NCT03563560已完成1 期
A Phase 1 Clinical Study of DSP-2033 (Alvocidib) in Combination With Cytarabine/Mitoxantrone or Cytarabine/Daunorubicin (7+3) in Patients With Acute Myeloid Leukemia
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 10
- 试验地点
- 11
- 主要终点
- To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0
研究概览
简要总结
This is an open label, multi-center, phase 1 study of DSP-2033 (Alvocidib) in combination with cytarabine/mitoxantrone (ACM regimen) or cytarabine/daunorubicin (A+7+3 regimen) in patients with acute myeloid leukemia (AML).
详细描述
This study consists of 2 cohorts of the ACM regimen part for Japanese relapsed/refractory AML patients and 1 cohort of the A+7+3 regimen part for Japanese newly diagnosed AML patients. The purpose of this study are as below.
- To evaluate the safety of DSP-2033 (Alvocidib) in combination with cytarabine/mitoxantrone (ACM regimen) in Japanese patients with relapsed or refractory AML and to confirm its tolerability.
- To evaluate the safety of DSP-2033 （Alvocidib) in combination with cytarabine/daunorubicin (A+7+3 regimen) in Japanese newly diagnosed AML patients and to confirm its tolerability.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
盲法说明
Open labeled
入排标准
- 年龄范围
- 20 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •[For all parts]
- •Japanese patients diagnosed with AML by the 4th edition of WHO criteria.
- •Patients aged between 20 and 64 at acquisition of informed consent.
- •Have received an adequate explanation of the objectives/contents of the clinical study, anticipated therapeutic effects/pharmacology, and risks to his/her understanding, and voluntarily provide written informed consent to participation in the clinical study.
- •Have an Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 2 at entry.
- •Have a left ventricular ejection fraction (LVEF) ≥ 50% determined by echocardiography or multigated acquisition (MUGA) scan within 14 days prior to entry.
- •Have an arterial oxygen saturation (SpO2) ≥ 90% within 14 days prior to entry.
- •The laboratory test within 14 days prior to entry (for multiple tests, the most recent before the entry) meet the following criteria for major organ function.
- •Serum creatinine ≤ 1.5 x the upper limit of normal (ULN) of the institutional reference standard
- •AST and ALT ≤ 2 x ULN of the institutional reference standard
- •Total bilirubin ≤ 2.0 mg/dL
- •Female patients of childbearing potential must have negative pregnancy test results at entry.
- •Female patients or patients with partners of childbearing potential must agree to use an appropriate method of contraception for a period between acquisition of informed consent and 6 months (180 days) after the final dose so that patients or female partners would not become pregnant.
- •[ACM regimen part] In addition to the inclusion criteria for all parts, patients must meet the following criterion.
- •AML patients who could not attain remission after 1 or 2 cycles of potent chemotherapy with anthracycline, cytarabine, and etoposide, or potent chemotherapy with anthracycline and cytarabine. Or patients with 1st or 2nd recurrent AML after complete remission following initial therapy.
- •[A+7+3 regimen part] In addition to the inclusion criteria for all parts, patients must meet the following criterion
- •Treatment naive AML patients.
排除标准
- •[For all parts]
- •Diagnosed with acute promyelocytic leukemia (APL) (FAB classification: M3).
- •Received a transplantation such as hematopoietic stem cell transplant.
- •Have active central nervous system (CNS) leukemia.
- •Complicated by ≥ Grade 3 infection as specified in Common Terminology Criteria for Adverse Events version 4.03 (CTCAE v4.03).
- •HIV antibody, HBs antigen, or HCV antibody tested positive within 90 days prior to entry.
- •Have New York Heart Association (NYHA) cardiac function classification III or IV heart disease or a history, ≥ Grade 3 arrhythmia, angina pectoris or abnormal electrocardiogram (ECG) findings as specified in CTCAE v4.03 or a history of these above.
- •Have a disease that may interfere with the study treatment, such as interstitial pneumonia, pulmonary fibrosis, or active tuberculosis.
- •Complicated by uncontrolled disseminated intravascular coagulation.
- •Have other active malignancies (synchronous multiple malignancies and metachronous multiple malignancies with a disease-free interval not more than 5 years. However, carcinoma in situ that is determined to be cured by local treatment or lesions equivalent to mucosal carcinoma are not included in active multiple malignancies.)
- •Have an uncontrolled complication.
- •Complicated by mental deficits or have a history of mental deficits. However, patients who are able to comply with the study protocol can be included at the discretion of a physician.
- •Complicated by varicella.
- •Received any previous treatment with DSP-2033 or other CDK inhibitors.
- •Received any investigational product or post-marketing clinical study drug within 3 months (90 days) prior to entry.
- •Pregnant or lactating women*)
- •*) If a lactating woman agrees to discontinue breast feeding between acquisition of informed consent and 6 months (180 days) after the final dose, she could be included in the study.
- •Patients who are determined to be inappropriate for participation in this study by the investigator or subinvestigator.
- •[ACM regimen part] In addition to the exclusion criteria cfor all parts, patients who meet any one of the following criteria 17 to 21 will be excluded from the ACM regimen part.
- •Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose, exceeds 360 mg/m2 (body surface area) at entry.
- •Received other leukemia treatment within 21 days prior to entry.
