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ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02029443
Recruitment Status : Active, not recruiting
First Posted : January 8, 2014
Last Update Posted : July 20, 2021
Sponsor:
Information provided by (Responsible Party):
Acerta Pharma BV

Tracking Information
First Submitted Date  ICMJE January 6, 2014
First Posted Date  ICMJE January 8, 2014
Last Update Posted Date July 20, 2021
Actual Study Start Date  ICMJE January 30, 2014
Actual Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 6, 2014)
Determine the Maximum Tolerated Dose [ Time Frame: Cycle 1 (28 Days) ]
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ACP-196 (Acalabrutinib), a Novel Bruton Tyrosine Kinase (Btk) Inhibitor, for Treatment of Chronic Lymphocytic Leukemia
Official Title  ICMJE A Phase 1/2, Multicenter, Open-label, and Dose-escalation Study of ACP-196 in Subjects With Chronic Lymphocytic Leukemia, Richter's Syndrome or Prolymphocytic Leukemia
Brief Summary This study is evaluating the safety and efficacy of a new Bruton tyrosine kinase (Btk) inhibitor, acalabrutinib, for the treatment of chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Chronic Lymphocytic Leukemia
  • Small Lymphocytic Lymphoma
  • Richter's Syndrome
  • Prolymphocytic Leukemia
Intervention  ICMJE Drug: acalabrutinib
Study Arms  ICMJE Experimental: acalabrutinib
Intervention: Drug: acalabrutinib
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 30, 2019)
306
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2014)
36
Estimated Study Completion Date  ICMJE July 15, 2026
Actual Primary Completion Date July 15, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Men and women ≥ 18 years of age with a confirmed diagnosis of CLL/SLL, which has relapsed after, or been refractory to, ≥ 2 previous treatments for CLL/SLL.
  2. Must have measurable CLL/SLL defined as ≥ 1 lymph node ≥ 2 cm as measured in the longest diameter.
  3. Active disease meeting ≥ 1 of the following IWCLL 2008 criteria for requiring treatment:

    1. Evidence of progressive marrow failure as manifested by the development of, or worsening of, anemia (hemoglobin < 10 g/dL) and/or thrombocytopenia (platelets < 100,000/μL).
    2. Massive (i.e., ≥ 6 cm below the left costal margin), progressive, or symptomatic splenomegaly.
    3. Massive nodes (i.e., ≥ 10 cm in the longest diameter), progressive, or symptomatic lymphadenopathy.
    4. Progressive lymphocytosis with an increase of > 50% over a 2-month period or a lymphocyte doubling time (LDT) of < 6 months. LDT may be obtained by linear regression extrapolation of absolute lymphocyte counts (ALC) obtained at intervals of 2 weeks over an observation period of 2 to 3 months. In subjects with initial blood lymphocyte counts of < 30 X 109/L (30,000/μL), LDT should not be used as a single parameter to define indication for treatment. In addition, factors contributing to lymphocytosis or lymphadenopathy other than CLL (e.g., infections) should be excluded.
    5. Autoimmune anemia and/or thrombocytopenia that is poorly responsive to standard therapy.
    6. Constitutional symptoms documented in the subject's chart with supportive objective measures, as appropriate, defined as ≥ 1 of the following disease-related symptoms or signs:

    i. Unintentional weight loss ≥ 10% within the previous 6 months before Screening.

    ii. Fevers higher than 100.5°F or 38.0°C for 2 or more weeks before Screening without evidence of infection.

    iii. Night sweats for > 1 month before Screening without evidence of infection.

  4. Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
  5. Agreement to use highly effective methods of contraception during the study and for 2 days after the last dose of study drug if sexually active and able to bear or beget children (see Section 3.7.9 for list of highly effective methods of contraception).
  6. Willing and able to participate in all required evaluations and procedures in this study protocol including swallowing capsules without difficulty.
  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 subject privacy regulations).
  8. Removed at Amendment 11.

