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A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy

NCT02752035

Description:

This is a clinical study for adult patients who have recently been diagnosed with acute myeloid leukemia or AML. AML is a type of cancer. It is when bone marrow makes white blood cells that are not normal. These are called leukemia cells. Some patients with AML have a mutation, or change, in the FLT3 gene. This gene helps leukemia cells make a protein called FLT3. This protein causes the leukemia cells to grow faster. For patients with AML who cannot receive standard chemotherapy, azacitidine (also known as Vidaza®) is a current standard of care treatment option in the United States. This clinical study is testing an experimental medicine called ASP2215, also known as gilteritinib. Gilteritinib works by stopping the leukemia cells from making the FLT3 protein. This can help stop the leukemia cells from growing faster. This study will compare two different treatments. Patients are assigned to one of these two groups by chance: a medicine called azacitidine, also known as Vidaza®, or an experimental medicine gilteritinib in combination with azacitidine. There is a twice as much chance to receive both medicines combined than azacitidine alone. The clinical study may help show which treatment helps patients live longer.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of ASP2215 (Gilteritinib) by Itself, ASP2215 Combined With Azacitidine or Azacitidine by Itself to Treat Adult Patients Who Have Recently Been Diagnosed With Acute Myeloid Leukemia With a FLT3 Gene Mutation and Who Cannot Receive Standard Chemotherapy
  • Official Title: A Phase 2/3 Multicenter, Open-label, 3-arm, 2-Stage Randomized Study of ASP2215 (Gilteritinib), Combination of ASP2215 Plus Azacitidine and Azacitidine Alone in the Treatment of Newly Diagnosed Acute Myeloid Leukemia With FLT3 Mutation in Patients Not Eligible for Intensive Induction Chemotherapy

Clinical Trial IDs

  • ORG STUDY ID: 2215-CL-0201
  • SECONDARY ID: 2015-001790-41
  • NCT ID: NCT02752035

Conditions

  • Acute Myeloid Leukemia (AML)
  • Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation

Interventions

DrugSynonymsArms
gilteritinibASP2215Arm AC: ASP2215 + azacitidine
azacitidineArm AC: ASP2215 + azacitidine

Purpose

This is a clinical study for adult patients who have recently been diagnosed with acute myeloid leukemia or AML. AML is a type of cancer. It is when bone marrow makes white blood cells that are not normal. These are called leukemia cells. Some patients with AML have a mutation, or change, in the FLT3 gene. This gene helps leukemia cells make a protein called FLT3. This protein causes the leukemia cells to grow faster. For patients with AML who cannot receive standard chemotherapy, azacitidine (also known as Vidaza®) is a current standard of care treatment option in the United States. This clinical study is testing an experimental medicine called ASP2215, also known as gilteritinib. Gilteritinib works by stopping the leukemia cells from making the FLT3 protein. This can help stop the leukemia cells from growing faster. This study will compare three different treatments. Patients are assigned to one of these three groups by chance: an experimental medicine gilteritinib, a different medicine called azacitidine, also known as Vidaza®, or both medicines (azacitidine and gilteritinib) together. The clinical study may help show which treatment helps patients live longer.

Detailed Description

      Subjects considered an adult according to local regulation at the time of obtaining informed
      consent may participate in the study.

      Safety Cohort Prior to initiation of the randomized trial, 8 to 12 subjects will be enrolled
      to evaluate the safety and tolerability of ASP2215 given with azacitidine therapy in the
      study population.

      Randomized Trial Approximately 528 subjects will be randomized in a 1:1:1 ratio to receive
      ASP2215 (Arm A), ASP2215 plus azacitidine (Arm AC) or azacitidine only (Arm C).

      Subjects will enter the screening period up to 14 days prior to the start of treatment.
      Subjects will be administered treatment over 28-day cycles.
    

