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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04996875




Registration number
NCT04996875
Ethics application status
Date submitted
22/07/2021
Date registered
9/08/2021

Titles & IDs
Public title
(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis
Scientific title
A Phase 2 Open-Label, Multicenter Clinical Study of the Safety, Efficacy, Pharmacokinetic, and Pharmacodynamic Profiles of CGT9486 as a Single Agent in Patients With Advanced Systemic Mastocytosis
Secondary ID [1] 0 0
2021-001010-10
Secondary ID [2] 0 0
CGT9486-20-201
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Systemic Mastocytosis (AdvSM) 0 0
SM With an Associated Hematologic Neoplasm (SM-AHN) 0 0
Mast Cell Leukemia (MCL) 0 0
Aggressive Systemic Mastocytosis (ASM) 0 0
Condition category
Condition code
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
Skin 0 0 0 0
Other skin conditions
Blood 0 0 0 0
Other blood disorders
Mental Health 0 0 0 0
Other mental health disorders

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

Experimental: bezuclastinib -


Treatment: Drugs: bezuclastinib
Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM
Timepoint [1] 0 0
18 months
Primary outcome [2] 0 0
Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib
Timepoint [2] 0 0
18 months
Secondary outcome [1] 0 0
Pure Pathologic Response (PPR)
Timepoint [1] 0 0
18 months
Secondary outcome [2] 0 0
Safety of CGT9486 as assessed by incidence of Adverse Events (AEs)
Timepoint [2] 0 0
18 months
Secondary outcome [3] 0 0
To determine the effects of bezuclastinib on mutation allele burden.
Timepoint [3] 0 0
18 months
Secondary outcome [4] 0 0
To determine the effects of bezuclastinib on serum tryptase.
Timepoint [4] 0 0
18 months
Secondary outcome [5] 0 0
To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM.
Timepoint [5] 0 0
18 months
Secondary outcome [6] 0 0
Change from baseline in histopathologic findings in blood and bone marrow
Timepoint [6] 0 0
18 months
Secondary outcome [7] 0 0
Change in spleen and liver volume by imaging
Timepoint [7] 0 0
18 months
Secondary outcome [8] 0 0
Change in Patient Global Impression of Severity (PGIS) scale
Timepoint [8] 0 0
18 months
Secondary outcome [9] 0 0
Change in Patient Global Impression of Change (PGIC) scale
Timepoint [9] 0 0
18 months
Secondary outcome [10] 0 0
Change in Mastocytosis Quality of Life Questionnaire (MC-QoL)
Timepoint [10] 0 0
18 months
Secondary outcome [11] 0 0
Change in Mastocytosis Activity Score (MAS)
Timepoint [11] 0 0
18 months
Secondary outcome [12] 0 0
Duration of Response (DOR)
Timepoint [12] 0 0
18 months
Secondary outcome [13] 0 0
Time to Response (TTR)
Timepoint [13] 0 0
18 months
Secondary outcome [14] 0 0
Progression Free Survival (PFS)
Timepoint [14] 0 0
18 Months
Secondary outcome [15] 0 0
Overall Survival (OS)
Timepoint [15] 0 0
18 months

Eligibility
Key inclusion criteria
Key Inclusion Criteria for Main Study:

1. Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility Committee

1. Aggressive Systemic Mastocytosis (ASM)
2. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
3. Mast Cell Leukemia (MCL)
2. Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study).
3. ECOG (0 to 3)
4. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits

Key
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria for Main Study:

1. Persistent toxicity from previous therapy for AdvSM that has not resolved to = Grade 1
2. Associated hematologic neoplasm requiring immediate antineoplastic therapy
3. Clinically significant cardiac disease
4. Known positivity for the FIP1L1 PDGFRA fusion. Patients with eosinophilia without detectable KIT D816V mutation must demonstrate lack of PDGFRA fusion mutation prior to enrollment
5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
6. History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
7. Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
8. Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening bone marrow biopsy
9. Received hematopoietic growth factor support within 14 days before the first dose of study drug
10. Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug
11. Need for treatment with high dose steroids