Inclusion Criteria for Treatment Subgroups

  1. Treatment Naive only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL, who require treatment per National Cancer Institute (NCI) or International Working Group guidelines and a) do not want to receive chemoimmunotherapy or b) have comorbidities that would preclude chemoimmunotherapy.
  2. Ibrutinib Intolerant only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL who are not tolerating ibrutinib due to ibrutinib-related AEs.
  3. Richter's Syndrome/Prolymphocytic Leukemia Transformation only: Men and women ≥ 18 years of age and biopsy proven diffuse large B cell lymphoma (DLBCL) Richter's transformation or prolymphocytic leukemia transformation.
  4. Ibrutinib R/R only: Men and women ≥ 18 years of age with confirmed diagnosis of CLL/SLL whose best response after 2 cycles of ibrutinib therapy was SD or nonresponse or who initially responded to ibrutinib therapy and now have signs of clinical progression.

Exclusion Criteria:

  1. Prior malignancy, except for adequately treated basal cell, squamous cell skin cancer or in situ cervical cancer. Subjects with other prior malignancies from which the subject has been disease free for ≥ 2 years may be included if approved by the medical monitor.
  2. A life-threatening illness, medical condition or organ system dysfunction which, in the investigator's opinion, could compromise the subject's safety, interfere with the absorption or metabolism of acalabrutinib, or put the study outcomes at undue risk.
  3. 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, or left ventricular ejection fraction (LVEF) ≤ 40%.
  4. Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel, symptomatic inflammatory bowel disease, partial or complete bowel obstruction, or gastric restrictions and bariatric surgery, such as gastric bypass.
  5. Any immunotherapy within 4 weeks of first dose of study drug.
  6. For subjects with recent chemotherapy or experimental therapy the first dose of study drug must occur after 5 times the half-life of the agent(s).
  7. Relapsed after, or refractory to, prior BTK inhibitor therapy (Note: Does not apply to Ibrutinib R/R or Richter's Syndrome Group).
  8. Any history of Richter's transformation (Note: Does not apply to Richter's Syndrome Group).

10. Central nervous system (CNS) involvement by lymphoma. 11. Grade ≥ 2 toxicity (other than alopecia) continuing from prior anticancer therapy including radiation.

12. Known history of human immunodeficiency virus (HIV) or serologic status indicating active hepatitis C virus (HCV) or hepatitis B virus (HBV) infection or any uncontrolled active systemic infection. Subjects with hepatitis B core antibody positive who are surface antigen negative or who are hepatitis C antibody positive will need to have a negative polymerase chain reaction (PCR) result before enrollment. Those who are hepatitis B surface antigen positive or hepatitis B PCR positive and those who are hepatitis C PCR positive will be excluded.

13. Uncontrolled AIHA or ITP defined as declining hemoglobin or platelet count secondary to autoimmune destruction within the screening period or requirement for high doses of steroids (> 20 mg daily of prednisone daily or equivalent).

14. History of stroke or intracranial hemorrhage within 6 months prior to the first dose of study drug.

15. Requires treatment with proton-pump inhibitors (e.g., omeprazole, esomeprazole, lansoprazole, dexlansoprazole, rabeprazole, or pantoprazole).

16. Requires anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of study drug.

17. Major surgery within 4 weeks before first dose of study drug. 18. ANC < 0.75 x 109/L or platelet count < 50 x 109/L unless there is bone marrow involvement.

19. Total bilirubin > 1.5 x ULN (total bilirubin ≤ 2.5 x ULN allowed in subjects with autoimmune hemolytic anemia that is otherwise controlled); and aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 3.0 x ULN unless disease related.

20. Serum amylase > 1.5 x ULN or serum lipase > 1.5 x ULN. 21. Significant screening ECG abnormalities including, 2nd degree AV block type II, 3rd degree block, Grade 2 or higher bradycardia, or QTc ≥ 480 ms.

22. Cardiac troponin I levels above the limit of normal as specified by the manufacturer.

23. Breast feeding or pregnant. 24. History of bleeding diathesis (e.g., hemophilia, von Willebrand disease). 25. Concurrent participation in another therapeutic clinical trial. 26. Estimated creatinine clearance of < 30 mL/min, calculated using the formula of Cockcroft and Gault [(140-Age) • Mass (kg)/(72 • creatinine mg/dL); multiply by 0.85 if female].

27. Presence of a gastrointestinal ulcer diagnosed by endoscopy within 3 months before screening.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02029443
Other Study ID Numbers  ICMJE ACE-CL-001
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Responsible Party Acerta Pharma BV
Study Sponsor  ICMJE Acerta Pharma BV
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Acerta Clinical Trials 1-888-292-9613 acertamc@dlss.com
PRS Account Acerta Pharma BV
Verification Date July 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP