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JOURNAL ONKOLOGIE – STUDIE

(Apex) Bezuclastinib in Patients With Advanced Systemic Mastocytosis

Rekrutierend

NCT-Nummer:
NCT04996875

Studienbeginn:
November 2021

Letztes Update:
05.12.2023

Wirkstoff:
bezuclastinib

Indikation (Clinical Trials):
Leukemia, Neoplasms, Mastocytosis, Mastocytosis, Systemic, Hematologic Neoplasms, Leukemia, Mast-Cell, Aggression

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
Cogent Biosciences, Inc.

Collaborator:
-

Studienleiter

Rachael Easton, MD, Ph.D.
Study Director
Cogent Biosciences, Inc.

Kontakt

Studienlocations
(3 von 35)

Universitätsklinikum Freiburg
79104 Freiburg
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Darmkrebszentrum Universitätsklinikum Mannheim
Theodor-Kutzer-Ufer 1 - 3
68167 Mannheim
DeutschlandRekrutierend» Google-Maps
University of Alabama at Birmingham (UAB) Hospital
35233 Birmingham
United StatesRekrutierend» Google-Maps
City of Hope Comprehensive Cancer Center
91010 Duarte
United StatesRekrutierend» Google-Maps
UCLA Medical Center
90095 Los Angeles
United StatesRekrutierend» Google-Maps
Stanford Cancer Institute
94305 Stanford
United StatesRekrutierend» Google-Maps
Winship Cancer Institute - Emory University
30322 Atlanta
United StatesRekrutierend» Google-Maps
Rush University Medical Center
60612 Chicago
United StatesRekrutierend» Google-Maps
Dana-Farber Cancer Institute
02215 Boston
United StatesRekrutierend» Google-Maps
Columbia University Irving Medical Center
10032 New York
United StatesZurückgezogen» Google-Maps
Cleveland Clinic Taussig Cancer Center
44106 Cleveland
United StatesRekrutierend» Google-Maps
MUSC Health University Medical Center
29425 Charleston
United StatesRekrutierend» Google-Maps
The University of Texas MD Anderson Cancer Center
77030 Houston
United StatesRekrutierend» Google-Maps
Huntsman Cancer Institute - University of Utah Health
84112 Salt Lake City
United StatesRekrutierend» Google-Maps
Gold Coast University Hospital
4215 Southport
AustraliaRekrutierend» Google-Maps
Peter MacCallum Cancer Centre
3051 Melbourne N.
AustraliaRekrutierend» Google-Maps
AKH Wien, Universitatsklinikum
1090 Vienna
AustriaRekrutierend» Google-Maps
University of Alberta Hospital
T6G 2G3 Edmonton
CanadaRekrutierend» Google-Maps
St. Michael's Hospital - Unity Health Toronto
M5B 1W8 Toronto
CanadaRekrutierend» Google-Maps
Centre Hospitalier Universitaire (CHU) de Poitiers
86000 Poitiers
FranceRekrutierend» Google-Maps
Centre Hospitalier Universitaire (CHU) de Toulouse
31300 Toulouse
FranceRekrutierend» Google-Maps
IRCCS Azienda Ospedaliero Universitaria di Bologna
40138 Bologna
ItalyRekrutierend» Google-Maps
University Medical Center Groningen
9713 Groningen
NetherlandsRekrutierend» Google-Maps
Hospital Universitario Vall d'Hebron
08740 Barcelona
SpainRekrutierend» Google-Maps
Institut Català d'Oncologia - Hospital Duran i Reynals
08908 Barcelona
SpainRekrutierend» Google-Maps
Hospital Universitario Ramón y Cajal
28034 Madrid
SpainRekrutierend» Google-Maps
University College London Hospital - NHS Foundation Trust
NW1 2BU London
United KingdomRekrutierend» Google-Maps
Guy's Hospital - NHS Foundation Trust
SE1 9RT London
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Brief 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).

Ein-/Ausschlusskriterien

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 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

Studien-Rationale

Primary outcome:

1. Part I: Identify clinically active and tolerable exposures of bezuclastinib in patients with AdvSM (Time Frame - 18 months)

2. 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)

Secondary outcome:

1. Pure Pathologic Response (PPR) (Time Frame - 18 months):
Months

2. 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

3. To determine the effects of bezuclastinib on mutation allele burden. (Time Frame - 18 months):
Percentage change in KIT D816V

4. To determine the effects of bezuclastinib on serum tryptase. (Time Frame - 18 months):
Percentage change in Serum Tryptase

5. To assess the pharmacokinetics of bezuclastinib in subjects with AdvSM. (Time Frame - 18 months):
Percentage change in plasma concentrations of bezuclastinib

6. 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

7. Change in spleen and liver volume by imaging (Time Frame - 18 months):
Percentage change

8. Change in Patient Global Impression of Severity (PGIS) scale (Time Frame - 18 months):
0 -10 points (higher values represent worse symptom outcomes)

9. Change in Patient Global Impression of Change (PGIC) scale (Time Frame - 18 months):
0 - 7 points (higher values represent better symptom outcomes)

10. Change in Mastocytosis Quality of Life Questionnaire (MC-QoL) (Time Frame - 18 months):
0 - 100 (higher values represent better symptom outcomes)

11. Change in Mastocytosis Activity Score (MAS) (Time Frame - 18 months):
0 - 252 (higher values represent worse symptom outcomes)

12. Duration of Response (DOR) (Time Frame - 18 months):
Months

13. Time to Response (TTR) (Time Frame - 18 months):
Months

14. Progression Free Survival (PFS) (Time Frame - 18 Months):
Months

15. Overall Survival (OS) (Time Frame - 18 months):
Months

Geprüfte Regime

  • bezuclastinib (CGT9486 / PLX9486 / ):
    Bezuclastinib is administered as tablets to be taken orally, continuously in 28-day cycles.

Quelle: ClinicalTrials.gov


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