A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in 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 describe the dose limiting toxicities (DLT) and define the maximum tolerated dose (MTD) of ASP2215 when combined with cytarabine/idarubicin remission induction in a 7+3 schedule. Safety and tolerability of ASP2215 will also be evaluated. This study will also characterize the pharmacokinetics (PK) of ASP2215 when given in combination with cytarabine/idarubicin remission induction and high-dose cytarabine (HiDAC) consolidation therapy in newly diagnosed acute myeloid leukemia as well as evaluate the effect of ASP2215 on the PK of cytarabine.
Detailed Description
This is a two-part trial.

In Part 1, subjects will be enrolled to successive cohorts to determine the maximum tolerated dose (MTD). Dose escalation decision will be made based on DLTs that occur during remission induction. The treatment will consist of three distinct periods: remission induction, consolidation and maintenance.

In Part 2, subjects will be enrolled into an expansion cohort. Subjects will receive ASP2215 at the MTD established in Part 1 or recommended expansion dose, and will also receive remission induction, consolidation and maintenance therapy. The DLT observation period during the expansion cohort will be from the start of the remission induction treatment until Day 21 of the first consolidation cycle or before the start of the second consolidation cycle, whichever is sooner; as well as from the start of maintenance treatment until Day 28 of the second maintenance cycle. If testing at a dose level must be stopped, then a lower dose may be tested for remaining subjects to be enrolled.
Criteria for eligibility
Healthy Volunteers: No
Maximum Age: N/A
Minimum Age: 18 Years
Gender: Both
Criteria: Inclusion Criteria:

- Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to WHO classification (2008) documented within 28 days prior to enrollment.

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

- Subject must meet the following criteria as indicated on the clinical laboratory tests.

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

- Total serum bilirubin ≤ 1.5 x institutional ULN

- Serum creatinine ≤ 1.5 x institutional ULN or an estimated glomerular filtration rate (eGFR) of > 50 ml/min as calculated by the Modification of Diet in Renal Disease (MDRD) equation.

- Subject is suitable for oral administration of study drug.

- Female subject must be either:

- Of non-child bearing potential:

- post-menopausal (defined as at least 1 year without any menses) prior to Screening, or

- documented surgically sterile or status post hysterectomy (at least 1 month prior to Screening)

- Or, if of childbearing potential,

- must agree not to try to become pregnant during the study and for 28 days after the final study drug administration, and

- must have a negative urine pregnancy test at Screening, and

- must use two forms of birth control* (at least one of which must be a barrier method) starting at Screening and throughout the study period and for 28 days after the final study drug administration. *Acceptable forms of birth control include:

1. Established use of oral, injected or implanted hormonal methods of contraception.

2. Placement of an intrauterine device (IUD) or intrauterine system (IUS).

3. Barrier methods of contraception: condom or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository.

- Female subject must not be breastfeeding at Screening or during the study period, and for 28 days after the final study drug administration.

- Female subject must not donate ova starting at Screening and throughout the study period, and for 28 days after the final study drug administration.

- Male subject and their female spouse/partners who are of childbearing potential must be using highly effective contraception consisting of two forms of birth control* (one of which must be a barrier method) starting at Screening and continue throughout the study period and for 90 days after the final study drug administration.

- Male subject must not 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 treatment.

Exclusion Criteria:

- Subject was diagnosed as acute promyelocytic leukemia (APL) or AML with good risk cytogenetics; t(8;21), inv(16) or t(16;16). (Subjects with pending cytogenetics that require treatment may enroll. Any subject that is found to have good risk cytogenetics after initiation of treatment will discontinue ASP2215 and be taken off trial).

- Subject has 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 previous therapy for AML, with the exception of the following:

- Emergency leukapheresis;

- Emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 7 days;

- Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days;

- Growth factor or cytokine support;

- Steroids for the treatment of hypersensitivity or transfusion reactions.

- Subject has clinically active central nervous system leukemia.

- Subject has disseminated intravascular coagulation abnormality (DIC).

- Subject has had major surgery within 4 weeks prior to the first study dose.

- Subject has radiation therapy within 4 weeks prior to the first study dose.

- Subject has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or subject with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.

- Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of cytochrome P450-isoyyme3A4 (CYP3A4) or of P-glycoprotein (P-gp) or substrates of multidrug and toxin extrusion (MATE)1 with the exception of antibiotics, antifungals, and antivirals that are used as standard of care or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject.

- Subject requires treatment with concomitant drugs that target serotonin 5HT1R or 5HT2BR receptors or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.

- Subject has an active uncontrolled infection.

- Subject is known to have human immunodeficiency virus infection.

- Subject has active hepatitis B or C, or other active hepatic disorder.

- Subject has any condition which makes the subject unsuitable for study participation (e.g. ophthalmic conditions such as advanced cataracts).
Locations
University of Kansas Cancer Center
Westwood, Kansas, United States
Status: Recruiting
Johns Hopkins
Baltimore, Maryland, United States
Status: Recruiting
Columbia University Medical Center
New York, New York, United States
Status: Recruiting
University Hopsitals Case Medical Center
Cleveland, Ohio, United States
Status: Recruiting
The Ohio State University
Columbus, Ohio, United States
Status: Recruiting
University of Pennsylvania-Abramson CCC-Dept. of Hem Onc
Philadelphia, Pennsylvania, United States
Status: Recruiting
Texas Transplant Institute
San Antonio, Texas, United States
Status: Recruiting
Start Date
November 2014
Completion Date
March 2020
Sponsors
Astellas Pharma Global Development, Inc.
Source
Astellas Pharma Inc
Record processing date
ClinicalTrials.gov processed this data on July 28, 2015
ClinicalTrials.gov page