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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

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ClinicalTrials.gov Identifier: NCT02421939
Recruitment Status : Active, not recruiting
First Posted : April 21, 2015
Last Update Posted : May 24, 2019
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE April 16, 2015
First Posted Date  ICMJE April 21, 2015
Last Update Posted Date May 24, 2019
Actual Study Start Date  ICMJE October 20, 2015
Actual Primary Completion Date September 17, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • Overall Survival (OS) [ Time Frame: up to 30 months ]
  • Complete Remission and Complete Remission with partial hematological recovery (CR/CRh) rate [ Time Frame: up to 23 months ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
Overall Survival (OS) [ Time Frame: up to 56 months ]
Change History Complete list of historical versions of study NCT02421939 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 31, 2017)
  • Event-free survival [ Time Frame: up to 49 months ]
  • Complete remission rate [ Time Frame: up to 36 months ]
  • Leukemia-free survival [ Time Frame: up to 49 months ]
  • Duration of remission [ Time Frame: up to 36 months ]
  • 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)
  • 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.
  • 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.
  • Complete remission with partial hematological recovery (CRh) rate [ Time Frame: up to 36 months ]
  • Transfusion conversion rate [ Time Frame: up to 36 months ]
  • Transfusion maintenance rate [ Time Frame: up to 36 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 16, 2015)
  • Event-free survival [ Time Frame: up to 56 months ]
  • Complete remission [ Time Frame: up to 56 months ]
  • Leukemia-free survival [ Time Frame: up to 56 months ]
  • Duration of remission [ Time Frame: up to 55 months ]
  • Composite complete remission [ Time Frame: up to 55 months ]
    Complete remission (CR) + Complete remission with incomplete hematologic recovery (Cri) + Complete remission with incomplete platelet recovery (CRp)
  • Transplantation rate [ Time Frame: up to 55 months ]
    Transplantation rate is defined as the percentage of subjects undergoing Hematopoietic stem cell transplant (HSCT) during the study period.
  • Brief Fatigue Inventory [ Time Frame: up to 20 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Leukemia, Acute Myeloid (AML)
Intervention  ICMJE
  • Drug: gilteritinib
    tablet, oral
    Other Names:
    • ASP2215
    • XOSPATA®
  • 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
Study Arms  ICMJE
  • Experimental: ASP2215
    Administered once daily
    Intervention: Drug: gilteritinib
  • 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
    Interventions:
    • Drug: LoDAC (Low Dose Cytarabine)
    • Drug: Azacitidine
    • Drug: MEC (Mitoxantrone, Etoposide, Cytarabine)
    • Drug: FLAG-IDA (Granulocyte-Colony Stimulating Factor (G-CSF), Fludarabine, Cytarabine, Idarubicin)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 16, 2018)
371
Original Estimated Enrollment  ICMJE
 (submitted: April 16, 2015)
369
Estimated Study Completion Date  ICMJE December 2020
Actual Primary Completion Date September 17, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belgium,   Canada,   France,   Germany,   Israel,   Italy,   Japan,   Korea, Republic of,   Poland,   Spain,   Taiwan,   Turkey,   United Kingdom,   United States
Removed Location Countries Ireland
 
Administrative Information
NCT Number  ICMJE NCT02421939
Other Study ID Numbers  ICMJE 2215-CL-0301
2015-000140-42 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )
Study Sponsor  ICMJE Astellas Pharma Global Development, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Executive Medical Director Astellas Pharma Global Development, Inc.
PRS Account Astellas Pharma Inc
Verification Date May 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP