Quizartinib maintenance at two doses for FLT3‑ITD positive AML in first complete remission

A Phase 2, Multicenter, Randomized, Open-label Trial to Evaluate Safety and Efficacy of Two Dose Levels of Quizartinib as Maintenance for Adult Patients With Newly Diagnosed FLT3-ITD (+) Acute Myeloid Leukemia in Complete Remission

This trial tests whether two different doses of quizartinib can help prevent relapse in adults with FLT3‑ITD positive AML who are in first complete remission and have not had an allogeneic stem cell transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 130 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Daiichi Sankyo (industry)
• Drugs / interventions: chemotherapy, quizartinib
• Locations: 58 sites (Baltimore, Maryland and 57 other locations)
• Trial ID: NCT06824168 on ClinicalTrials.gov

What this trial studies

This Phase 2, two‑arm interventional trial randomizes adults with newly diagnosed FLT3‑ITD positive AML who are in first complete remission and have not received allo‑HSCT to receive either a higher or lower oral dose of quizartinib as maintenance therapy after induction/consolidation. Participants will have scheduled clinic visits, blood and marrow monitoring, and cardiac surveillance including a Holter sub‑study to evaluate the effect of rapid heart rate acceleration on cardiac safety. Primary outcomes emphasize relapse rates and safety/tolerability during maintenance, with secondary endpoints including survival measures and cardiac events. Local molecular testing confirms FLT3‑ITD status and eligibility requires a recent bone marrow result showing <5% blasts prior to starting maintenance.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed FLT3‑ITD positive AML in first complete remission after induction/consolidation who have not had allo‑HSCT and meet organ function and monitoring requirements.

Not a fit: Patients who already received an allogeneic stem cell transplant, who are FLT3‑negative or have other non‑targetable mutations, or who have active uncontrolled disease or significant cardiac issues may not receive benefit from this maintenance approach.

Why it matters

Potential benefit: If successful, maintenance quizartinib could lengthen remissions and lower relapse risk for FLT3‑ITD positive AML patients who do not undergo transplant.

How similar studies have performed: Other FLT3 inhibitors have improved outcomes in FLT3‑ITD AML and quizartinib showed activity in prior trials, but use of quizartinib specifically as post‑remission maintenance without transplant remains under active study.

Eligibility criteria

Key Inclusion Criteria:

1. Adults ≥18 years of age or the minimum legal adult age (whichever is greater) on the day of signing the ICF (no upper limit of age).
2. Newly diagnosed, morphologically documented primary AML or AML secondary to myelodysplastic syndrome or a myeloproliferative neoplasm based on the World Health Organization (WHO) 2008/2016 classification.
3. Participant has confirmed FLT3-ITD-positive (≥0.05 SR or ≥5% VAF) activating mutation from initial diagnosis in bone marrow or peripheral blood as determined by a local institution's validated molecular testing.
4. Participants must have confirmed, morphologically documented CR1, on the most recent BMA, based on the local laboratory results, performed within 28 days prior to C1D1 of maintenance therapy. Complete remission will be defined as \<5% blasts in the bone marrow with no morphologic characteristics of acute leukemia (e.g., Auer Rods), no evidence of extramedullary disease, and no leukemic blasts in the peripheral blood.

   Complete blood count recovery is required with absolute neutrophil count of more than 1.000 × 109/L and platelets more than 100 × 109/L (IWG criteria).27
5. Participant must meet the following prior therapy requirements:

   1. Has received at least one cycle of induction therapy but no more than two to achieve CR1. The induction cycles can be the same regimen or different regimens and may contain conventional agents only (e.g., cytarabine + daunorubicin or idarubicin: "7 + 3" or "5 + 2"), or a combination with FLT3 inhibitors.
   2. Has not received more than four cycles of consolidation therapy. Regimens may contain conventional agents only.
   3. FLT3 inhibitors are permitted as part of the induction or consolidation treatment.

   Participants who received FLT3 inhibitors before enrollment in the trial will need a washout period of 14 days.
6. Able to begin the maintenance phase within 60 days of D1 of the last consolidation cycle received.
7. Eastern Cooperative Oncology Group (ECOG) PS of 0 to 2.

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 (i.e., 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 for other neoplasms.
3. Prior treatment for AML, except for the following allowances:

   1. Induction and consolidation therapy, as previously described (inclusion criterion #5)
   2. Leukapheresis
   3. Hydroxyurea to treat hyperleukocytosis
   4. Cranial radiotherapy for central nervous system (CNS) leukostasis
   5. Prophylactic intrathecal chemotherapy
   6. Growth factor/cytokine support
4. Participant had received allo-HSCT as part of AML treatment.
5. Treatment with any strong or moderate CYP3A inducers within 2 weeks or 5 half-lives of randomization whichever is longer
6. Uncontrolled or significant cardiovascular disease, including the following:

   1. QTcF interval \>450 ms (based on average of triplicate ECG at Screening)
   2. Diagnosed or suspected congenital long QT syndrome or known family history of congenital long QT syndrome
   3. History of clinically relevant ventricular arrhythmias, such as ventricular tachycardia, ventricular fibrillation, or Torsade de Pointes
   4. Participant has bradycardia of less than 50 beats per minute (bpm; as determined by central reading), unless the participant has a pacemaker
   5. History of second- or third-degree heart block. Candidates with a history of heart block may be eligible if they currently have pacemakers and have no history of fainting or clinically relevant arrhythmia with pacemakers.
   6. Myocardial infarction within 6 months prior to screening
   7. Uncontrolled angina pectoris within 6 months prior to screening
   8. New York Heart Association Class 3 or 4 congestive heart failure
   9. LVEF ≤45% or institutional lower limit of normal
   10. Uncontrolled hypertension (resting systolic blood pressure \>180 mmHg or diastolic blood pressure \>110 mmHg despite optimal medical management)
   11. Complete left or right bundle branch block
   12. Severe aortic stenosis