Trial Arms

NameTypeDescriptionInterventions
Dose escalation of ASP2215 given with azacitidineExperimentalSubjects will be treated with ASP2215 daily (days 1-28) and azacitidine daily for 7 days (days 1-7).
  • gilteritinib
  • azacitidine
Arm A: ASP2215ExperimentalSubjects will be treated daily each 28-day cycle.
  • gilteritinib
Arm AC: ASP2215 + azacitidineExperimentalSubjects will be treated with ASP2215 daily and azacitidine daily for 7 days (days 1-7) each 28-day cycle.
  • gilteritinib
  • azacitidine
Arm C: azacitidineActive ComparatorSubjects will be treated with azacitidine for 7 days (days 1-7) each 28-day cycle.
  • azacitidine

Eligibility Criteria

        Inclusion Criteria:

          -  Subject is considered an adult according to local regulation at the time of obtaining
             informed consent.

          -  Subject has a diagnosis of previously-untreated AML according to World Health
             Organization (WHO) classification [Swerdlow et al, 2008] as determined by pathology
             review at the treating institution.

          -  Subject is positive for FLT3 mutation (internal tandem duplication [ITD] or tyrosine
             kinase domain [TKD] [D835/I836] mutation) in bone marrow or whole blood as determined
             by central laboratory. Note: Only applicable to the randomization portion.

          -  Subject is ineligible for intensive induction chemotherapy by meeting at least 1 of
             the following criteria:

               1. Subject is ≥ 75 years of age.

               2. Subject has any of the following comorbidities:

                    -  Congestive heart failure (New York Heart Association {NYHA} class ≤ 3) or
                       ejection fraction (Ef) ≤ 50%;

                    -  Creatinine > 2 mg/dL (177 µmol/L), dialysis or prior renal transplant;

                    -  ECOG performance status ≥ 3;

                    -  Prior or current malignancy that does not require concurrent treatment;

                    -  Subject has received a cumulative anthracycline dose above 400 mg/m2 of
                       doxorubicin (or cumulative maximum dose of another anthracycline).

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

               -  Serum AST and ALT ≤ 2.5 x Institutional upper limit of normal (ULN)

               -  Serum total bilirubin ≤ 1.5 x Institutional ULN

               -  Serum potassium ≥ Institutional lower limit of normal (LLN)

               -  Serum magnesium ≥ Institutional LLN

          -  Subject is suitable for oral administration of study drug.

          -  Female subject must either:

               -  Be of nonchildbearing potential:

                    -  Postmenopausal (defined as at least 1 year without any menses) prior to
                       screening, or

                    -  Documented surgically sterile or status posthysterectomy (at least 1 month
                       prior to screening)

               -  Or, if of childbearing potential,

                    -  Agree not to try to become pregnant during the study and for 180 days after
                       the final study drug administration

                    -  And have a negative urine or serum pregnancy test at screening

                    -  And, if heterosexually active, agree to consistently use 2 forms of
                       effective contraception per locally accepted standards, 1 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.

          -  Female subject must agree not to breastfeed starting 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
             2 forms of effective contraception per locally accepted standards, 1 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).

          -  Subject has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).

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

               -  Emergency leukapheresis

               -  Hydroxyurea for ≤ 14 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,
                  nausea/vomiting or pain

          -  Subject has clinically active central nervous system leukemia.

          -  Subject has been diagnosed with another malignancy that requires concurrent treatment
             or hepatic malignancy regardless of need for treatment.

          -  Subject has clinically significant coagulation abnormality unless secondary to AML.

          -  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 requires treatment with concomitant drugs that are strong inducers of
             cytochrome P450 CYP3A.

          -  Subject requires treatment with concomitant drugs that are strong inhibitors or
             inducers of 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 or sigma nonspecific receptor with the exception of drugs that are considered
             absolutely essential for the care of the subject.

          -  Subject has congestive heart failure classified as New York Heart Association Class
             IV.

          -  Subject with mean Fridericia-corrected QT interval (QTcF) > 450 ms at screening based
             on central reading.

