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A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)

NCT03730012

Description:

The purpose of this study is to determine the safety and tolerability of gilteritinib given in combination with atezolizumab in participants with relapsed or treatment refractory FMS-like tyrosine kinase 3 (FLT3) mutated AML and to determine the composite complete remission (CRc) rate for participants who either discontinued the study or completed 2 cycles of gilteritinib given in combination with atezolizumab. This study will also evaluate pharmacokinetics (PK), response to treatment, remission and survival. Adverse events (AEs), clinical laboratory results, vital signs, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance status scores will also be assessed.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: A Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)
  • Official Title: Phase 1/2 Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FLT3 Mutated Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: 2215-CL-1101
  • NCT ID: NCT03730012

Conditions

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

Interventions

DrugSynonymsArms
gilteritinibASP2215Gilteritinib plus Atezolizumab
atezolizumabGilteritinib plus Atezolizumab

Purpose

The purpose of this study is to determine the safety and tolerability of gilteritinib given in combination with atezolizumab in participants with relapsed or treatment refractory FMS-like tyrosine kinase 3 (FLT3) mutated AML and to determine the composite complete remission (CRc) rate for participants who either discontinued the study or completed 2 cycles of gilteritinib given in combination with atezolizumab. This study will also evaluate pharmacokinetics (PK), response to treatment, remission and survival. Adverse events (AEs), clinical laboratory results, vital signs, electrocardiograms (ECGs), and Eastern Cooperative Oncology Group (ECOG) performance status scores will also be assessed.

Detailed Description

      This study will have 2 phases.

      Phase 1:

      The phase 1 portion of this study is to establish the recommended phase 2 dose (RP2D) of
      gilteritinib given in combination with atezolizumab.

      Phase 2:

      The phase 2 portion of the study will treat patients with gilteritinib and atezolizumab at
      the RP2D and will enroll in two stages. The first stage will evaluate the remission rate and
      if a minimum rate is achieved, a second stage of enrollment will continue.
    

Trial Arms

NameTypeDescriptionInterventions
Gilteritinib plus AtezolizumabExperimentalParticipants will be treated with gilteritinib once daily for the phase 1 portion of the study to establish the recommended dose for the phase 2 portion. In the phase 2 portion, the participants will be treated with gilteritinib once daily at dose determined by the phase 1 portion of the study. Atezolizumab will be administered once every 2 weeks for the phase 1 and 2 portions of the study. Participants will be treated on continuous cycles until they no longer derive clinical benefit in the judgment of the treating physician, have unacceptable toxicity, undergo hematopoietic stem cell transplantation (HSCT), or meet 1 of the discontinuation criteria; whichever occurs first.
  • gilteritinib
  • atezolizumab

Eligibility Criteria

        Inclusion Criteria:

          -  Subject is considered an adult according to local regulation at the time of signing
             informed consent form (ICF).

          -  Subject has defined AML by the World Health Organization (WHO) criteria (2017) and
             fulfills one of the following:

               -  Refractory to at least 1 cycle of induction chemotherapy

               -  Relapsed after achieving remission with a prior therapy

          -  Subject is positive for FLT3 mutation in bone marrow or blood after completion of the
             subject's last interventional treatment.

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

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

               -  Serum Aspartate aminotransferase (AST) and Alanine Aminotransferease (ALT) ≤ 2.5
                  x upper limit of normal (ULN)

               -  Serum total bilirubin (TBL) ≤ 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.

          -  A female subject is eligible to participate if she is not pregnant and at least one of
             the following conditions applies:

               -  Not a woman of childbearing potential (WOCBP) OR

               -  WOCBP who agrees to follow the contraceptive guidance throughout the treatment
                  period and for at least 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 at least 180 days after the final study drug administration.

          -  Female subject must not donate ova starting at screening and throughout the study
             period, and for at least 180 days after the final study drug administration.

          -  A male subject must not donate sperm starting at screening and throughout the
             treatment period, and for at least 120 days after the final study drug administration.

          -  A male subject with female partner(s) of child-bearing potential must agree to use
             contraception during the treatment period, and for at least 120 days after the final
             study drug administration.

          -  Male subject with a pregnant or breastfeeding partner(s) must agree to remain
             abstinent or use a condom for the duration of the pregnancy or time partner is
             breastfeeding throughout the treatment period, and for 120 days after the final study
             drug administration.

          -  Subject agrees not to participate in another investigational study while on treatment.

        Exclusion Criteria:

          -  Subject was diagnosed as acute promyelocytic leukemia.