Where this trial is running

Baltimore, Maryland and 57 other locations

• John Hopkins School of Medicine — Baltimore, Maryland, United States (NOT_YET_RECRUITING)
• Umass Memorial Health Care Systems — Worcester, Massachusetts, United States (NOT_YET_RECRUITING)
• Roswell Park Cancer Institute — Buffalo, New York, United States (WITHDRAWN)
• Weill Cornell — New York, New York, United States (NOT_YET_RECRUITING)
• Westchester Medical College — Valhalla, New York, United States (WITHDRAWN)
• Clinical Research Allicance — Westbury, New York, United States (RECRUITING)
• Spoknwrd Clinical Trials Inc. — Easton, Pennsylvania, United States (NOT_YET_RECRUITING)
• The Methodist Hospital Research Institute — Houston, Texas, United States (NOT_YET_RECRUITING)
• The University of Texas MD Anderson Cancer Center — Houston, Texas, United States (NOT_YET_RECRUITING)
• Royal Adelaide Hospital — Adelaide, Australia (NOT_YET_RECRUITING)
• Austin Health — Australia, Australia (NOT_YET_RECRUITING)
• St. Vincent's Hospital Melbourne — Darlinghurst, Australia (NOT_YET_RECRUITING)
• The Alfred Hospital — Melbourne, Australia (NOT_YET_RECRUITING)
• Royal Perth Hospital — Perth, Australia (NOT_YET_RECRUITING)
• Gold Coast University Hospital — Southport, Australia (NOT_YET_RECRUITING)
• Westmead Hospital — Sydney, Australia (NOT_YET_RECRUITING)
• Hospital Erasto Gaertner - Liga Paranaense de Combate ao Cancer — Curitiba, Brazil (RECRUITING)
• Cetus Hospital Dia Oncologia — Minas Gerai, Brazil (RECRUITING)
• Hospital de Clínicas de Porto Alegre — Porto Alegre, Brazil (RECRUITING)
• Irmandade da Santa Casa de Misericórdia de Porto Alegre Centro Multidisciplinar de Pesquisa — Porto Alegre, Brazil (RECRUITING)
• INCA - Instituto Nacional de Câncer — Rio de Janeiro, Brazil (RECRUITING)
• "Fundacao Faculdade Regional de Medicina de Sao Jose do Rio Preto CIP - Centro Integrado de Pesquisa" — San Jose Rio Preto, Brazil (RECRUITING)
• Hospital Santa Marcelina — São Paulo, Brazil (RECRUITING)
• ICESP - Instituto do Câncer do Estado de São Paulo Octavio Frias de Oliveira — São Paulo, Brazil (RECRUITING)
• Peking Union Medical College Hospital — Beijing, China (NOT_YET_RECRUITING)
• Peking University Third Hospital — Beijing, China (RECRUITING)
• The First Hospital of Jilin University — Changchun, China (RECRUITING)
• Guangdong Provincial People's Hospital — Guangzhou, China (RECRUITING)
• Nanfang Hospital of Southern Medical University — Guangzhou, China (RECRUITING)
• Sun Yat-sen University Cancer center — Guangzhou, China (NOT_YET_RECRUITING)
• The First Affiliated Hosptial of Zhejiang University School of Medicine — Hangzhou, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Nanchang University — Nanchang, China (NOT_YET_RECRUITING)
• Zhong Da Hospital, Southeast University — Nanjing, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Guangxi Medical University — Nanning, China (RECRUITING)
• The Affiliated Hospital of Qingdao University — Qingdao, China (NOT_YET_RECRUITING)
• Huashan Hospital, Fudan University — Shanghai, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Soochow University — Suzhou, China (NOT_YET_RECRUITING)
• Hematology Hospital of the Chinese Academy of Medical Sciences — Tianjin, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Wenzhou Medical University — Wenzhou, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Jiaotong University — Xi'an, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Xiamen University — Xiamen, China (NOT_YET_RECRUITING)
• The Affiliated Hospital of Xuzhou Medical College — Xuzhou, China (NOT_YET_RECRUITING)
• The First Affiliated Hospital of Zhengzhou University — Zhengzhou, China (NOT_YET_RECRUITING)
• Inje University Haeundae Paik Hospital — Busan, South Korea (RECRUITING)
• Pusan National University Hospital — Busan, South Korea (RECRUITING)
• Kyungpook National University Hospital — Daegu, South Korea (NOT_YET_RECRUITING)
• Yeungnam University Hospital — Daegu, South Korea (RECRUITING)
• National Cancer Center — Goyang-si, South Korea (NOT_YET_RECRUITING)
• Gachon University Gil Medical Center — Incheon, South Korea (WITHDRAWN)
• Jeonbuk National University Hospital — Jeonju, South Korea (RECRUITING)

Study contacts

• Study coordinator: Contact for Trial Information

Conditions: Acute Myeloid Leukemia, Leukemia, acute myeloid leukemia, quizartinib, FLT3, allo-HSCT, leukemia