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A Study of AZD6738 and Acalabrutinib in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)

Sponsor
Acerta Pharma BV (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT03328273
Collaborator
(none)
11
Enrollment
11
Locations
2
Arms
35.5
Anticipated Duration (Months)
1
Patient Per Site
0
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study evaluates the safety, pharmacokinetics, pharmacodynamics and efficacy of acalabrutinib and ceralasertib (known as AZD6738) when taken in combination.

Condition or Disease Intervention/Treatment Phase
Phase 1

Detailed Description

This study is to determine the safety of ceralasertib when given as monotherapy (discontinued) and in combination with acalabrutinib in subjects with R/R CLL and in subjects who have few therapeutic options available to them. As such, this study includes a formal DLT assessment of the first 6-12 subjects dosed in Part 1 of the study. In addition, routine and regular safety monitoring will be undertaken during this study to fully assess safety of ceralasertib given as monotherapy and in combination with acalabrutinib, with toxicity assessment and dose reduction guidelines.

Study Design

Study Type:
Interventional
Actual Enrollment :
11 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Proof-of-Concept Study Investigating AZD6738 Monotherapy and Acalabrutinib in Combination With AZD6738 (ATR Inhibitor) in Subjects With Relapsed or Refractory High-risk Chronic Lymphocytic Leukemia (CLL)
Actual Study Start Date :
Jul 15, 2020
Actual Primary Completion Date :
Sep 7, 2021
Anticipated Study Completion Date :
Jun 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Other: Arm A Part 1 and 2

DISCONTINUED (ceralasertib monotherapy)

Drug: Ceralasertib
An ATP competitive, orally bioavailable inhibitor of the Serine/Threonine protein kinase Ataxia Telangiectasia and Rad3 related (ATR).
Other Names:
  • AZD6738

    		•
    Experimental: Arm B Part 1 and 2

    ceralasertib + acalabrutinib in combination

    Drug: Ceralasertib
    An ATP competitive, orally bioavailable inhibitor of the Serine/Threonine protein kinase Ataxia Telangiectasia and Rad3 related (ATR).
    Other Names:
  • AZD6738

    • Drug: Acalabrutinib
    An experimental anti-cancer drug and Bruton's tyrosine kinase (BTK) inhibitor.
    Other Names:
  • ACP196

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of participants experiencing dose-limiting toxicities [28 Days]

      Arm A (discontinued): When given as monotherapy in subjects with R/R high-risk CLL who have exhausted other therapeutic options according to local/regional standard of care. Arm B: Ceralasertib given in combination with acalabrutinib in subjects with R/R high-risk CLL who are suitable for treatment with a BTK inhibitor and ceralasertib, per investigator's clinical opinion.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 130 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Diagnosis of relapsed or refractory CLL that meets published diagnostic criteria (International Workshop on Chronic Lymphocytic Leukemia [IWCLL] Hallek 2008) and supported/documented by medical records

    • Subjects must be Relapse/Refractory high risk CLL and have exhausted other therapeutic options according to local/regional standard of care

    • Must have received ≥1 prior therapy for treatment of their disease.

    Exclusion Criteria:

    • A diagnosis of ataxia telangiectasia

    • Any prior exposure to an ATR inhibitor or known hypersensitivity to an excipient of the product.

    • Known history of infection with human immunodeficiency virus (HIV).

    • 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 ACP-196 (acalabrutinib) and/or Ceralasertib

    • 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 corrected QT interval (QTc) > 480 msec.

    • Malabsorption syndrome, disease significantly affecting gastrointestinal function, or resection of the stomach or small bowel or ulcerative colitis, symptomatic inflammatory bowel disease, or partial or complete bowel obstruction.

    • Requirement of treatment with proton-pump inhibitors (e.g., 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.

    • Breast feeding or pregnant

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Research Site Kraków Poland 30-510
    2 Research Site Łódź Poland 93-510
    3 Research Site Birmingham United Kingdom B9 5SS
    4 Research Site Bournemouth United Kingdom BH7 7DW
    5 Research Site Cardiff United Kingdom CF14 4XW
    6 Research Site Leeds United Kingdom LS9 7TF
    7 Research Site London United Kingdom NW1 2PG
    8 Research Site London United Kingdom SE5 9RS
    9 Research Site Nottingham United Kingdom NG5 1PB
    10 Research Site Oxford United Kingdom OX3 7LJ
    11 Research Site Southampton United Kingdom SO16 6YD

    Sponsors and Collaborators

    • Acerta Pharma BV

    Investigators

    • Study Director: Acerta Clinical Trials, 1-888-292-9613; acertamc@dlss.com

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Acerta Pharma BV
    ClinicalTrials.gov Identifier:
    NCT03328273
    Other Study ID Numbers:
    • ACE-CL-110
    • NCT05404282
    First Posted:
    Nov 1, 2017
    Last Update Posted:
    Jun 9, 2022
    Last Verified:
    Jun 1, 2022
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:
    Leukemia
    Leukemia, Lymphoid
    Leukemia, Lymphocytic, Chronic, B-Cell
    Acalabrutinib

    Study Results

    No Results Posted as of Jun 9, 2022