- •Have a history of radiation therapy on the mediastinum.
- •Have sustained ≥ Grade 2 adverse drug reaction (except alopecia) as specified in CTCAE v4.03, which developed by the previous treatment.
- •Have a history of hypersensitivity against any one of cytarabine, mitoxantrone, or contained excipients.
- •[A+7+3 regimen part] In addition to the exclusion criteria for all parts, patients who meet any one of the following criteria 22 to 23 will be excluded from the A+7+3 regimen part.
- •Have the cumulative total exposure of anthracycline, daunorubicin-equivalent dose, exceeds 100 mg/m2 (body surface area) at entry.
- •Have a history of hypersensitivity against any one of cytarabine, daunorubicin, or contained excipients.
研究组 & 干预措施
ACM regimen
Experimental
ACM regimen is for Japanese patients with relapsed or refractory AML.
干预措施: Alvocidib (Drug)
ACM regimen
Experimental
ACM regimen is for Japanese patients with relapsed or refractory AML.
干预措施: Cytarabine (Drug)
ACM regimen
Experimental
ACM regimen is for Japanese patients with relapsed or refractory AML.
干预措施: Mitoxantrone (Drug)
A+7+3 regimen
Experimental
A+7+3 regimen is for Japanese newly diagnosed AML patients.
干预措施: Alvocidib (Drug)
A+7+3 regimen
Experimental
A+7+3 regimen is for Japanese newly diagnosed AML patients.
干预措施: Cytarabine (Drug)
A+7+3 regimen
Experimental
A+7+3 regimen is for Japanese newly diagnosed AML patients.
干预措施: Daunorubicine (Drug)
结局指标
主要结局
To evaluate safety and tolerability in Japanese AML patients by CTCAE v4.0
时间窗: 2 months
Safety and tolerability of DSP-2033 (Alvocidib) in combination with cytarabine/mitoxantrone (ACM regimen) in Japanese patients with relapsed or refractory AML and in combination with cytarabine/daunorubicin (A+7+3 regimen) in Japanese newly diagnosed AML patients. Safety and tolerability analyses:The number of subjects with treatment-related adverse events as assessed by CTCAE v4.0. The number of subjects with DLT and incidence rate during the DLT evaluation period.
次要结局
- To evaluate the Anti-tumor effects based on bone-marrow blasts(2 months)
- To evaluate peak plasma concentration (Cmax) of ACM regimen and A+7+3 regimen in Japanese(14 days)
- To evaluate Area under the plasma concentration versus time curve (AUC) of ACM regimen and A+7+3 regimen in Japanese(14 days)
- Event-free survival (EFS) (ACM regimen part only)(12 months)
- Overall survival (OS) (ACM regimen part only)(12 months)
研究者
研究点 (11)
Loading locations...
相似试验
已完成
1 期
A Phase 1 Clinical Study of DSP-2033 (Alvocidib) in Combination with Cytarabine/Mitoxantrone or Cytarabine/Daunorubicin (7+3) in Patients with Acute Myeloid LeukemiaAcute Myeloid LeukemiaJPRN-jRCT2080223907Sumitomo Dainippon Pharma Co., Ltd.10
终止
1 期
Alvocidib in Treating Patients With Metastatic or Unresectable Refractory Solid Tumors or Hematologic MalignanciesHematopoietic/Lymphoid CancerUnspecified Adult Solid Tumor, Protocol SpecificNCT00070239National Cancer Institute (NCI)100
终止
1 期
Cyclophosphamide, Alvocidib, and Rituximab in Treating Patients With High Risk B-Cell Chronic Lymphocytic Leukemia or Small Lymphocytic LymphomaRecurrent Small Lymphocytic LymphomaRefractory Chronic Lymphocytic LeukemiaStage I Chronic Lymphocytic LeukemiaStage I Small Lymphocytic LymphomaStage II Chronic Lymphocytic LeukemiaStage II Small Lymphocytic LymphomaStage III Chronic Lymphocytic LeukemiaStage III Small Lymphocytic LymphomaStage IV Chronic Lymphocytic LeukemiaStage IV Small Lymphocytic LymphomaChronic Lymphocytic LeukemiaProlymphocytic LeukemiaNCT01076556National Cancer Institute (NCI)9
已完成
1 期
Alvocidib, Oxaliplatin, Fluorouracil, and Leucovorin Calcium in Treating Patients With Advanced Solid TumorsUnspecified Adult Solid Tumor, Protocol SpecificNCT00080990National Cancer Institute (NCI)46
已完成
2 期
Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid LeukemiaAdult Acute Basophilic LeukemiaAdult Acute Eosinophilic LeukemiaAdult Acute Megakaryoblastic Leukemia (M7)Adult Acute Minimally Differentiated Myeloid Leukemia (M0)Adult Acute Monoblastic Leukemia (M5a)Adult Acute Monocytic Leukemia (M5b)Adult Acute Myeloblastic Leukemia With Maturation (M2)Adult Acute Myeloblastic Leukemia Without Maturation (M1)Adult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Adult Acute Myelomonocytic Leukemia (M4)Adult Erythroleukemia (M6a)Adult Pure Erythroid Leukemia (M6b)Secondary Acute Myeloid LeukemiaUntreated Adult Acute Myeloid LeukemiaNCT00407966National Cancer Institute (NCI)45