Key Inclusion Criteria for Substudy Population:

Rollover Cohort

1. Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving bezuclastinib
2. Demonstrated clinical benefit from bezuclastinib therapy
3. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits

High-Risk Cohort

1. Receiving or indicated for AHN-directed therapy.
2. Diagnosed with one of the following pathologic diagnoses of SM-AHN:

1. Myelodysplastic syndrome (MDS) that is high- or very high-risk
2. Accelerated phase myeloproliferative neoplasm (MPN)
3. MDS with excessive blasts in bone marrow or peripheral blood
4. Chronic myelomonocytic leukemia-2 (CMML-2)
3. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits.

Key Exclusion Criteria for Substudy Population:

1. Diagnosis of Philadelphia chromosome-positive malignancy
2. Diagnosis of acute myeloid leukemia (AML)
3. Appropriate for allogenic hematopoietic stem cell transplantation
4. Any contraindication to selected concomitant therapy
5. Rollover Cohort: Have not demonstrated acceptable tolerability of previous bezuclastinib therapy
6. High-Risk Cohort: Previously treated with investigational therapy for AdvSM
7. High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due to treatment-related toxicity
8. High-Risk Cohort: Received any cytoreductive therapy or any investigational agent less than 14 days, and for cladribine, interferon alpha, pegylated interferon, and any antibody therapy less than 28 days, before screening or archival bone marrow biopsy

Study design
Purpose of the study
Treatment
Allocation to intervention
NA
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
Single group
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
9/11/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/09/2025
Actual
Sample size
Target
140
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [2] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [3] 0 0
Peter MacCallum Cancer Centre - Melbourne N.
Recruitment postcode(s) [1] 0 0
2747 - Kingswood
Recruitment postcode(s) [2] 0 0
4215 - Southport
Recruitment postcode(s) [3] 0 0
3051 - Melbourne N.
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
Arizona
Country [3] 0 0
United States of America
State/province [3] 0 0
California
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
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
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
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Texas
Country [12] 0 0
United States of America
State/province [12] 0 0
Utah
Country [13] 0 0
Austria
State/province [13] 0 0
Vienna
Country [14] 0 0
Belgium
State/province [14] 0 0
Liège
Country [15] 0 0
Canada
State/province [15] 0 0
Alberta
Country [16] 0 0
Canada
State/province [16] 0 0
Ontario
Country [17] 0 0
France
State/province [17] 0 0
Paris
Country [18] 0 0
France
State/province [18] 0 0
Poitiers
Country [19] 0 0
France
State/province [19] 0 0
Toulouse
Country [20] 0 0
Germany
State/province [20] 0 0
Aachen
Country [21] 0 0
Germany
State/province [21] 0 0
Freiburg
Country [22] 0 0
Germany
State/province [22] 0 0
Mannheim
Country [23] 0 0
Italy
State/province [23] 0 0
Bologna
Country [24] 0 0
Italy
State/province [24] 0 0
Florence
Country [25] 0 0
Italy
State/province [25] 0 0
Verona
Country [26] 0 0
Netherlands
State/province [26] 0 0
Groningen
Country [27] 0 0
Norway
State/province [27] 0 0
Oslo
Country [28] 0 0
Spain
State/province [28] 0 0
Barcelona
Country [29] 0 0
Spain
State/province [29] 0 0
Madrid
Country [30] 0 0
Switzerland
State/province [30] 0 0
Basel
Country [31] 0 0
United Kingdom
State/province [31] 0 0
Leeds
Country [32] 0 0
United Kingdom
State/province [32] 0 0
London

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Cogent Biosciences, Inc.
Address
Country

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Rachael Easton, MD, Ph.D.
Address 0 0
Cogent Biosciences, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Hina Jolin, PharmD
Address 0 0
Country 0 0
Phone 0 0
+1 (617) 945-5576
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.


Results not provided in https://clinicaltrials.gov/study/NCT04996875