A Phase II Study of Crenolanib Besylate in Subjects With Relapsed/Refractory Acute Myeloid Leukemia With FLT3 Activating Mutations
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Overall Response Rate
研究概览
简要总结
This is a Phase II open label study of crenolanib besylate. This study will enroll subjects with relapsed or refractory AML with FLT3 activating mutations. Prior treatment with other FLT3 TKIs is allowed. Subjects will take crenolanib 200mg/m2/day divided in three doses daily (preferably every eight hours), taken orally at least 30 minutes pre or post meal until disease progression, death, or the patient discontinues treatment for adverse events, investigator's judgment, or other reasons. Patients who are able to proceed to allogeneic stem cell transplant will be able to resume crenolanib therapy post-transplant in an attempt to maintain remission.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Relapsed/refractory primary AML or AML secondary to antecedent hematologic disorder with an expected survival of 3 months or greater
- •Patients must have tested positive for FLT3-ITD and /or other FLT3 activating mutations within < 60 days of the screening period.
- •Age ≥18 years
- •ECOG PS 0 - 2
- •Adequate liver function, defined as total or direct bilirubin ≤1.5x ULN, ALT ≤3.0x ULN,AST ≤3.0x ULN. Exceptions for ALT and AST restrictions will be made in the setting of documented liver involvement with leukemia
- •Adequate renal function, defined as serum creatinine ≤1.5x ULN
- •Recovery from non-hematological toxicities of prior therapy (including HSCT) to no more than grade 1 (except alopecia)
- •Subjects should have received no anti-leukemic therapy (except hydroxyurea) prior to the first dose of crenolanib as follows: for 14 days for classical cytotoxic agents and for five times the t1/2 (half-life) for FLT3 inhibitors and antineoplastic agents that are neither cytotoxic nor FLT3 inhibitors (e.g. hypomethylating agent or MEK inhibitor)
- •Negative pregnancy test for women of childbearing potential
- •Able and willing to provide written informed consent
- •Subjects who received crenolanib prior to and are within 30-90 days of an allogeneic stem cell transplant (HSCT) and have either no active GVHD where therapy has been initiated or GVHD where therapy has not been escalated within 14 days prior to start of study drug
排除标准
- •Absence of FLT3 activating mutation
- •<5% blasts in blood or marrow at screening
- •Concurrent chemotherapy, systemic immunosuppressants, or targeted anti-cancer agents,other than hydroxyurea
- •Patient with concurrent severe and/or uncontrolled medical conditions that in the opinion of the investigator may impair the participation in the study or the evaluation of safety and/or efficacy
- •HIV infection or active hepatitis B manifested as hepatitis surface antigen positive (HepBsAg) or hepatitis C manifested as hepatitis C antibody positive
- •For post HSCT, subjects who are within 29 days of an allogeneic transplant, and/or are on an unstable dose of immunosuppressive drugs for management or prophylaxis of GVHD or have escalated therapy for GVHD within 14 days of starting study drug and/or have >/=Grade 2 persistent non hematological toxicity related to the transplant or did not receive crenolanib prior to HSCT
- •Evidence of lack of engraftment if post allogeneic transplant
- •Unable to swallow pills
- •Major surgical procedures within 14 days of Cycle 1 Day 1 administration of crenolanib
- •Unwillingness or inability to comply with protocol.
研究组 & 干预措施
Crenolanib Besylate
干预措施: Crenolanib Besylate (CP-868,596-26) (Drug)
结局指标
主要结局
Overall Response Rate
时间窗: From the date of first dose to the end of protocol treatment, 1 year.
To determine the response rate to crenolanib.Complete remission (CR) response criteria include a post-baseline bone marrow (BM) biopsy or aspiration % blasts \<5%, absolute neutrophil count (ANC) \>1×10\^9/L and platelet count \>100×10\^9/L. CRi response included all CR criteria met, except participant did not experience either platelet recovery or ANC recovery. Partial Response (PR) response included a decrease of ≥50% in % blasts in the BM aspirate or biopsy from baseline but \>5%. Hematologic improvement (HI) response included erythroid response where Hgb increased ≥ 1.5 g/dL, platelet response where platelets increased ≥ 30 x 10\^9/L for patient starting with \>20 x 10\^9/L platelets or increase from \<20 x 10\^9/L to \>20 x 10\^9/L and by at least 100% and neutrophil response where at least 100% increase and an increase \>0.5 x 10\^9/L. Resistant Disease (RD) was defined as the absence of CR, CRi, CRp, PR or HI.
次要结局
未报告次要终点