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Trial record 1 of 1 for:    2215-CL-0301: NCT02421939
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A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02421939
Recruitment Status : Active, not recruiting
First Posted : April 21, 2015
Last Update Posted : May 24, 2019
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Brief Summary:

The purpose of this study is to determine the clinical benefit of ASP2215 therapy in patients with FMS-like tyrosine kinase (FLT3) mutated acute myeloid leukemia (AML) who are refractory to or have relapsed after first-line AML therapy as shown with overall survival (OS) compared to salvage chemotherapy, and to determine the efficacy of ASP2215 therapy as assessed by the rate of complete remission and complete remission with partial hematological recovery (CR/CRh) in these patients.

This study will also determine the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy.

Condition or disease Intervention/treatment Phase
Leukemia, Acute Myeloid (AML) Drug: gilteritinib Drug: LoDAC (Low Dose Cytarabine) Drug: Azacitidine Drug: MEC (Mitoxantrone, Etoposide, Cytarabine) Drug: FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin) Phase 3

Expanded Access : An investigational treatment associated with this study is available outside the clinical trial.   More info ...

Detailed Description:

Subjects considered an adult according to local regulations at the time of signing informed consent may participate in this study. Subjects will be randomized in a 2:1 ratio to receive ASP2215 or salvage chemotherapy. Subjects will enter the screening period up to 14 days prior to the start of treatment. Prior to randomization, a salvage chemotherapy regimen will be pre-selected for each subject; options will include low-dose cytarabine (LoDAC), azacitidine, mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC), or fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) with idarubicin (FLAG-IDA). The randomization will be stratified by response to first-line therapy and pre-selected salvage chemotherapy. Subjects will be administered treatment over continuous 28-day cycles.

After treatment discontinuation, subjects will have a pre-hematopoietic stem cell transplant (HSCT)/end-of-treatment visit within 7 days after treatment discontinuation, followed by a 30-day follow-up for safety, in which a telephone contact with the subject is sufficient unless any assessment must be repeated for resolution of treatment-related adverse events (AEs). After that, long term follow-up will be done every 3 months up to 3 years from the subject's end-of-treatment visit.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 371 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 3 Open-Label, Multicenter, Randomized Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FLT3 Mutation
Actual Study Start Date : October 20, 2015
Actual Primary Completion Date : September 17, 2018
Estimated Study Completion Date : December 2020

Arm Intervention/treatment
Experimental: ASP2215
Administered once daily
Drug: gilteritinib
tablet, oral
Other Names:
  • ASP2215

Active Comparator: Salvage chemotherapy
Options for salvage chemotherapy are limited to the following: Low- Dose Cytarabine (LoDAC), Azacitidine, MEC Induction Chemotherapy, FLAG-IDA Induction Chemotherapy
Drug: LoDAC (Low Dose Cytarabine)
subcutaneous (SC) or intravenous (IV) injection

Drug: Azacitidine
SC or IV injection

Drug: MEC (Mitoxantrone, Etoposide, Cytarabine)
IV injection

Drug: FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin)
SC (G-CSF) and IV (Fludarabine, Cytarabine, Idarubicin) injection

Primary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: up to 30 months ]
  2. Complete Remission and Complete Remission with partial hematological recovery (CR/CRh) rate [ Time Frame: up to 23 months ]

Secondary Outcome Measures :
  1. Event-free survival [ Time Frame: up to 49 months ]
  2. Complete remission rate [ Time Frame: up to 36 months ]
  3. Leukemia-free survival [ Time Frame: up to 49 months ]
  4. Duration of remission [ Time Frame: up to 36 months ]
  5. Composite complete remission rate [ Time Frame: up to 36 months ]
    Complete remission (CR) + Complete remission with incomplete hematologic recovery (Cri) + Complete remission with incomplete platelet recovery (CRp)

  6. Transplantation rate [ Time Frame: up to 49 months ]
    Transplantation rate is defined as the percentage of subjects undergoing Hematopoietic stem cell transplant (HSCT) during the study period.

