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A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia

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ClinicalTrials.gov Identifier: NCT02236013
Recruitment Status : Recruiting
First Posted : September 10, 2014
Last Update Posted : March 6, 2018
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief 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 or daunorubicin 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 or cytarabine/daunorubicin 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.

Condition or disease Intervention/treatment Phase
Acute Myeloid Leukemia Drug: Gilteritinib Drug: Idarubicin Drug: Cytarabine Drug: Daunorubicin Phase 1

Access to an investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

This is a three-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 after the first dose of ASP2215 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 dosing of ASP2215 during the first 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.

In Part 3, two cohorts will be enrolled to evaluate an alternative anthracycline and ASP2215 schedule. During remission induction, ASP2215 dosing will begin at day 8 and continue for 14 days to day 21. Subjects will be hospitalized during remission induction therapy while receiving chemotherapy.

In cohort 3A, some subjects will be enrolled to receive 7+3 regimen consisting of cytarabine and an alternative antracycline, daunorubicin. During remission induction subjects will receive a 7+3 induction regimen consisting of daunorubicin IV infusion on days 1 through 3 and cytarabine as a continuous infusion on days 1 through 7.

In cohort 3B, some subjects will be enrolled to receive 7+3 regimen consisting of cytarabine and idarubicin at an alternative dosing schedule for ASP2215 during remission induction. During remission induction subjects will receive a 7+3 induction regimen consisting of idarubicin by IV infusion on days 1 through 3 and cytarabine as a continuous infusion on days 1 through 7.

For Part 3, if day 21 bone marrow evaluation shows residual blasts and the bone marrow is not aplastic, a second induction cycle with the same regimen will be given starting at least 7 days after last dose of ASP2215 and no later than day 35 of the first induction cycle. Consolidation and Maintenance therapy follow the same schedule and dosage outlined in Part 1.The DLT observation period for dose escalation decisions will be from the start of ASP2215 administration during the first remission induction treatment until day 42 of the last remission induction treatment cycle or before the start of the first consolidation cycle, whichever is sooner.

A subject that receives less than 80% of the intended dose of any of the study drugs during the remission induction period may be replaced.

Part 3 may be expanded for additional subjects to ensure at least some subjects are FLT3 + in each of the Alternative Anthracycline and Schedule Cohorts.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 70 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1 Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia
Actual Study Start Date : January 7, 2015
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2019


Arm Intervention/treatment
Experimental: ASP2215 Dose Escalation (Part 1)
Successive dose escalation cohorts will determine the maximum tolerated dose (MTD)
Drug: Gilteritinib
Oral
Other Name: ASP2215
Drug: Idarubicin
lyophilized powder administered intravenously
Drug: Cytarabine
solution administered intravenously
Experimental: ASP2215 Dose Expansion (Part 2)
Once the MTD has been established in Part 1, up to 20 subjects will be enrolled into an expansion cohort
Drug: Gilteritinib
Oral
Other Name: ASP2215
Drug: Idarubicin
lyophilized powder administered intravenously
Drug: Cytarabine
solution administered intravenously
Experimental: Alternative Anthracycline and Schedule (Part 3)
In Part 3, two cohorts will be enrolled to evaluate an alternative anthracycline and ASP2215 schedule
Drug: Gilteritinib
Oral
Other Name: ASP2215
Drug: Idarubicin
lyophilized powder administered intravenously
Drug: Cytarabine
solution administered intravenously
Drug: Daunorubicin
solution administered intravenously



Primary Outcome Measures :
  1. Safety and tolerability assessed by development of dose limiting toxicities, adverse events, and define maximum tolerated dose (MTD) [ Time Frame: up to 2.5 years after start of the treatment ]

Secondary Outcome Measures :
  1. Pharmacokinetics profile of ASP2215: AUC24, Cmax, Ctrough and tmax [ Time Frame: Days 8, 11, 17, and 28 for remission induction and Days 1, 2, and 15 for consolidation ]
    Area under the curve at 24 hours (AUC24), maximum concentration (Cmax), minimum concentration (Ctrough), and time after dosing when Cmax occurs (tmax)

  2. Pharmacokinetics of cytarabine: Css [ Time Frame: Days 3 and 8 ]
    Steady state concentration (Css)



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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 180 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 180 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 60 days after the final study drug administration.
  • Female subject must not donate ova starting at Screening and throughout the study period, and for 180 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 120 days after the final study drug administration.
  • Male subject must not donate sperm starting at Screening and throughout the study period and for 120 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 ≤ 10 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 inducers of cytochrome P450 (CYP)3A.
  • Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (P-gp) with the exception of 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).
  • Subject has Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
  • Subject has Long corrected QT interval (QTc) Syndrome at Screening.
  • Subject has hypokalemia and hypomagnesemia at Screening (defined as values below institutional lower limit of normal [LLN]).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02236013


Contacts
Contact: Astellas Pharma Global Development 800-888-7704 ext 5473 Astellas.registration@astellas.com

Locations
United States, California
Site US10003 Recruiting
Los Angeles, California, United States, 90095
United States, Connecticut
Site US10013 Recruiting
New Haven, Connecticut, United States, 06520
United States, Illinois
Site US10004 Recruiting
Chicago, Illinois, United States, 60611
United States, Kansas
Site US10009 Recruiting
Westwood, Kansas, United States, 66205
United States, Maryland
Site US10001 Recruiting
Baltimore, Maryland, United States, 21231
United States, New York
Site US10002 Recruiting
New York, New York, United States, 10032
United States, Ohio
Site US10014 Recruiting
Cleveland, Ohio, United States, 44106
Site US10008 Withdrawn
Columbus, Ohio, United States, 43201
United States, Oklahoma
Site US10019 Recruiting
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Site US10006 Recruiting
Philadelphia, Pennsylvania, United States, 19104
United States, Texas
Site US10010 Recruiting
San Antonio, Texas, United States, 78229
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
Investigators
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.

Responsible Party: Astellas Pharma Global Development, Inc.
ClinicalTrials.gov Identifier: NCT02236013     History of Changes
Other Study ID Numbers: 2215-CL-0103
First Posted: September 10, 2014    Key Record Dates
Last Update Posted: March 6, 2018
Last Verified: March 2018

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
ASP2215
Daunorubicin
Gilteritinib
Acute Myeloid Leukemia
Idarubicin
Cytarabine

Additional relevant MeSH terms:
Leukemia
Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Neoplasms
Cytarabine
Daunorubicin
Idarubicin
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Antiviral Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors