(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis
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ClinicalTrials.gov Identifier: NCT04996875 |
Recruitment Status :
Recruiting
First Posted : August 9, 2021
Last Update Posted : December 5, 2023
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Condition or disease | Intervention/treatment | Phase |
---|---|---|
Advanced Systemic Mastocytosis (AdvSM) SM With an Associated Hematologic Neoplasm (SM-AHN) Mast Cell Leukemia (MCL) Aggressive Systemic Mastocytosis (ASM) | Drug: bezuclastinib | Phase 2 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 140 participants |
Allocation: | N/A |
Intervention Model: | Single Group Assignment |
Intervention Model Description: | There are two parts to this study, including Part I, Dose Optimization, and Part II Expansion. Part II is separated into two stages. |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official 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 |
Actual Study Start Date : | November 9, 2021 |
Estimated Primary Completion Date : | January 2025 |
Estimated Study Completion Date : | September 2025 |
Arm | Intervention/treatment |
---|---|
Experimental: bezuclastinib |
Drug: bezuclastinib
Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.
Other Names:
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- Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM [ Time Frame: 18 months ]
- Part II: - Determine efficacy of bezuclastinib as measured by mIWG Objective Response Rate (ORR) - Confirm the exposure-response relationship of bezuclastinib [ Time Frame: 18 months ]
- Pure Pathologic Response (PPR) [ Time Frame: 18 months ]Months
- Safety of CGT9486 as assessed by incidence of Adverse Events (AEs) [ Time Frame: 18 months ]Incidence of AEs according to CTCAE version 5.0 or higher
- To determine the effects of bezuclastinib on mutation allele burden. [ Time Frame: 18 months ]Percentage change in KIT D816V
- To determine the effects of bezuclastinib on serum tryptase. [ Time Frame: 18 months ]Percentage change in Serum Tryptase
- To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM. [ Time Frame: 18 months ]Percentage change in plasma concentrations of bezuclastinib
- Change from baseline in histopathologic findings in blood and bone marrow [ Time Frame: 18 months ]Percentage change in mast cell infiltration in the bone marrow and percentage change in eosinophilia and monocytosis in the blood
- Change in spleen and liver volume by imaging [ Time Frame: 18 months ]Percentage change
- Change in Patient Global Impression of Severity (PGIS) scale [ Time Frame: 18 months ]0 -10 points (higher values represent worse symptom outcomes)
- Change in Patient Global Impression of Change (PGIC) scale [ Time Frame: 18 months ]0 - 7 points (higher values represent better symptom outcomes)
- Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) [ Time Frame: 18 months ]0 - 100 (higher values represent better symptom outcomes)
- Change in Mastocytosis Activity Score (MAS) [ Time Frame: 18 months ]0 - 252 (higher values represent worse symptom outcomes)
- Duration of Response (DOR) [ Time Frame: 18 months ]Months
- Time to Response (TTR) [ Time Frame: 18 months ]Months
- Progression Free Survival (PFS) [ Time Frame: 18 Months ]Months
- Overall Survival (OS) [ Time Frame: 18 months ]Months
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Key Inclusion Criteria for Main Study:
-
Diagnosed with one of the following advanced mastocytosis diagnoses by Eligibility Committee
- Aggressive Systemic Mastocytosis (ASM)
- Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN)
- Mast Cell Leukemia (MCL)
- Measurable disease according to modified IWG-MRT-ECNM criteria. (A subset of patients inevaluble per mIWG-MRT-ECNM will be included in the study).
- ECOG (0 to 3)
- Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
Key Exclusion Criteria for Main Study:
- Persistent toxicity from previous therapy for AdvSM that has not resolved to ≤ Grade 1
- Associated hematologic neoplasm requiring immediate antineoplastic therapy
- Clinically significant cardiac disease
- 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
- Seropositive for human immunodeficiency virus (HIV) 1 or 2, or positive for hepatitis B surface antigen or hepatitis C virus (HCV) antibody
- History of clinically significant bleeding event within 30 days before the first dose of study drug or need for therapeutic anticoagulation on study
- Diagnosed with or treated for malignancy other than the disease under study within the prior 3 years before enrollment
- 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
- Received hematopoietic growth factor support within 14 days before the first dose of study drug
- Received strong CYP3A4 inhibitors or inducers within 14 days or 5 drug half-lives, whichever is longer, before the first dose of study drug
- Need for treatment with high dose steroids
Key Inclusion Criteria for Substudy Population:
Rollover Cohort
- Demonstrate AHN progression requiring immediate AHN-directed therapy while receiving bezuclastinib
- Demonstrated clinical benefit from bezuclastinib therapy
- Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits
High-Risk Cohort
- Receiving or indicated for AHN-directed therapy.
-
Diagnosed with one of the following pathologic diagnoses of SM-AHN:
- Myelodysplastic syndrome (MDS) that is high- or very high-risk
- Accelerated phase myeloproliferative neoplasm (MPN)
- MDS with excessive blasts in bone marrow or peripheral blood
- Chronic myelomonocytic leukemia-2 (CMML-2)
- Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits.
Key Exclusion Criteria for Substudy Population:
- Diagnosis of Philadelphia chromosome-positive malignancy
- Diagnosis of acute myeloid leukemia (AML)
- Appropriate for allogenic hematopoietic stem cell transplantation
- Any contraindication to selected concomitant therapy
- Rollover Cohort: Have not demonstrated acceptable tolerability of previous bezuclastinib therapy
- High-Risk Cohort: Previously treated with investigational therapy for AdvSM
- High-Risk Cohort: Previously treated with cytoreductive therapy and discontinued due to treatment-related toxicity
- 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04996875
Contact: Hina Jolin, PharmD | +1 (617) 945-5576 | ApexInfo@cogentbio.com |
Study Director: | Rachael Easton, MD, Ph.D. | Cogent Biosciences, Inc. |
Responsible Party: | Cogent Biosciences, Inc. |
ClinicalTrials.gov Identifier: | NCT04996875 |
Other Study ID Numbers: |
CGT9486-20-201 2021-001010-10 ( EudraCT Number ) |
First Posted: | August 9, 2021 Key Record Dates |
Last Update Posted: | December 5, 2023 |
Last Verified: | November 2023 |
Individual Participant Data (IPD) Sharing Statement: | |
Plan to Share IPD: | No |
Studies a U.S. FDA-regulated Drug Product: | Yes |
Studies a U.S. FDA-regulated Device Product: | No |
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