          -  Subject with a history of Long QT Syndrome at screening.

          -  Subject has known pulmonary disease with diffusion capacity of lung for carbon
             monoxide (DLCO) ≤ 65%, forced expiratory volume in the first second (FEV1) ≤ 65%,
             dyspnea at rest or requiring oxygen or any pleural neoplasm (Transient use of
             supplemental oxygen is allowed.)

          -  Subject has an active uncontrolled infection. If an infection is present, the patient
             must be receiving definitive therapy and have no signs of progressing infection.
             Progressing infection is defined as hemodynamic instability attributable to sepsis or
             new symptoms, worsening physical signs or radiographic findings attributable to
             infection. Persisting fever without other signs or symptoms will not be interpreted as
             progressing 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,
             including any contraindications of azacitidine.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall survival (OS)
Time Frame:Up to 36 months
Safety Issue:
Description:OS is defined as the time from the date of randomization until the date of death from any cause.

Secondary Outcome Measures

Measure:Event free survival (EFS)
Time Frame:Up to 36 months
Safety Issue:
Description:EFS is defined as the time from the date of randomization until the date of documented relapse from complete remission (CR), complete remission with incomplete platelet recovery (CRp) or complete remission with incomplete hematologic recovery (Cri), treatment failure or death from any cause, whichever occurs first.
Measure:Best response
Time Frame:Up to 36 months
Safety Issue:
Description:Best response is defined as the best measured response (CR, CRp, Cri or treatment failure) posttreatment
Measure:Leukemia free survival (LFS)
Time Frame:Up to 36 months
Safety Issue:
Description:LFS is defined as the time from the date of first composite complete remission (CRc) until the date of documented relapse or death for subjects who achieve CRc.
Measure:Duration of remission
Time Frame:Up to 36 months
Safety Issue:
Description:Duration of remission includes duration of CRc, CR, Cri, CRp and response (CRc + partial response [PR]). Duration of CRc is defined as the time from the date of first CRc until the date of documented relapse for subjects who achieve CRc. Duration of remission is similarly defined for CR, Cri and CRp.
Measure:Participant reported fatigue from Brief Fatigue Inventory (BFI)
Time Frame:Up to 36 months
Safety Issue:
Description:The BFI was developed to assess the severity of fatigue and the impact of fatigue on daily functioning in subjects with fatigue due to cancer and cancer treatment The BFI inventory has 9 items and a 24-hour recall. A global fatigue score is computed by averaging the 9 items.
Measure:Safety assessed by adverse events (AEs)
Time Frame:Up to 41 months
Safety Issue:
Description:
Measure:Number of participants with abnormal laboratory values and/or adverse events related to treatment
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Number of participants with abnormal vital signs and/or adverse events related to treatment
Time Frame:Up to 36 months
Safety Issue:
Description:
Measure:Safety assessed by electrocardiograms (ECGs)
Time Frame:Up to 36 months
Safety Issue:
Description:The 12-lead ECGs will be recorded in triplicate (3 separate ECGs) and transmitted electronically for central reading. The mean of the triplicate ECG from central read will be used for all final treatment decisions and adverse event reporting.
Measure:Eastern Cooperative Oncology Group (ECOG) performance status score
Time Frame:Up to 36 months
Safety Issue:
Description:ECOG performance status measured on 6 point scale to assess participant's performance status. 0=Fully active, able to carry on all pre-disease activities without restriction; 1=Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature; 2= Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about more than 50% of waking hours; 3=Capable of only limited self-care, confined to bed or chair more than 50% of waking hours; 4=Completely disabled. Cannot carry on any self-care. Totally confined to bed or chair; 5=Dead. 0=Best status; 5=Worst status.

Details

Phase:Phase 2/Phase 3
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • AML
  • ASP2215
  • Newly Diagnosed AML
  • gilteritinib
  • Acute Myeloid Leukemia (AML)
  • FLT3

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