  7. Brief Fatigue Inventory [ Time Frame: up to 36 months ]
    The Brief Fatigue Inventory (BFI) is used to assess the severity of fatigue and the impact of fatigue on daily functioning in patients with fatigue due to cancer and cancer treatment. The BFI short form has 9 items and a 24-hour recall. A global fatigue score is computed by averaging the 9 items.

  8. Complete remission with partial hematological recovery (CRh) rate [ Time Frame: up to 36 months ]
  9. Transfusion conversion rate [ Time Frame: up to 36 months ]
  10. Transfusion maintenance rate [ Time Frame: up to 36 months ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Subject has a diagnosis of primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) according to WHO classification (2008) as determined by pathology review at the treating institute.
  • Subject is refractory to or relapsed after first-line AML therapy (with or without hematopoietic stem cell transplant (HSCT)).

    • Refractory to first-line AML therapy is defined as:

      1. Subject did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A subject eligible for standard therapy must receive at least one cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A subject not eligible for standard therapy must have received at least one complete block of induction therapy seen as the optimum choice of therapy to induce remission for this subject.

    • Untreated first hematologic relapse is defined as:

      1. Subject must have achieved a CR/CRi/CRp (criteria as defined by [Cheson et al, 2003], see Section 5.3) with first line treatment and has hematologic relapse.
  • Subject is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab. A subject with rapidly proliferative disease and unable to wait for the central lab results can be enrolled based on a local test performed after completion of the last interventional treatment. Subjects can be enrolled from a local test result if they have any of the following FLT3 mutations: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD)/D835 or FLT3- TKD/I836.
  • Subject has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
  • Subject is eligible for pre-selected salvage chemotherapy.
  • Subject must meet the following criteria as indicated on the clinical laboratory tests:

    • Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN)
    • Serum total bilirubin ≤ 1.5 x ULN
    • Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
  • Subject is suitable for oral administration of study drug.
  • Female subject must either:

    • Be of non-child bearing potential:

      1. post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
      2. documented as surgically sterile (at least 1 month prior to Screening)
    • Or, if of childbearing potential,

      1. Agree not to try to become pregnant during the study and for 180 days after the final study administration
      2. And have a negative urine pregnancy test at Screening
      3. And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at Screening and throughout the study period and for 180 days after the final study drug administration.
  • Female subject must agree not to breastfeed at Screening and throughout 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 partners who are of childbearing potential must be using highly effective contraception per locally accepted standards in addition to 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 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).
  • Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
  • Subject has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
  • Subject is in second or later hematologic relapse or has received salvage therapy for refractory disease
  • Subject has clinically active central nervous system leukemia.
  • Subject has been diagnosed with another malignancy, unless disease-free for at least 5 years. Subjects with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Subjects with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
  • Subject has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation, and/or maintenance).
  • Subject has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (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.
  • Subjects with mean of triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
  • Subjects with Long QT Syndrome at Screening.
  • Subjects with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal [LLN]).
  • 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 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) 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.
  • Subject has active clinically significant GVHD or is on treatment with systemic corticosteroids for GVHD.
  • Subject has an FLT3 mutation other than the following: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.

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 identifier (NCT number): NCT02421939

