Quizartinib or Placebo Plus Chemotherapy in Newly Diagnosed Patients With FLT3-ITD Negative AML (QuANTUM-WILD)

Daiichi Sankyo

Status and phase: Enrolling; Phase 3

Conditions: Leukemia

Treatments: Drug: Quizartinib; Drug: Placebo; Drug: Chemotherapy

Study type: Interventional

Funder types: Industry

Identifiers

NCT06578247

2023-507936-20-00 (EU Trial (CTIS) Number)

AC220-168

Details and patient eligibility

About

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).

Full 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.

Enrollment: 700 estimated patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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700 participants in 3 patient groups, including a placebo group

Arm A: Quizartinib + Chemotherapy

Experimental group

Description:

Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive quizartinib at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)

Treatment:

Drug: Chemotherapy

Drug: Quizartinib

Arm B: Placebo + Chemotherapy

Placebo Comparator group

Description:

Participants will receive placebo at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)

Treatment:

Drug: Chemotherapy

Drug: Placebo

Arm C: Quizartinib + Chemotherapy then Placebo Maintenance

Experimental group

Description:

Participants will receive quizartinib at 60 mg/day orally once daily for 14 days starting after the completion of chemotherapy in Induction and Consolidation Phase. In the Maintenance Phase, participants will receive placebo at 60 mg/day orally once daily for up to 36 cycles (28-day cycle)

Treatment:

Drug: Chemotherapy

Drug: Placebo

Drug: Quizartinib