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

          -  Subject has AML secondary to prior chemotherapy for other neoplasms (except for
             myelodysplastic syndrome).

          -  Subject has clinically active central nervous system leukemia.

          -  Subject has uncontrolled or significant cardiovascular disease, including:

               -  A myocardial infarction within 12 months

               -  Uncontrolled angina within 6 months

               -  History of clinically significant ventricular arrhythmias (such as ventricular
                  tachycardia, ventricular fibrillation, torsades de pointes) or any history of
                  arrhythmia

               -  Uncontrolled hypertension

          -  Subject has baseline left ventricular ejection fraction that is ≥ 45%.

          -  Subject has mean triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at
             Screening based on central reading.

          -  Subject has congenital or acquired Long QT Syndrome at screening.

          -  Subject has hypokalemia and/or hypomagnesemia at screening.

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

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

          -  Subject is receiving or plans to receive concomitant chemotherapy or immunotherapy.

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

          -  Subject with systemic fungal, bacterial, viral or other uncontrolled infection that is
             exhibiting ongoing signs/symptoms related to the infection without improvement despite
             appropriate antibiotics or other treatment. Subject needs to be off pressors and have
             negative blood cultures for 48 hours.

          -  Subject has not recovered from any prior therapy related toxicities.

          -  Subject is known to have human immunodeficiency virus infection.

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

          -  Subject has previously been treated with gilteritinib, quizartinib or crenolanib.

          -  Subject has active clinically significant graft-versus-host disease (GVHD) or is on
             treatment with systemic corticosteroids for GVHD.

          -  Subject has relapsed after allogeneic hematopoietic stem cell transplant (HCST).

          -  Subject has an active autoimmune disorder that makes the subject unsuitable for study
             treatment or participation.

          -  Subject has any condition that makes the subject unsuitable for study participation.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Dose Limiting Toxicities (DLT) - (phase 1)
Time Frame:Up to 28 days
Safety Issue:
Description:Incidence of dose limiting toxicities

Secondary Outcome Measures

Measure:PK of Gilteritinib in plasma: (Ctrough)
Time Frame:Up to 6 months
Safety Issue:
Description:Ctrough will be derived from pharmacokinetic (PK) plasma samples collected.
Measure:Complete Remission (CR) rate
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants with complete remission (CR)
Measure:Best Response rate (CRc + partial remission [PR])
Time Frame:Up to 3 years
Safety Issue:
Description:Best response is defined as the best-measured response (CR, CRp, CRi or PR) post-treatment.
Measure:Duration of remission
Time Frame:Up to 3 years
Safety Issue:
Description:Duration of remission is defined as time from date of first CRc, CR, CRi, CRp, and response (CRc + PR) until the date of documented relapse. Duration of remission includes duration of CRc, CR, CRi, CRp and response (CRc + PR).
Measure:Event Free Survival (EFS)
Time Frame:Up to 3 years
Safety Issue:
Description:EFS is defined as the time from the date of enrollment until the date of documented relapse from CR, CRp or CRi, treatment failure or death from any cause, whichever occurs first.
Measure:Overall Survival (OS)
Time Frame:Up to 3 years
Safety Issue:
Description:OS is defined as the time from the date of enrollment until the date of death from any cause. For a subject who is not known to have died by the end-of-study follow-up, OS is censored at the date of last contact.
Measure:Complete Remission (CR) rate with partial hematologic recovery (CRh)
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants with complete remission (CR) with partial hematologic recovery (CRh)
Measure:Safety assessed by Adverse Events
Time Frame:Up to 3 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a participant administered a study drug, and which does not necessarily have to have a causal relationship with this treatment.
Measure:Number of participants with laboratory value abnormalities and/or adverse events (AEs)
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants with potentially clinically significant laboratory values
Measure:Number of participants with vital sign abnormalities and/or adverse events (AEs)
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants with potentially clinically significant vital sign values.
Measure:Safety assessed by 12-lead electrocardiogram (ECG)
Time Frame:Up to 3 years
Safety Issue:
Description:12-lead ECGs will be recorded in triplicate (3 separate ECGs, 10 minutes resting prior to first ECG and at least 5 minutes apart per time point) 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:Safety assessed by Eastern Cooperative Oncology Group (ECOG) performance score
Time Frame:Up to 3 years
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 1/Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Astellas Pharma Global Development, Inc.

Trial Keywords

  • AML
  • gilteritinib
  • ASP2215
  • Acute Myeloid Leukemia
  • FLT3

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