NL-OMON53678尚未招募2 期
A Phase 1/2, open-label, 2-arm study evaluating BLU-263 as monotherapy and in combination with azacitidine, in patients with KIT altered hematologic malignancies - AZURE: Study of BLU-263 in Advanced SM
适应症
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 6
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
- •All patients:
- •1. Patient is >=18 years of age at the time of signing the informed consent.
- •2. Patient has Eastern Cooperative Oncology Group performance status of 0-2.
- •3. Patient, or legal guardian if permitted by local regulatory authorities,
- •provides informed consent to participate in the study.
- •4. Patient must have a new BM biopsy or may use archival tissue if taken within
- •56 days prior to C1D1.
- •5. Patients receiving antineoplastic therapy within the preceding 12 weeks must
- •have discontinued therapy due to disease progression, refractory disease, lack
- •of efficacy, or intolerance.
- •6. Patient must be willing to have follow-up biopsies of BM and other affected
- •organs to document response.
- •7. Patients treated with 1 prior selective KIT inhibitor (such as avapritinib
- •or CGT9486) will be permitted on study after confirmation of KIT D816V mutation
- •and with written approval of the study Sponsor. Patients who discontinued
- •treatment with a prior selective KIT inhibitor due to a severe AE that was
- •thought to be related to prior treatment will not be eligible to participate in
- •Arm 1 (Monotherapy):
- •A1_1.For Arm 1, patients must have 1 of the following AdvSM diagnoses, based on
- •WHO diagnostic criteria. Before enrollment, the diagnosis of AdvSM must be
- •confirmed based on central pathology laboratory assessment of BM:
- •a.Aggressive SM
- •b.Systemic mastocytosis-AHN that in the opinion of the Investigator is not
- •considered to be a candidate for HMA monotherapy (Appendix 4). Incidental
- •indolent, low-grade lymphoid AHNs (eg, chronic lymphocytic leukemia) not
- •requiring treatment are eligible.
- •c.Mast cell leukemia, including diagnoses with an AHN component, that does not
- •require a C-finding.
- •d.Upon discussion with the Sponsor, other relapsed or refractory hematologic
- •neoplasms with evidence of aberrant KIT or PDGFR may be considered for
- •enrollment (eg, patients with chronic myeloid neoplasms such as subvariants of
- •MDS/MPN that harbor activating KIT exon 17 mutations but do not fulfill the
- •diagnostic criteria of SM-AHN and patients with myeloid/lymphoid neoplasms with
- •PDGFRa/b fusion genes and mutations conferring resistance to imatinib eg, T674I
- •Arm 2 (Combination Therapy):
- •A2_1.For Arm 2, patients must have 1 of the following SM-AHN diagnoses, based
- •on WHO diagnostic criteria. Diagnosis of the AHN component for SM-AHN must be
- •confirmed based on the central pathology laboratory assessment of the BM:
- •a.Chronic myelomonocytic leukemia-2 (per WHO 2016)
- •b.High or very high-risk MDS (per IPSS-R scoring
- •c.Myelodysplastic syndrome/MPN accelerated diagnosis phase as defined by blast
- •count > 10% in BM OR peripheral blood but not meeting diagnostic criteria of AML
- •d.Myelodysplastic syndrome with excessive blasts-2 (10-19% in BM or 5 19% in
- •peripheral blood) (per WHO 2016)
- •e.Complex karyotype or >= 3 adverse risk mutations (per the IPSS-R cytogenic
- •prognostic groups of Poor or Very Poor)
- •f.Upon discussion with the Sponsor and in consultation with the Response
- •Assessment Committee where needed, hematologic neoplasms which are felt to have
- •strong rationale to consider the combination treatment of BLU-263 and HMA may
- •be considered for enrollment (eg, patients with chronic myeloid neoplasms, such
- 另有 1 项未显示
排除标准
- •All Patients:
- •1. Diagnosis of a Philadelphia chromosome positive malignancy.
- •2. Acute myeloid leukemia.
- •3. If the patient is receiving corticosteroids, and the dose has not been
- •stable for >=7 days. This exclusion criterion is not applicable if a patient has
- •disease that is progressing and there is a safety concern around delaying the
- •patient's study enrollment in order to stabilize the steroid dose and it is in
- •the patient's best interest to enroll in the study rapidly. In such cases,
- •patients may be considered for enrollment following Sponsor Medical Monitor
- •4. Within the 14 days prior to enrollment, patient has received any
- •antineoplastic therapy (including midostaurin, avapritinib and other TKIs) or
- •an investigational agent. Before obtaining the Screening BM Biopsy, at least 28
- •days must have elapsed since the most recent dose of Cladribine, interferon
- •alpha, pegylated interferon and any antibody therapy (eg, brentuximab,
- •vedotin). If the site is unsure of the appropriate wash out period for a
- •specific drug product, they should consult the Medical Monitor.
- •5. Patient has received hydroxyurea within 7 days prior to the first dose of
- •6. Have any of the following laboratory abnormalities on last laboratory
- •assessment within 14 days prior to the first dose of initiation of study drug:
- •a. Alanine aminotransferase and AST >3 × ULN; >5 × ULN if associated with
- •clinically suspected liver infiltration by mastocytosis or another disease for
- •which the patient enrolled into the study.
- •b. Total bilirubin >1.5 × ULN; >3 × ULN if associated with liver infiltration
- •by the disease being treated or in the presence of Gilbert's Disease. (In the
- •case of Gilbert's disease, a direct bilirubin >2.0 ULN would be an exclusion.)
- •c. Estimated (Cockcroft-Gault formula) or measured creatinine clearance <40
- •d. Absolute neutrophil count <0.5 × 109/L.
- •7. Patient received prior HMA therapy (e.g., azacitidine, decitabine) for the
- •current diagnosis.
- •8. At the time of enrollment, patient must not be eligible for allogeneic
- •hematopoietic stem cell transplantation, in the opinion of the Investigator.
- •However, patients who may become eligible for transplant after cytoreduction
- •while on study are eligible to participate.
- •9. Patient received prior radiotherapy within 14 days of screening BM biopsy.
- •Prior radiotherapy given to palliate specific sites of disease (eg, bone
- •lesion) may be allowed with written approval of the Sponsor Medical Monitor.
- •10. Patient received any hematopoietic growth factor (except erythropoietin)
- •within 14 days of screening BM biopsy, or requiring growth factors to maintain
- •adequate neutrophil or platelet levels. Those patients maintained on a chronic
- •dose of erythropoietin, whose hemoglobin is stable, and dose of erythropoietin
- •has not been changed in the prior 28 days are allowed on study.
- •11. Patient received >1 prior selective KIT inhibitor (eg, avapritinib or
- •12. Patients who discontinued treatment with a prior selective KIT inhibitor
- •due to a severe AE that was thought to be related to prior treatment will not
- •be eligible to participate in the study.
- •13. Patient requires therapy with a concomitant medication that is a strong
- •inhibitor, strong inducer, or moderate inducer of CYP3A4.
- •14. Patient has had a major surgical pr
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