  Hide Study Locations
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United States, Alabama
Site US10011
Birmingham, Alabama, United States, 35294-0006
United States, California
Site US10012
Los Angeles, California, United States, 90095-1752
Site US10076
Orange, California, United States, 92868
Site US10073
San Francisco, California, United States, 94143
United States, Connecticut
Site US10067
New Haven, Connecticut, United States, 06504
United States, Florida
Site US10045
Gainesville, Florida, United States, 32610
United States, Georgia
Site US10081
Atlanta, Georgia, United States, 30342
United States, Illinois
Site US10006
Chicago, Illinois, United States, 60637
United States, Kansas
Site US10075
Westwood, Kansas, United States, 66205
United States, Kentucky
Site US10074
Louisville, Kentucky, United States, 40202
United States, Louisiana
Site US10048
New Orleans, Louisiana, United States, 70112
United States, Maryland
Site US10005
Baltimore, Maryland, United States, 21201
United States, Massachusetts
Site US10034
Boston, Massachusetts, United States, 02114
Site US10022
Boston, Massachusetts, United States, 02215
Site US10085
Boston, Massachusetts, United States, 02215
United States, Michigan
Site US10087
Detroit, Michigan, United States, 48201
United States, Minnesota
Site US10057
Minneapolis, Minnesota, United States, 55455
United States, New Hampshire
Site US10023
Lebanon, New Hampshire, United States, 03756-1000
United States, New Jersey
Site US10027
Hackensack, New Jersey, United States, 07601
Site US10077
New Brunswick, New Jersey, United States, 08903
United States, New York
Site US10001
Buffalo, New York, United States, 14263
Site US10037
New York, New York, United States, 10029
Site US10008
New York, New York, United States, 10032
Site US10013
New York, New York, United States, 10065
Site US10072
New York, New York, United States, 10065
Site US10046
Syracuse, New York, United States, 13210
United States, North Carolina
Site US10024
Durham, North Carolina, United States, 27710
Site US10078
Winston-Salem, North Carolina, United States, 27157
United States, Ohio
Site US10044
Cleveland, Ohio, United States, 44106
Site US10084
Columbus, Ohio, United States, 43210
United States, Oklahoma
Site US10058
Oklahoma City, Oklahoma, United States, 73104
United States, Pennsylvania
Site US10041
Hershey, Pennsylvania, United States, 17033
Site US10010
Philadelphia, Pennsylvania, United States, 19104
Site US10080
Philadelphia, Pennsylvania, United States, 19107
United States, South Carolina
Site US10014
Charleston, South Carolina, United States, 29425
United States, Tennessee
Site US10063
Nashville, Tennessee, United States, 37232-0656
United States, Wisconsin
Site US10035
Milwaukee, Wisconsin, United States, 53226
Site BE32002
Yvoir, Belgium, 5530
Canada, Alberta
Site CA15004
Edmonton, Alberta, Canada, T6G 2G3
Canada, Ontario
Site CA15001
Hamilton, Ontario, Canada, L8V 1C3
Site CA15015
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
Site CA15003
Montreal, Quebec, Canada, H1T 2M4
Site FR33013
Brest, France, 29609
Site FR33002
Le Chesnay Cedex, France, 78157
Site FR33010
Lille, France, 59037
Site FR33009
Pessac, France, 33604
Site FR33014
Rennes, France, 35033
Site FR33008
Toulouse, France, 31059
Site DE49009
Dresden, Germany, 01307
Site DE49011
Leipzig, Germany, 04103
Site DE49003
Marburg, Germany, 35043
Site DE49002
Munchen, Germany, 81737
Site DE49010
Tubingen, Germany, 72076
Site IL97201
Ashkelon, Israel, 78278
Site IL97209
Haifa, Israel, 31096
Site IL97203
Jerusalem, Israel, 91031
Site IL97210
Jerusalem, Israel, 91120
Site IL97206
Petah Tikva, Israel, 49100
Site IL97208
Rehovot, Israel, 76100
