Leukemia
Conditions
Keywords
acute myeloid leukemia, quizartinib, FLT3, FLT3-ITD, Chemotherapy, FLT3-WT
Brief summary
This study will compare the effects of Quizartinib versus placebo in combination with chemotherapy in participants with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML).
Detailed description
This is a clinical trial to compare the effect of quizartinib versus placebo (administered with standard induction and consolidation chemotherapy, then administered as maintenance therapy for up to 36 cycles) on the primary endpoint of overall survival (OS) in adult patients with newly diagnosed FMS-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) negative acute myeloid leukemia (AML). Participants will be tested for FLT3-ITD mutation status in a central laboratory using a validated assay.
Interventions
DRUGQuizartinib
Participants will receive quizartinib at 60 mg/day orally once daily
DRUGPlacebo
Participants will receive placebo at 60 mg/day orally once daily
DRUGChemotherapy
Participants will receive commercially available cytarabine (cytosine arabinoside) and anthracycline (daunorubicin or idarubicin).
Sponsors
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Masking description
This study has a double-blind design. Neither the participants nor any of the investigators, Sponsor, Independent Review Committee (IRC) or contract research organizations (CROs) will be aware of the treatments received. An independent biostatistician, not otherwise part of the Sponsor trial team, will generate the randomization schedule.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Key Inclusion Criteria: 1. Must be competent and able to comprehend, sign, and date an Ethics Committee (EC)- or Institutional Review Board (IRB)-approved ICF before performance of any trial-specific procedures or tests. 2. ≥18 years or the minimum legal adult age (whichever is greater) and ≤70 years (at Screening). 3. Newly diagnosed, morphologically documented primary AML based on the World Health Organization (WHO) 2016 classification (at Screening) 4. Eastern Cooperative Oncology Group (ECOG) performance status (at the time the participant signs their ICF) of 0-2. 5. Participant is a candidate for standard "7+3" induction chemotherapy regimen as specified in the protocol per investigator assessment Key
Exclusion criteria
1. Diagnosis of acute promyelocytic leukemia (APL), French-American-British classification M3 or WHO classification of APL with translocation, t(15;17)(q22;q12), or BCR-ABL positive leukemia (ie, chronic myelogenous leukemia in blast crisis); participants who undergo diagnostic workup for APL and treatment with all-trans retinoic acid (ATRA), but who are found not to have APL, are eligible (treatment with ATRA must be discontinued before starting induction chemotherapy). 2. Diagnosis of AML secondary to prior chemotherapy or radiotherapy. 3. Diagnosis of AML with known antecedent myelodysplastic syndrome (MDS) or a myeloproliferative neoplasm (MPN) or MDS/MPNs including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (aCML), juvenile myelomonocytic leukemia (JMML) and others. 4. Participants with newly diagnosed AML with FLT3-ITD mutations (FLT3-ITD \[+\]) present at ≥5% VAF (or ≥0.05 SR) based on a validated FLT3 mutation assay. 5. Prior treatment for AML, except for the following allowances prior to Day 1 of chemotherapy: 1. Leukapheresis; 2. Treatment for hyperleukocytosis with hydroxyurea; 3. Cranial radiotherapy for central nervous system (CNS) leukostasis; 4. Prophylactic intrathecal chemotherapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (Arm A vs Arm B) | Date of first patient randomized to the target number of deaths reached, up to approximately 42 months | Overall survival (OS) is defined as the time from randomization until death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Event-free survival (Arm A vs. Arm B) | Date of randomization up to approximately 42 months | Event-free survival (EFS) is defined as time from randomization to date of failure to achieve CR at end of induction, relapse after CR, or death due to any cause, whichever occurs first |
| Duration of complete response (Arm A vs. Arm B) | Date of randomization up to approximately 42 months | Duration of complete response (DoCR) is defined as time from the first documented CR until documented relapse or death due to any cause, whichever comes first. As assessed by Independent Review Committee. |
| Relapse-free survival (Arm A vs. Arm B) | Date of randomization up to approximately 42 months | Relapse-free survival (RFS) is defined as time from randomization, for participants who achieve CR in the Induction Phase, until relapse or death due to any cause, whichever comes first. As assessed by Independent Review Committee . |
| Complete remission rate (Arm A vs. Arm B) | At end of Induction Phase, up to approximately 120 days | Complete remission rate (CR) is defined as proportion of of participants who achieved a CR. As assessed by Independent Review Committee. |
| Complete remission rate with minimal or measurable residual disease (Arm A vs. Arm B) | At end of Induction Phase (Cycle 2 or Cycles 1 and 2), up to approximately 120 days | Proportion of participants achieving CR with minimal or measurable residual disease (MRD) negativity. As assessed by Independent Review Committee. |
| Number of Participants With Treatment-emergent Adverse Events (Arm A vs. Arm B) | Date of first dose up to 30 days after last dose, up to approximately 42 months | Treatment-emergent adverse events (TEAE) are defined as those AEs with start or worsening date during the on-treatment period (from the first dose date of quizartinib/placebo to 30 days after the last dose date of quizartinib/placebo). |
Countries
Australia, Austria, Belgium, Brazil, Bulgaria, Canada, China, Croatia, Czechia, France, Germany, Hong Kong, Hungary, Italy, Japan, Norway, Poland, Portugal, Romania, Serbia, Singapore, South Korea, Spain, Sweden, Switzerland, Taiwan, United Kingdom, United States
Contacts
STUDY_DIRECTORGlobal Clinical Leader
Daiichi Sankyo
Outcome results
None listed