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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)

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ClinicalTrials.gov Identifier: NCT03730012
Recruitment Status : Active, not recruiting
First Posted : November 5, 2018
Last Update Posted : June 14, 2021
Sponsor:
Information provided by (Responsible Party):
Astellas Pharma Inc ( Astellas Pharma Global Development, Inc. )

Tracking Information
First Submitted Date  ICMJE November 1, 2018
First Posted Date  ICMJE November 5, 2018
Last Update Posted Date June 14, 2021
Actual Study Start Date  ICMJE June 19, 2019
Actual Primary Completion Date May 14, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 1, 2018)
  • Dose Limiting Toxicities (DLT) - (phase 1) [ Time Frame: Up to 28 days ]
    Incidence of dose limiting toxicities
  • Composite complete remission (CRc) rate (phase 1 and phase 2) [ Time Frame: Up to 56 days (2 cycles of treatment) ]
    Number of participants with CRc. CRc is defined as a complete remission (CR), complete remission without platelet recovery (CRp) or complete remission with incomplete hematologic recovery (CRi). CRc rate is defined as the rate of all complete and incomplete remission (i.e., CR + CRp + CRi).
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 4, 2019)
  • PK of Gilteritinib in plasma: (Ctrough) [ Time Frame: Up to 6 months ]
    Ctrough will be derived from pharmacokinetic (PK) plasma samples collected.
  • Complete Remission (CR) rate [ Time Frame: Up to 3 years ]
    Number of participants with complete remission (CR)
  • Best Response rate (CRc + partial remission [PR]) [ Time Frame: Up to 3 years ]
    Best response is defined as the best-measured response (CR, CRp, CRi or PR) post-treatment.
  • Duration of remission [ Time Frame: Up to 3 years ]
    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).
  • Event Free Survival (EFS) [ Time Frame: Up to 3 years ]
    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.
  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
    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.
  • Complete Remission (CR) rate with partial hematologic recovery (CRh) [ Time Frame: Up to 3 years ]
    Number of participants with complete remission (CR) with partial hematologic recovery (CRh)
  • Safety assessed by Adverse Events [ Time Frame: Up to 3 years ]
    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.
  • Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 3 years ]
    Number of participants with potentially clinically significant laboratory values
  • Number of participants with vital sign abnormalities and/or adverse events (AEs) [ Time Frame: Up to 3 years ]
    Number of participants with potentially clinically significant vital sign values.
  • Safety assessed by 12-lead electrocardiogram (ECG) [ Time Frame: Up to 3 years ]
    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.
  • Safety assessed by Eastern Cooperative Oncology Group (ECOG) performance score [ Time Frame: Up to 3 years ]
    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.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 1, 2018)
  • PK of Gilteritinib in plasma: (Ctrough) [ Time Frame: Up to 6 months ]
    Ctrough will be derived from pharmacokinetic (PK) plasma samples collected.
  • Complete Remission (CR) rate [ Time Frame: Up to 3 years ]
    Number of participants with complete remission (CR)
  • Best Response rate (CRc + partial remission [PR]) [ Time Frame: Up to 3 years ]
    Best response is defined as the best-measured response (CR, CRp, CRi or PR) post-treatment.
  • Duration of remission [ Time Frame: Up to 3 years ]
    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).
  • Event Free Survival (EFS) [ Time Frame: Up to 3 years ]
    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.
  • Overall Survival (OS) [ Time Frame: Up to 3 years ]
    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.
  • Safety assessed by Adverse Events [ Time Frame: Up to 3 years ]
    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.
  • Number of participants with laboratory value abnormalities and/or adverse events (AEs) [ Time Frame: Up to 3 years ]
    Number of participants with potentially clinically significant laboratory values
  • Number of participants with vital sign abnormalities and/or adverse events (AEs) [ Time Frame: Up to 3 years ]
    Number of participants with potentially clinically significant vital sign values.
  • Safety assessed by 12-lead electrocardiogram (ECG) [ Time Frame: Up to 3 years ]
    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.
  • Safety assessed by Eastern Cooperative Oncology Group (ECOG) performance score [ Time Frame: Up to 3 years ]
    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.
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 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FMS-like Tyrosine Kinase (FLT3) Mutated Acute Myeloid Leukemia (AML)
Official Title  ICMJE Phase 1/2 Study of ASP2215 (Gilteritinib) Combined With Atezolizumab in Patients With Relapsed or Treatment Refractory FLT3 Mutated Acute Myeloid Leukemia (AML)
Brief Summary

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Acute Myeloid Leukemia (AML)
  • Acute Myeloid Leukemia With FMS-like Tyrosine Kinase (FLT3) Mutation
Intervention  ICMJE
  • Drug: gilteritinib
    Gilteritinib is administered orally
    Other Name: ASP2215
  • Drug: atezolizumab
    Atezolizumab is administered by intravenous infusion
Study Arms  ICMJE Experimental: Gilteritinib plus Atezolizumab
Participants 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.
Interventions:
  • Drug: gilteritinib
  • Drug: atezolizumab
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: April 8, 2021)
12
Original Estimated Enrollment  ICMJE
 (submitted: November 1, 2018)
61
Estimated Study Completion Date  ICMJE June 30, 2021
Actual Primary Completion Date May 14, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 (will only apply to subjects enrolled in the phase 2 portion of the study).
  • 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.
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03730012
Other Study ID Numbers  ICMJE 2215-CL-1101
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: Access to anonymized individual participant level data will not be provided for this trial as it meets one or more of the exceptions described on www.clinicalstudydatarequest.com under "Sponsor Specific Details for Astellas."
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
PRS Account Astellas Pharma Inc
Verification Date June 2021

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