Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA
Dates
study started
completion around
Principal Investigator
by Gary Schiller (ucla)

Description

Summary

This is an open-label, two-part Phase 2 study investigating CGT9486 for the treatment of patients with Advanced Systemic Mastocytosis (AdvSM), including patients with Aggressive SM (ASM), SM with Associated Hematologic Neoplasm (SM-AHN), and Mast Cell Leukemia (MCL).

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

Keywords

Advanced Systemic Mastocytosis (AdvSM), SM With an Associated Hematologic Neoplasm (SM-AHN), Mast Cell Leukemia (MCL), Aggressive Systemic Mastocytosis (ASM), Mastocytosis, Systemic Mastocytosis, Advanced Mastocytosis, Aggressive Mastocytosis, Hematologic Neoplasms, Mast Cell, Mast Cell Leukemia, Soft Tissue Neoplasms, Neoplasms by site, Skin Diseases, Immune Complex Diseases, Immune System Diseases, Hypersensitivity, Hematologic Diseases, Leukemia, Myeloid Leukemia, Acute Myeloid Leukemia, SM with Associated Hematologic Neoplasm, AdvSM, ASM, SM-AHN, MCL, Neoplasm, D816V, KIT D816V, AML, bezuclastinib, CGT9486, CGT, PLX, Connective Tissue Neoplasms, Urticaria Pigmentosa, High-risk myelodysplastic syndrome, Chronic myelomonocytic leukemia, Myeloproliferative neoplasm, High-risk myeloid neoplasm, High-risk MDS, MPN, High-risk MPN, Accelerated phase MPN, CMML, Neoplasms, Mast-Cell Leukemia, Aggression

Eligibility

You can join if…

Open to people ages 18 years and up

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

You CAN'T join if...

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

Locations

  • UCLA Medical Center accepting new patients
    Los Angeles California 90095 United States
  • City of Hope Comprehensive Cancer Center accepting new patients
    Duarte California 91010 United States
  • Stanford Cancer Institute accepting new patients
    Stanford California 94305 United States

Lead Scientist at University of California Health

  • Gary Schiller (ucla)
    Professor-in-Residence, Medicine. Authored (or co-authored) 150 research publications

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Cogent Biosciences, Inc.
ID
NCT04996875
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 140 study participants
Last Updated