Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk CLL

• ClinicalTrials.gov Identifier: NCT02477696
• Recruitment Status: Active, not recruiting
• First Posted: June 23, 2015
• Results First Posted: January 28, 2022
• Last Update Posted: June 16, 2022
• Sponsor: Acerta Pharma BV
• Information provided by (Responsible Party): Acerta Pharma BV

Tracking Information

• First Submitted Date: June 12, 2015
• First Posted Date: June 23, 2015
• Results First Submitted Date: September 10, 2021
• Results First Posted Date: January 28, 2022
• Last Update Posted Date: June 16, 2022
• Actual Study Start Date: July 28, 2015
• Actual Primary Completion Date: September 15, 2020 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 27, 2022)

Progression Free Survival (PFS) by Independent Review Committee (IRC) Assessment [ Time Frame: Randomization to Disease Progression, Death, or Censoring. Assessed for up to 5 years at the time of analysis. ]

The time from date of randomization to the date of first IRC-assessed disease progression or death due to any cause. Progression by IRC is defined per International Workshop on Chronic Lymphocytic Leukemia (IWCLL) 2008 criteria as lymphocyte count >/= 50% from baseline; >/= 50% increase in lymph nodes, liver or spleen; >/= 50% decrease in platelets from baseline or decrease in hemoglobin > 2 g/dL from baseline and related to CLL.

• Original Primary Outcome Measures (submitted: June 22, 2015): Progression-free survival in Arm A compared to Arm B [ Time Frame: 36 months ]

Current Secondary Outcome Measures (submitted: January 27, 2022)

Number of Patients With Atrial Fibrillation [ Time Frame: Date of first dose until 30 days after the last dose of study drug or the start of new anticancer therapy (whichever comes first). Median follow-up was 41 months. ]

Includes MedDRA preferred terms 'atrial fibrillation' and 'atrial flutter'.

Original Secondary Outcome Measures (submitted: June 22, 2015)

• Incidence of treatment-emergent Grade ≥ 3 infections in Arm A versus Arm B [ Time Frame: 36 months ]
• Incidence of Richter's transformation in Arm A versus Arm B [ Time Frame: 36 months ]
• Incidence of Atrial fibrillation in Arm A versus Arm B [ Time Frame: 36 months ]
• Overall survival in Arm A versus Arm B [ Time Frame: 36 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk CLL
• Official Title: A Randomized, Multicenter, Open-Label, Non-Inferiority, Phase III Study of Acalabrutinib (ACP-196) Versus Ibrutinib in Previously Treated Subjects With High Risk Chronic Lymphocytic Leukemia
• Brief Summary: This study is designed to evaluate PFS endpoint for acalabrutinib vs ibrutinib in previously treated chronic lymphocytic leukemia.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Lymphocytic Leukemia

Intervention

• Drug: ACP-196
  acalabrutinib 100 mg BID (Arm A; N=250)
• Drug: ibrutinib
  ibrutinib 420 mg QD (Arm B; N=250)

Study Arms

• Experimental: ACP-196
  acalabrutinib 100 mg BID (Arm A; N=250)
  Intervention: Drug: ACP-196
• Active Comparator: ibrutinib
  ibrutinib 420 mg QD (Arm B; N=250)
  Intervention: Drug: ibrutinib

Publications *

• Kipps TJ. Mining the Microenvironment for Therapeutic Targets in Chronic Lymphocytic Leukemia. Cancer J. 2021 Jul-Aug 01;27(4):306-313. doi: 10.1097/PPO.0000000000000536. Review.
• Byrd JC, Hillmen P, Ghia P, Kater AP, Chanan-Khan A, Furman RR, O'Brien S, Yenerel MN, Illés A, Kay N, Garcia-Marco JA, Mato A, Pinilla-Ibarz J, Seymour JF, Lepretre S, Stilgenbauer S, Robak T, Rothbaum W, Izumi R, Hamdy A, Patel P, Higgins K, Sohoni S, Jurczak W. Acalabrutinib Versus Ibrutinib in Previously Treated Chronic Lymphocytic Leukemia: Results of the First Randomized Phase III Trial. J Clin Oncol. 2021 Nov 1;39(31):3441-3452. doi: 10.1200/JCO.21.01210. Epub 2021 Jul 26.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 14, 2017): 533
• Original Estimated Enrollment (submitted: June 22, 2015): 500
• Estimated Study Completion Date: August 31, 2027
• Actual Primary Completion Date: September 15, 2020 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Men and women ≥ 18 years of age.
• ECOG performance status of 0 to 2.
• Diagnosis of CLL.

• Must have ≥ 1 of the following high-risk prognostic factors:

  • Presence of 17p del by central laboratory.
  • Presence of 11q del by central laboratory.
• Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment
• Must have received ≥ 1 prior therapies for CLL.

• Meet the following laboratory parameters:

  • ANC ≥ 750 cells/μL or ≥ 500 cells/μL in subjects with documented bone marrow involvement, and independent of growth factor support 7 days before assessment.
  • Platelet count ≥ 30,000 cells/μL without transfusion support 7 days before assessment. Subjects with transfusion-dependent thrombocytopenia are excluded.
  • Serum AST/SGOT and ALT/SGPT ≤ 3.0 x ULN.
  • Total bilirubin ≤ 1.5 x ULN.
  • Estimated creatinine clearance ≥ 30 mL/min.

Exclusion Criteria:

• Known CNS lymphoma or leukemia.
• Known prolymphocytic leukemia or history of, or currently suspected, Richter's syndrome.
• Uncontrolled autoimmune hemolytic anemia or idiopathic thrombocytopenia purpura.
• Prior exposure to ibrutinib or to a BCR inhibitor or a BCL-2 inhibitor.
• Received any chemotherapy, external beam radiation therapy, anticancer antibodies, or investigational drug within 30 days before first dose of study drug.
• Prior radio- or toxin-conjugated antibody therapy.
• Prior allogeneic stem cell or autologous transplant.
• Major surgery within 4 weeks before first dose of study drug.
• Prior malignancy, except for adequately treated lentigo maligna melanoma, non-melanomatous skin cancer, in situ cervical carcinoma or other malignancy treated with no evidence of active disease > 3 years before Screening and at low risk for recurrence.
• Significant cardiovascular disease within 6 months of screening.
• Known history of infection with HIV.
• History of stroke or intracranial hemorrhage within 6 months before randomization.
• History of bleeding diathesis.
• Requires or receiving anticoagulation with warfarin or equivalent vitamin K antagonists within 7 days of first dose of study drug.
• Requires treatment with a strong CYP3A inhibitor/inducer.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: Child, Adult, Older Adult
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belgium, Denmark, France, Germany, Hungary, Israel, Italy, Netherlands, New Zealand, Poland, Spain, Turkey, United Kingdom, United States

Administrative Information

• NCT Number: NCT02477696
• Other Study ID Numbers: ACE-CL-006
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

Plan Description

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 Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 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.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the deidentified 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.
• URL: https://astrazenecagroup-dt.pharmacm.com/DT/Home

• Current Responsible Party: Acerta Pharma BV
• Original Responsible Party: Same as current
• Current Study Sponsor: Acerta Pharma BV
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Acerta Clinical Trials; 1-888-292-9613

• PRS Account: Acerta Pharma BV
• Verification Date: May 2022