Males:

CrCL (mL/min) = Weight (kg) × (140 - Age)/72 × serum creatinine (mg/dL)

Females:

CrCL (mL/min) = Weight (kg) × (140 - Age) × 0.85/72 × serum creatinine (mg/dL)
5. Meet the following laboratory parameters (Upper limit of normal (ULN) is based on institutional standards):

1. Serum AST and ALT = 3 × ULN (Higher thresholds may be allowed if hepatic dysfunction is attributable to CLL/SLL and after discussion with the Sponsor Hematology Safety Knowledge Group).
2. Total bilirubin = 1.5 × ULN, unless directly attributable to Gilbert's syndrome.
6. An ECOG (Eastern Cooperative Oncology Group) performance status performance status of 0 to 2 with no deterioration over the previous 2 weeks prior to baseline or day of first dosing.
7. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
8. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules and tablets without difficulty.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. As judged by the investigator, any evidence of past or current diseases that, in the investigator's opinion, makes it undesirable for the participant to participate in the study or that would jeopardize their safety or compliance with the protocol or would put the study at risk.
2. Clinically 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. Note: Participants with controlled, asymptomatic atrial fibrillation can enroll in the study.
3. Active bleeding or history of bleeding diathesis (eg, hemophilia or von Willebrand disease).
4. Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenic purpura.
5. History of significant cerebrovascular disease/event, including stroke or intracranial hemorrhage, within 6 months before the first dose of study intervention.
6. Child-Pugh B/C liver cirrhosis.
7. History of prior or current malignancy (including but not limited to known central nervous system involvement such as by CLL/SLL, leptomeningeal disease, or spinal cord compression, known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome) that could affect compliance with the protocol or interpretation of results. Possible examples where compliance or data interpretation may not be affected could include the following, per physician discretion.

1. Curatively treated basal cell carcinoma (BCC) or squamous cell carcinoma (SCC) of the skin or carcinoma in situ of the cervix or carcinoma in situ of the prostate at any time prior to study.
2. Other cancers that have been curatively treated from which the participant is disease-free for = 3 years without further treatment.
8. An individual organ system dysfunction limiting the ability to receive the study intervention or any other life-threatening illness, medical condition, or organ system dysfunction that, in the investigator's opinion, could compromise the participants' safety or interfere with the absorption, distribution, metabolism, or excretion of the study interventions (eg, refractory nausea and vomiting, chronic gastrointestinal disease, inability to swallow the formulated product, previous significant bowel resection, or impaired resorption in the gastrointestinal tract).
9. Known history of infection with HIV or any active significant infection (eg, bacterial, viral, or fungal; including participants with positive cytomegalovirus (CMV) DNA PCR). CMV testing at screening must include serologic testing for CMV immunoglobulin G (CMV IgG), CMV immunoglobulin M (CMV IgM), and CMV DNA PCR testing. Participants must have a result for CMV DNA PCR that is negative at screening to be eligible for the study.
10. History of or ongoing confirmed progressive multifocal leukoencephalopathy (PML).
11. Serologic status reflecting active hepatitis B or C infection:

