EUCTR2017-004836-13-DE进行中（未招募）1 期
An Open-label, Single Arm, Phase 2 Study to Evaluate Efficacy and Safety of Avapritinib (BLU-285), A Selective KIT Mutation-targeted Tyrosine Kinase Inhibitor, in Patients with Advanced Systemic Mastocytosis - PATHFINDER
适应症
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 103
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •1. Patients who are = 18 years of age.
- •2. Patients must have 1 of the following diagnoses as confirmed by WHO diagnostic criteria (Appendix 4, Appendix 5, and Appendix 6). Before
- •enrollment, the SSC must confirm the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of BM).
- •The AHN must be myeloid, with the following exceptions that are excluded:
- •Myelodysplastic syndrome that is very high- or high-risk, as defined by the International Prognostic Scoring System for Myelodysplastic
- •Syndromes (Greenberg et al, 2012).
- •A myeloid AHN with = 10% BM or PB blasts.
- •Philadelphia chromosome-positive malignancies.
- •Incidental indolent, low-grade lymphoid AHNs (eg, chronic lymphocytic
- •leukemia) not requiring treatment are eligible.
- •o MCL, including diagnoses with an AHN component.
- •3. Patients with SM-AHN should have received prior treatment for the AHN component of disease if, in the opinion of the Investigator, such
- •therapy was appropriate.
- •4. Patient must have a BM biopsy taken within 56 days of C1D1, assessed by the Central Pathology Laboratory.
- •5. Cohort 1 only: Patient must have at least 1 of the following measurable C-findings, per modified IWG-MRT-ECNM criteria, attributed
- •to SM (Appendix 6, unless diagnosis is MCL, which does not require a Cfinding).
- •Laboratory abnormality C-findings should not be assessed until the required washout period from last cytoreductive therapy has been
- •met. If a C-finding improves during the Screening period, prior to dosing, and no longer meets criteria for evaluability, it can no longer be counted
- •as a C-finding. In addition:
- •Patients must have documented evidence of MC aggregates in
- •the BM or other extracutaneous organ based on central
- •Patients must be willing to have follow up biopsies of affected
- •organ(s) to document response.
- •6. Patient must have a serum tryptase = 20 ng/mL.
- •7. Patients receiving cytoreductive therapy within the preceding 12 weeks must have discontinued therapy due to disease progression,
- •refractory disease, lack of efficacy, or intolerance.
- •8. Patient's non-antineoplastic SM therapies (ie, BSC; eg, H1 and H2 blockers) must be stable (same dose, no new medications for SM) for =
- •14 days C1D-8. This criterion is not applicable if a patient has progressive disease and it is in the patient's best interest to enroll in the
- •study rapidly with Medical Monitor approval.
- •9. If the patient is receiving corticosteroids, the dose must be = 20 mg/d prednisone or equivalent and dose must be stable for = 14 days before
- •C1D-8. This criterion is not applicable if the patient has progressive disease, and it is in the patient's best interest to enroll in the study
- •rapidly with Medical Monitor approval.
- •10. Patient has Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 to 3.
- •11. Patient must be able to give written informed consent.
- •12. Patient must have been previously treated with midostaurin, unless use of midostaurin is medically contraindicated according to the summary of product characteristics. Midostaurin must have been discontinued due to disease progression, refractory disease, lack of efficacy, or intolerance.
- •Are the trial subjects under 18? no
- •Number of subjects for this age range:
- •F.1.2 Adults (18-64 years) yes
- •F.1.2.1 Number of subjects for this age range 62
- •F.1.3 Elderly (>=65 years) yes
- •F.1.3.1 Number of subjects for this age range 41
排除标准
- •1. Patient has received prior treatment with avapritinib.
- •2. Patient has received any cytoreductive therapy (including midostaurin and other TKIs, hydroxyurea, azacitidine) or an investigational agent less than 14days, and for cladribine, interferon alpha, pegylated interferon and any antibody therapy (eg, brentuximab vedotin) less than 28days before obtaining screening BM biopsy for this study. If the patient has prog disease and it is in the pat's best interest to enroll in the study rapidly
- •1 day before the screening BM biopsy with approval from the Medical Monitor. Cytoreductive therapy may not be restarted during Screening or while on study.
- •3. Patient has received prior radiotherapy within 14 days before the screening BM biopsy, unless given to palliate specific sites of disease (eg, bone lesion).
- •4. Patient received any hematopoietic growth factor within 14 days of screening BM biopsy.
- •5. Patient requires therapy with a concomitant medication that is a strong inhibitor, strong inducer, or moderate inducer of CYP3A4 (Appendix 13).
- •6. Patient has had a major surgical procedure within 14 days of the first dose of study drug. Surgical procedures such as central venous catheter placement, BM biopsy, and feeding tube lacement are considered minor surgical procedures.
- •7. Patient is a candidate for allogeneic hematopoietic stem cell transplantation for treatment of SM, in the opinion of the Investigator.
- •8. Patient has eosinophilia and known positivity for the FIP1L1-PGDFRA fusion, unless the patient has demonstrated relapse or PD on prior imatinib therapy. Patients with eosinophilia (> 1.5 × 10^9/L), who do not have a detectable KIT D816 mutation, must be tested for a PDGFRA fusion mutation by fluorescence in situ hybridization (FISH) or PCR.
- •9. Patient has history of another primary malignancy that has been diagnosed or required therapy within 3 years before the first dose of study drug.
- •10. Patient meets any of the following laboratory criteria:
- •o AST or ALT > 3.0 × ULN; no restriction if due to suspected liver infiltration by MCs.
- •o Bilirubin > 1.5 × ULN; no restriction if due to suspected liver infiltration by MCs or Gilbert's disease. (In the case of Gilbert's disease, a direct bilirubin > 2.0 × ULN would be an exclusion.)
- •o Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73m2 or creatinine> 1.5 × ULN.
- •o Platelet count < 50,000/µL (within 4 weeks of the first dose of study drug) or receiving platelet transfusion(s)
- •11. Patient has a QT interval corrected using Fridericia's formula (QTcF) > 480 msec.
- •12. Patient has a history of a seizure disorder (eg, epilepsy) or requirement for antiseizure medication.
- •13. Patient has a history of a cerebrovascular accident or transient ischemic attacks within 1 year before the first dose of study drug.
- •14. Patient has a known risk or recent history (12 months before the first dose of study drug)) of intracranial bleeding (eg, brain aneurysm, concomitant vitamin K antagonist use).
- •15. Patient has a primary brain malignancy or metastases to the brain.
- •16. Patient has clinically significant, uncontrolled cardiovascular disease, including Grade III or IV congestive heart failure according to the New York Heart Association classification; myocardial infarction or unstable angina within the previous 6 months; clinically significant, uncontrolled arrhythmias; or uncontrolled hypertension.
- •17. Patient is unwilling or unable to comply with scheduled visits, drug administration plan, laboratory
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