(Summit) A multi-part, randomized, double-blind, placebo-controlled Phase II clinical study of the safety and efficacy of CGT9486 in patients with non-advanced systemic mastocytosis

Kriterien zur Teilnahme
1. Presence of one of the following diagnoses according to the WHO classification for systemic mastocytosis (SM) of 2016: • ISM, including the bone marrow mastocytosis subvariant • SSM 2. Inadequate control of SM symptoms, defined as a total MAS score of ≥ 26 after stable treatment with ≥ 2 antimediators (i.e., no changes within 14 days) Acceptable antimediator therapies as best supportive care (BSC): − Histamine receptor type 1 antagonist (H1) − Histamine receptor type 2 antagonist (H2) − Cromolyn sodium − Leukotriene receptor antagonist − Corticosteroids (≤ 10 mg/day prednisone or equivalent medication) − Omalizumab - Ketotifen − Proton pump inhibitors 3. Ability to provide written informed consent 4. Ability and willingness to undergo study-related examinations and attend appointments 5. Age ≥ 18 years 6. Performance status according to Eastern Cooperative Oncology Group (ECOG) of 0 to 2 7. Clinically acceptable local laboratory results (clinical chemistry, hematology) within certain limits, as specified below: a. Absolute neutrophil count of ≥ 1000/μl b. Hemoglobin level of ≥ 10 g/dl c. Platelet count of ≥ 100,000/μl d. Values for aspartate aminotransferase and alanine aminotransferase of ≤ 2.5 × the upper limit of normal (ULN) e. Direct bilirubin value of ≤ 1.5 × ULN f. Estimated glomerular filtration rate of ≥ 30 ml/min/1.73 m2 8. For women of childbearing potential (defined as physiologically and anatomically capable of becoming pregnant): confirmation of a negative serum pregnancy test prior to administration of the investigational product and consent to use a highly effective method of contraception with or without barrier during the study treatment period and for 6 weeks after the last dose of the investigational product; for male patients: consent to use an effective barrier method for contraception (i.e., condoms) during the study treatment period and for 6 weeks after the last dose of the investigational product 9. Willingness to maintain stable use of concomitant medications (including oral contraceptives), unless a change is deemed medically necessary by the investigator 10. Ability to swallow tablets (BASEC)

Ausschlusskriterien
1. Persistent toxicity from a prior treatment of NonAdvSM that has not resolved to ≤ Grade 1 2. Diagnosis of one of the following WHO SM classifications: AdvSM including SM-AHN, ASM, MCL, and mast cell sarcoma 3. Diagnosis of skin mastocytosis without systemic involvement 4. Prior treatment with a targeted KIT inhibitor except for approved agents for the treatment of SM 5. Prior treatment with a cytoreductive therapy or investigational product within < 14 days or 5 half-lives of the drug and for cladribine, interferon alpha, pegylated interferon, or antibody therapy within < 28 days or 5 half-lives of the drug (whichever period is longer) 6. Prior radiation therapy or psoralen and ultraviolet A therapy within < 14 days prior to the start of the screening 7. Prior support with hematopoietic growth factors (e.g., granulocyte colony-stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor [GM-CSF], thrombopoietin) within < 14 days prior to the start of the screening 8. Clinically significant heart disease, defined by one of the following criteria: a. Clinically significant arrhythmias and/or need for antiarrhythmic therapy (except beta-blockers or digoxin) (patients with controlled atrial fibrillation are not excluded.) b. Congenital long QT syndrome or concurrent use of medications known to prolong the QT interval c. Significant prolongation of the QT/QTc interval (e.g., repeated documentation of a QTc interval > 480 ms) as baseline d. Clinically significant heart disease or congestive heart failure of > Class II according to the New York Heart Association; patients must not have unstable angina pectoris (angina at rest) or new-onset angina pectoris within the last 3 months or a myocardial infarction within the last 6 months prior to study entry e. Arterial or venous thrombotic or embolic events, such as a cerebrovascular accident (including transient ischemic attacks), deep vein thrombosis, or pulmonary embolism within the last 6 months prior to the start of treatment with the investigational product (except for an adequately treated catheter-related venous thrombosis that occurred more than 1 month prior to the first administration of the investigational product) 9. Any other known serious illness or serious and/or uncontrolled medical condition (e.g., uncontrolled diabetes or active uncontrolled infection) that could affect participation in the study 10. Positive serological test for HIV-1 or 2 antibodies or positive test for hepatitis B surface antigens or core antibodies or hepatitis C virus antibodies (HCV); patients with a positive HCV antibody test may participate after consultation with the medical monitor, provided that no HCV RNA is detectable in a quantitative HCV RNA assay. (BASEC)