1. Hepatitis serology will include HBsAg, anti-HBs, anti-HBc and anti-HCV. Any participant who is both anti-HBc positive and HBsAg negative will need to have a negative HBV DNA PCR result before randomization and must be willing to undergo this PCR testing during the study. Any participant who is either HBsAg positive or hepatitis B DNA PCR positive will be excluded.
2. Participants who are hepatitis C antibody positive or inconclusive will need to have a negative HCV RNA PCR result before randomization. Those who are hepatitis C PCR positive will be excluded.
12. Any prior CLL/SLL-specific therapies, except prior rituximab if used for autoimmune cytopenias and not as anti-CLL/SLL treatment.
13. Corticosteroid use > 20 mg within 1 week before the first dose of study intervention, except as indicated for other medical conditions, such as autoimmune cytopenias, inhaled steroid for asthma, topical steroid use, or as premedication for administration of study intervention or contrast. Participants requiring steroids at daily doses > 20 mg prednisone equivalent systemic exposure daily, or those who are administered steroids for leukemia control or white blood cell count lowering, are excluded. Of note, participants may receive corticosteroids as doses > 20 mg as per institutional standards for obinutuzumab premedication prior to C1D1.
14. Prior radio- or toxin-conjugated antibody therapy.
15. Prior allogeneic stem cell or autologous transplant.
16. Known history of hypersensitivity or anaphylaxis to study intervention(s), including active product or excipient components.
17. Requires treatment with a strong cytochrome CYP3A4 inhibitor/inducer. 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.
18. Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists (other anticoagulants allowed).
19. Requires treatment with proton pump inhibitors (PPIs) (eg, omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole). Note: Participants receiving PPIs who switch to H2-receptor antagonists or antacids are eligible for enrollment to this study. This criterion applies only to participants receiving acalabrutinib capsules. This PPI exclusion does not apply if the participant is receiving acalabrutinib tablets.
20. Vaccination with live vaccines 28 days prior to registration for study screening.
21. Major surgical procedure within 28 days of first dose of study intervention. Note: If a participant had major surgery, they must have recovered adequately from any toxicity and/or complications from the intervention before the first dose of study intervention.
22. Concurrent participation in another therapeutic clinical trial. Use of investigational agents that interfere with the study intervention(s) within 28 days or 5 half-lives (whichever is longer) prior to registration for study screening.
23. Prothrombin time/INR or activated partial thromboplastin time, in the absence of lupus anticoagulant or attributed to anticoagulant (eg, direct oral anticoagulant), > 2 × ULN.
24. Currently pregnant (confirmed with positive pregnancy test) or breast feeding.
25. Women of childbearing Potential (WOCBP) unless the following criteria are met: A negative pregnancy test at least 30 days before start of study intervention, followed by immediate highly effective contraception; further pregnancy testing will be performed monthly.
26. Fertile men or WOCBP unless the following criteria are met: Willing to use 2 methods of reliable contraception, including one highly effective contraceptive method (Pearl Index < 1) and one additional effective (barrier) method during study intervention and for 2 days after last acalabrutinib dose (for WOCBP), 30 days after last venetoclax dose (fertile men and WOCBP), and 6 months after last obinutuzumab dose for fertile men and 18 months after last obinutuzumab dose for WOCBP.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Clayton
Recruitment hospital [2] 0 0
Research Site - Geelong
Recruitment hospital [3] 0 0
Research Site - Nedlands
Recruitment hospital [4] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
3168 - Clayton
Recruitment postcode(s) [2] 0 0
3220 - Geelong
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment postcode(s) [4] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Maryland
Country [6] 0 0
United States of America
State/province [6] 0 0
Massachusetts
Country [7] 0 0
United States of America
State/province [7] 0 0
Missouri
Country [8] 0 0
United States of America
State/province [8] 0 0
New York
Country [9] 0 0
United States of America
State/province [9] 0 0
North Carolina
Country [10] 0 0
United States of America
State/province [10] 0 0
Ohio
Country [11] 0 0
United States of America
State/province [11] 0 0
Oregon
Country [12] 0 0
United States of America
State/province [12] 0 0
Pennsylvania
Country [13] 0 0
United States of America
State/province [13] 0 0
Tennessee
Country [14] 0 0
United States of America
State/province [14] 0 0
Utah
Country [15] 0 0
United States of America
State/province [15] 0 0
Virginia
Country [16] 0 0
United States of America
State/province [16] 0 0
Washington
Country [17] 0 0
Czechia
State/province [17] 0 0
Hradec Kralove
Country [18] 0 0
Czechia
State/province [18] 0 0
Ostrava - Poruba
Country [19] 0 0
Czechia
State/province [19] 0 0
Pilsen
Country [20] 0 0
France
State/province [20] 0 0
Bobigny Cedex
Country [21] 0 0
France
State/province [21] 0 0
Montpellier Cedex 5
Country [22] 0 0
France
State/province [22] 0 0
Tours
Country [23] 0 0
Hungary
State/province [23] 0 0
Budapest
Country [24] 0 0
Hungary
State/province [24] 0 0
Debrecen
Country [25] 0 0
Poland
State/province [25] 0 0
Bydgoszcz
Country [26] 0 0
Poland
State/province [26] 0 0
Gdansk
Country [27] 0 0
Poland
State/province [27] 0 0
Katowice
Country [28] 0 0
Poland
State/province [28] 0 0
Kraków
Country [29] 0 0
Poland
State/province [29] 0 0
Lublin
Country [30] 0 0
Poland
State/province [30] 0 0
Lódz
Country [31] 0 0
Spain
State/province [31] 0 0
Barcelona
Country [32] 0 0
Spain
State/province [32] 0 0
Palma de Mallorca

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Supporting document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available to whom?
When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.