E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Advanced Systemic Mastocytosis (AdvSM) |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10056453 |
E.1.2 | Term | Aggressive systemic mastocytosis |
E.1.2 | System Organ Class | 100000004864 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Part 1: Dose Optimization - To determine the optimal dose of oral CGT9486 in patients with AdvSM
Part 2: Expansion - To determine the efficacy of CGT9486 at the selected optimal dose in patients with AdvSM
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E.2.2 | Secondary objectives of the trial |
Part 1 (Dose Optimization) and Part 2 (Expansion): - To characterize the safety and tolerability of CGT9486 in patients with AdvSM - To evaluate additional efficacy parameters with CGT9486 in patients with AdvSM - To determine the effects of CGT9486 on serum tryptase - To determine the effects of CGT9486 on KIT D816V mutation allele burden - To evaluate histopathologic response in the blood and bone marrow - To assess the PK of CGT9486 in patients with AdvSM - To assess patient-reported outcomes in patients with AdvSM |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Diagnosed with 1 of the following advanced mastocytosis diagnoses by Eligibility Committee: a. Aggressive Systemic Mastocytosis (ASM) b. Systemic Mastocytosis with an Associated Hematologic Neoplasm (SM-AHN) c. Mast Cell Leukemia (MCL) 2. Measurable disease according to modified IWG-MRT-ECNM criteria 3. ECOG (0 to 3) 4. Have clinically acceptable local laboratory screening results (clinical chemistry, hematology) within certain limits |
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E.4 | Principal exclusion criteria |
1. Persistent toxicity from previous therapy for Advanced Systemic Mastocytosis 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 also lack the PDGFRA fusion mutation prior to enrollment) 5. Seropositive for human immunodeficiency virus (HIV) 1 or 2, positive for hepatitis B surface antigen, or positive for 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 before the first dose of study drug 11. Need for treatment with steroids |
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E.5 End points |
E.5.1 | Primary end point(s) |
Part 1: Dose Optimization -Safety assessments and dose modifications; PK and PD assessments; ORR Part 2: Expansion -ORR |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Defined in the endpoint or according to the time points listed in the Schedule of Assessments and Procedures (Table 1 of the Protocol) and Schedule of Pharmacokinetics, Pharmacodynamics, and Biomarker Assessments (Table 2 of the Protocol) |
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E.5.2 | Secondary end point(s) |
Part 1 (Dose Optimization) and Part 2 (Expansion): -Incidence of AEs, SAEs, and AEs leading to dose modifications, and changes from baseline in laboratory results -DOR -TTR -PFS -OS -PPR -Changes in spleen and liver size -Changes in serum tryptase levels -Changes in levels of KIT D816V mutation allele burden -Change in pathologic findings in the blood and bone marrow -Plasma concentration of CGT9486 -PGIC and change in the following patient-reported outcome measures: PGIS, MC-QoL, and MAS |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Defined in the endpoint or according to the time points listed in the Schedule of Assessments and Procedures (Table 1 of the Protocol) and Schedule of Pharmacokinetics, Pharmacodynamics, and Biomarker Assessments (Table 2 of the Protocol) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Yes |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | Yes |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Tolerability of CGT9486 in patients with AdvSM |
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E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Parallel group design in Part 1 of the study (4 cohorts: different doses of the same drug) |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 22 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Australia |
Canada |
Israel |
United States |
Austria |
France |
Poland |
Netherlands |
Spain |
Switzerland |
Germany |
Italy |
Belgium |
Norway |
United Kingdom |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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The study will continue until all subjects have completed at least 2 years of follow up for overall survival, withdrawn from study participation, been lost to follow-up, or died, whichever occurs first |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 6 |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 6 |