A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Japanese Patients With Newly Diagnosed Acute Myeloid Leukemia.
Conditions
Acute Myeloid Leukemia
Conditions: official terms
Leukemia - Leukemia, Myeloid - Leukemia, Myeloid, Acute
Conditions: Keywords
ASP2215, Cytarabine, Idarubicin, Acute Myeloid Leukemia
Study Type
Interventional
Study Phase
Phase 1
Study Design
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Intervention
Name: ASP2215 Type: Drug
Name: Idarubicin Type: Drug
Name: Cytarabine Type: Drug
Overall Status
Recruiting
Summary
The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended expansion dose (RED) of ASP2215 concomitant with cytarabine/idarubicin as induction chemotherapy based on the status of the onset of dose-limiting toxicity (DLT) in newly Diagnosed Acute Myeloid Leukemia (AML). Safety and tolerability of ASP2215 will also be evaluated. This study will also characterize the pharmacokinetic (PK) parameters of ASP2215 concomitant with induction and consolidation chemotherapy as well as evaluate the PK parameters of cytarabine concomitant with ASP2215.
Detailed Description
This study is composed of the dose-escalation part and the expansion part. In the dose-escalation part, at least 3 subjects will receive ASP2215 at each dose (low, middle, and high) for determination of MTD and/or RED. Treatment of AML in this study is composed of 3 periods of therapy: remission induction, consolidation, and maintenance. The decision of whether or not to proceed to the next dose will be made based on the occurrence of DLT during Cycle 1 of the induction period.

In the expansion part, a maximum of 6 subjects will receive ASP2215 at RED that has been determined in the dose-escalation part and the safety will be assessed based on the onset of DLTs during Cycle 1 of the induction and consolidation periods.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: 69 Years
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Subject is defined as having previously untreated de novo AML according to the World Health Organization (WHO) criteria (2008) within 28 days prior to study enrollment.

- Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.

- Subject must meet all of the following criteria in the laboratory test at screening:

- Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of ≤ 2.5 × institutional upper limit of normal (ULN)

- Total serum bilirubin level of ≤ 1.5 × institutional ULN

- Serum creatinine level of ≤ 1.5 × institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 mL/min†

- Subject is suitable for oral administration of ASP2215.

- Female subject falls under the following:

- Of non-childbearing potential:

- ・Post-menopausal (defined as at least 1 year with no menses without a medical reason such as drug administration) at screening, or

- ・Documented surgically sterile or status post-hysterectomy (at least 1 month prior to screening)

- Of childbearing potential:

- ・Has a negative result for the pregnancy test at screening, and

- ・Agrees to use an appropriate contraception starting at screening and throughout the study period and for 28 days after the final study drug administration

- Female subject agrees not to breastfeed starting at screening and throughout the study period and for 28 days after the final study drug administration.

- Female subject agrees not to donate ova starting at screening and throughout the study period and for 28 days after the final study drug administration.

- Male subject and his female spouse/partner who is of childbearing potential agrees to use an appropriate contraception starting at screening and throughout the study period and for 90 days after the final study drug administration.

- Male subject agrees not to donate sperm starting at screening and throughout the study period and for 90 days after the final study drug administration.

- Subject agrees not to participate in another interventional study while on study treatment.

- Subject can be admitted during the induction period.

Exclusion Criteria:

- Subject was diagnosed with acute promyelocytic leukemia (APL).

- Subject has breakpoint cluster region-abelson (BCR-ABL)-positive leukemia (chronic myelogenous leukemia in blast crisis).

- Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS).

- Subject has received prior AML treatment except for the following:

- Urgent leukapheresis

- Hydroxyurea administration for emergency treatment of hyperleukocytosis (≤ 7 days)

- Administration of retinoic acid before the diagnosis to exclude APL (≤ 7 days)

- Supportive care using growth factors or cytokines

- Steroid administration to treat hypersensitivity or blood transfusion reactions

- Subject has clinically active central nervous system leukemia.

- Subject has disseminated intravascular coagulation (DIC).

- Subject has had major surgery within 28 days prior to the first study drug administration.

- Subject has had radiation therapy within 28 days prior to the first study drug administration.

- Subject has congestive heart failure of New York Heart Association (NYHA) class 3 or 4, or subject with a past history of congestive heart failure of NYHA class 3 or 4 and in whom echocardiogram (ECHO) or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of < 45%.

- Subject has cardiac impairment or a clinically significant cardiac disease, including any one of the following:

- Complete left bundle branch block

- Obligate use of a cardiac pacemaker

- Congenital long QT syndrome

- Prolongation of the QTc interval (> 480 ms) on electrocardiogram (ECG) at screening

- Right bundle branch block + left anterior hemiblock (bifascicular block)

- Angina pectoris within 3 months prior to study drug administration

- Acute myocardial infarction within 3 months prior to study drug administration

- Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of CYP3A4, with the exception of antibiotics, antifungals, and antivirals that are considered absolutely essential for prevention or treatment of infections and for which the physician judged that there are no interchangeable drugs.

- Subject requires treatment with concomitant drugs that target serotonin 5HT1 or 5HT2B receptors or sigma receptors, with the exception of drugs that are considered absolutely essential for treatment of the subject.

- Subject has an active uncontrollable infection.

- Subject is known to have human immunodeficiency virus (HIV) infection.

- Subject has active hepatitis B or C or other active hepatic disorders.

- Subject has any condition that, in the investigator's or sub-investigator's opinion, makes the subject unsuitable for study participation.
Locations
Chubu, Japan
Status: Recruiting
Kanto, Japan
Status: Recruiting
Kyusyu, Japan
Status: Recruiting
Start Date
October 2014
Completion Date
October 2017
Sponsors
Astellas Pharma Inc
Source
Astellas Pharma Inc
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page