NL-OMON55851招募中2 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 - BLU-285-2202:PATHFINDER
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 3
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional
入排标准
- 年龄范围
- 18 至 99（—）
入选标准
- •1. Patients who are >= 18 years of age.
- •2. Patients must have 1 of the following diagnoses as confirmed by World Health
- •Organization (WHO) diagnostic criteria. Before enrollment, the SSC must confirm
- •the diagnosis of AdvSM (based on Central Pathology Laboratory assessment of
- •BM): • ASM. • SM-AHN. The AHN must be myeloid, with additional criteria defined
- •in the protocol. • 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 measurable C-finding per
- •modified IWG-MRT-ECNM criteria, attributed to SM and evaluable for response
- •assessment unless diagnosis is MCL, which does not require a C-finding.
- •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
- •Patients must have documented evidence of mast cell aggregates in the bone
- •marrow or other extracutaneous organ based on central pathology.
- •Patient must be willing to have follow up biopsies of affected organ(s) to
- •document response.
- •Measurable C-findings:
- •o Cytopenias: • ANC < 1.0 × 10^9/L or • Hemoglobin < 10 g/dL or • Platelet
- •count < 75 × 109/L.
- •NOTE: Cytopenias attributable to prior cytoreductive therapy or causes other
- •than SM may not be used as C-findings. o Symptomatic ascites or pleural
- •effusion requiring medical intervention such as:
- •Use of diuretics (Grade 2) or
- •>= 2 therapeutic paracenteses or thoracenteses (Grade 3) at least 28 days
- •apart over the 12 weeks before
- •C1D-8 and 1 of the procedures is performed during the 6 weeks before C1D-8.
- •o >= Grade 2 abnormalities in direct bilirubin (> 1.5 × upper limit of normal
- •[ULN]), aspartate aminotransferase (AST; > 3.0 × ULN), alanine aminotransferase
- •(ALT; > 3.0 × ULN), or alkaline phosphatase (> 2.5 × ULN) with 1 of the
- •following present:
- •Ascites or
- •Clinically relevant portal hypertension or
- •Liver MC infiltration that is biopsy-proven or
- •No other identified cause of abnormal liver function.
- •o >= Grade 2 hypoalbuminemia (< 3.0 g/dL).
- •o A spleen that is palpable >= 5 cm below the left costal margin.
- •o Transfusion-dependent anemia defined as:
- •Transfusion of >= 6 units packed red blood cells (PRBCs) in the 12 weeks
- •before C1D-8 and
- •Most recent transfusion occurring during the 4 weeks before C1D-8 and
- •Transfusion administered for hemoglobin <= 8.5 g/dL and
- •Reason for transfusion is not bleeding, hemolysis, or therapy-related.
- •6. Patient must have a serum tryptase >= 20 ng/mL.
- •7. Patients receiving cytoreductive therapy within the preceding 12 weeks must
- 另有 5 项未显示
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 14 days, and
- •for cladribine, interferon alpha, pegylated interferon and any antibody therapy
- •(eg, brentuximab vedotin) less than 28 days before obtaining screening BM
- •biopsy for this study. If the patient has progressive disease and it is in the
- •patient's best 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. 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 placement 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 polymerase chain reaction (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. The following are
- •exempt from the 3-year limit: completely resected basal cell and squamous cell
- •skin cancer, curatively treated localized prostate cancer, and completely
- •resected carcinoma in situ of any site. 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/1.73m^2 or creatinine> 1.5 × ULN.
- •oPlatelet 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) >
- •450 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 dise
研究者
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