Site IT39005
Bologna, Italy, 40138
Site IT39010
Brescia, Italy, 25126
Site IT39001
Milan, Italy, 20132
Site IT39004
Palermo, Italy, 90146
Site IT39011
Pavia, Italy, 27100
Site IT39007
Roma, Italy, 00189
Site IT39002
Varese, Italy, 21100
Site JP81002
Nagoya, Aichi, Japan
Site JP81010
Narita, Chiba, Japan
Site JP81026
Yoshida-gun, Fukui, Japan
Site JP81016
Sapporo, Hokkaido, Japan
Site JP81018
Kobe, Hyogo, Japan
Site JP81017
Tsukuba, Ibaraki, Japan
Site JP81009
Isehara, Kanagawa, Japan
Site JP81006
Yokohama, Kanagawa, Japan
Site JP81012
Sendai, Miyagi, Japan
Site JP81007
Kurashiki, Okayama, Japan
Site JP81014
Osakasayama, Osaka, Japan
Site JP81020
Kawagoe, Saitama, Japan
Site JP81027
Shimotsuke, Tochigi, Japan
Site JP81005
Chuo-ku, Tokyo, Japan
Site JP81004
Shinagawa-ku, Tokyo, Japan
Site JP81022
Shinjuku-ku, Tokyo, Japan
Site JP81023
Akita, Japan
Site JP81021
Aomori, Japan
Site JP81013
Kumamoto, Japan
Site JP81025
Kyoto, Japan
Site JP81008
Nagasaki, Japan
Site JP81024
Okayama, Japan
Site JP81011
Osaka, Japan
Korea, Republic of
Site KR82005
Suwon-si, Gyeonggi-do, Korea, Republic of, 443380
Site KR82010
Busan, Korea, Republic of, 602739
Site KR82009
Goyang, Korea, Republic of, 602-715
Site KR82003
Jeollanam-do, Korea, Republic of, 519-809
Site KR82007
Seoul, Korea, Republic of, 110-744
Site KR82004
Seoul, Korea, Republic of, 120-752
Site KR82001
Seoul, Korea, Republic of, 135710
Site KR82002
Seoul, Korea, Republic of, 137701
Site KR82008
Seoul, Korea, Republic of, 138-736
Site KR82011
Seoul, Korea, Republic of, 156-707
Site PL48002
Gdansk, Poland, 80-952
Site PL48005
Opole, Poland, 45-372
Site PL48003
Slupsk, Poland, 76-200
Site PL48004
Wroclaw, Poland, 50-367
Site ES34009
Badalona, Spain, 08025
Site ES34011
Barcelona, Spain, 08035
Site ES34012
Barcelona, Spain, 08036
Site ES34010
Barcelona, Spain, 08916
Site ES34016
Girona, Spain, 17007
Site ES34005
L'Hospitalet de Llobregat, Spain, 08907
Site ES34014
Salamanca, Spain, 37007
Site ES34017
Valencia, Spain, 46026
Site TW88606
Kaohsiung, Taiwan, 112
Site TW88604
Kaohsiung, Taiwan, 83301
Site TW88609
Taichung City, Taiwan, 40705
Site TW88608
Taichung, Taiwan, 404
Site TW88601
Tainan, Taiwan, 704
Site TW88603
Taipei, Taiwan, 10002
Site TW88610
Taipei, Taiwan, 10449
Site TW88611
Taipei, Taiwan, 112
Site TW88602
Taipei, Taiwan, 114
Site TW88605
Taoyuan, Taiwan, 33305
Site TR90001
Ankara, Turkey, 06100
Site TR90004
Ankara, Turkey, 06500
United Kingdom
Site GB44014
Bournemouth, United Kingdom, BH7 7DW
Site GB44013
Harrow, United Kingdom, HA1 3UJ
Site GB44003
Manchester, United Kingdom, M13 9WL
Site GB44015
Plymouth, United Kingdom, PL6 8DH
Sponsors and Collaborators
Astellas Pharma Global Development, Inc.
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Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.

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Responsible Party: Astellas Pharma Global Development, Inc. Identifier: NCT02421939     History of Changes
Other Study ID Numbers: 2215-CL-0301
2015-000140-42 ( EudraCT Number )
First Posted: April 21, 2015    Key Record Dates
Last Update Posted: May 24, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. ):
Relapsed Acute Myeloid Leukemia
FLT3 Mutation
Refractory Acute Myeloid Leukemia
Acute Myeloid Leukemia (AML)

Additional relevant MeSH terms:
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Leukemia, Myeloid
Leukemia, Myeloid, Acute
Neoplasms by Histologic Type
Fludarabine phosphate
Antineoplastic Agents
Antimetabolites, Antineoplastic
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Antiviral Agents
Anti-Infective Agents
Sensory System Agents
Peripheral Nervous System Agents