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

Primary Purpose

Chronic Lymphocytic Leukemia

Status
Active
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
Ceralasertib
Acalabrutinib
Sponsored by
Acerta Pharma BV
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Lymphocytic Leukemia

Eligibility Criteria

18 Years - 130 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
  • Research Site
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  • Research Site

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Experimental

Arm Label

Arm A Part 1 and 2

Arm B Part 1 and 2

Arm Description

DISCONTINUED (ceralasertib monotherapy)

ceralasertib + acalabrutinib in combination

Outcomes

Primary Outcome Measures

Number of participants experiencing dose-limiting toxicities
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.

Secondary Outcome Measures

Full Information

First Posted
October 30, 2017
Last Updated
June 7, 2023
Sponsor
Acerta Pharma BV
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1. Study Identification

Unique Protocol Identification Number
NCT03328273
Brief Title
A Study of AZD6738 and Acalabrutinib in Subjects With Relapsed or Refractory Chronic Lymphocytic Leukemia (CLL)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 31, 2018 (Actual)
Primary Completion Date
September 7, 2021 (Actual)
Study Completion Date
June 30, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Acerta Pharma BV

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Lymphocytic Leukemia

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm A Part 1 and 2
Arm Type
Other
Arm Description
DISCONTINUED (ceralasertib monotherapy)
Arm Title
Arm B Part 1 and 2
Arm Type
Experimental
Arm Description
ceralasertib + acalabrutinib in combination
Intervention Type
Drug
Intervention Name(s)
Ceralasertib
Other Intervention Name(s)
AZD6738
Intervention Description
An ATP competitive, orally bioavailable inhibitor of the Serine/Threonine protein kinase Ataxia Telangiectasia and Rad3 related (ATR).
Intervention Type
Drug
Intervention Name(s)
Acalabrutinib
Other Intervention Name(s)
ACP196
Intervention Description
An experimental anti-cancer drug and Bruton's tyrosine kinase (BTK) inhibitor.
Primary Outcome Measure Information:
Title
Number of participants experiencing dose-limiting toxicities
Description
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.
Time Frame
28 Days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
130 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Acerta Clinical Trials
Organizational Affiliation
1-888-292-9613; acertamc@dlss.com
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Kraków
ZIP/Postal Code
30-510
Country
Poland
Facility Name
Research Site
City
Łódź
ZIP/Postal Code
93-510
Country
Poland
Facility Name
Research Site
City
Birmingham
ZIP/Postal Code
B9 5SS
Country
United Kingdom
Facility Name
Research Site
City
Bournemouth
ZIP/Postal Code
BH7 7DW
Country
United Kingdom
Facility Name
Research Site
City
Cardiff
ZIP/Postal Code
CF14 4XW
Country
United Kingdom
Facility Name
Research Site
City
Leeds
ZIP/Postal Code
LS9 7TF
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
NW1 2PG
Country
United Kingdom
Facility Name
Research Site
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Facility Name
Research Site
City
Nottingham
ZIP/Postal Code
NG5 1PB
Country
United Kingdom
Facility Name
Research Site
City
Oxford
ZIP/Postal Code
OX3 7LJ
Country
United Kingdom
Facility Name
Research Site
City
Southampton
ZIP/Postal Code
SO16 6YD
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing 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.
IPD Sharing URL
https://astrazenecagroup-dt.pharmacm.com/DT/Home
Links:
URL
https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217111&parentIdentifier=ACE-CL-110&attachmentIdentifier=8cd9b89c-d75b-4b6e-8b0b-ac9b4ff4e6ba&fileName=D5330C00008abbreviatedCSRsynopsis_redacted_Final_26Jan2022.pdf&versionIdentifier=
Description
redacted_CSR_synopsis

Learn more about this trial

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

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