Daunorubicin or Idarubicin With Cytarabine Plus Quizartinib vs Physician's Choice in Newly Diagnosed FLT3-ITD+ AML

NCT04676243 | Withdrawn Phase 3 DMC

• 1 other identifier: HeLeNe 20-04
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The orally administered second-generation bis-aryl urea tyrosine kinase inhibitor quizartinib is very specific for FLT3, has a high capacity for sustained FLT3-inhibition and an acceptable toxicity profile. Furthermore, single agent quizartinib doubled the response rate as compared to standard of care in a randomized study in r/r-AML. Combination therapy of quizartinib with intensive standard induction chemotherapy has been shown to be safe and moreover, single agent quizartinib maintenance therapy is feasible even after allogeneic HCT. The efficacy of quizartinib in combination with intensive induction and post-remission therapy including allogeneic HCT and single agent quizartinib as maintenance therapy is evaluated by this protocol. This approach is compared in a randomized manner to the current standard of care.

Conditions

Acute Myeloid Leukemia

Keywords

AML newly diagnosed; Quizartinib added to SOC; FLT3-ITD positivity

Outcome Measures

Primary Outcomes (1)

• Modified Event-free survival (mEFS)

  mEFS is defined as the time from randomization until one of the following events, whichever occurs first: a) failure to obtain complete remission (CR) or complete remission with incomplete hematological recovery (CRi) or CR with partial recovery of peripheral blood counts (CRh) after induction therapy including one or two induction treatment cycles limited to an observational period of maximally 100 days, b) relapse from CR/CRi/CRh or c) death from any cause.

  through study completion (up to 4 years), from randomization until occurence of event a) b) or c) on individial patients' basis

Secondary Outcomes (3)

• Overall survival (OS)

  through study completion (up to 4 years), frome randomization until death from any cause

• Composite remission

  End of induction therapy, between 4 and 12 weeks

• Measurable residual disease (MRD)

  End of induction thearpy (28-84 days from randomization), End of consolidation therapy (140-222 days from randomization), End of maintenance therapy (140-1,120 days from randomization)

Study Arms (2)

Quizartinib plus standard of care (SOC)

EXPERIMENTAL

Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Quizartinib

Drug: Quizartinib; Drug: Standard of Care Chemotherapy

Physician's choice

ACTIVE COMPARATOR

Physician's choice (usually Daunorubicin/ Cytarabine or Idarubicin/Cytarabine and Midostaurin)

Drug: Treatment according to Physician's Choice

Interventions

Quizartinib DRUG

20 mg coated tablets, orally administered

Also known as: Drug Code:AC220

Quizartinib plus standard of care (SOC)

Treatment according to Physician's Choice DRUG

Usually daunorubicin/ cytarabine or idarubicin/Cytarabine plus FLT3 inhibitor (usually midostaurin)

Also known as: PhC

Physician's choice

Standard of Care Chemotherapy DRUG

Daunorubicin/ Cytarabine or Idarubicin/Cytarabine

Also known as: SOC

Quizartinib plus standard of care (SOC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of untreated acute myeloid leukemia (AML) according to the WHO 2016 definition
• Positive for FLT3-ITD (defined as a ratio of mutant to wild-type alleles of at least 0.05; measured within 4 weeks before randomization)
• No prior chemotherapy for leukemia except hydroxyurea to control hyperleukocytosis before randomization (≤7 days) \*
• Age ≥18 years, no upper age limit
• ECOG PS ≤2. (Eastern Cooperative Oncology Group performance status)
• Adequate renal function defined as creatinine clearance \>50 mL/min (calculated using the standard method of the local institution)
• Considered eligible to receive intensive chemotherapy as per investigator judgment
• No contraindications for FLT3-inhibitor therapy
• No severe organ function abnormalities
• Not included in other first-line trials
• Non-pregnant and non-nursing women
• Women of childbearing potential (WOCBP) must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 48 hours prior to randomization. ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
• WOCBP must agree to avoid getting pregnant while on therapy: WOCBP must either commit to continued abstinence from heterosexual intercourse or begin and adhere to one acceptable method of birth control (IUD, tubal ligation, or partner's vasectomy) during study and 6 months after end of study/treatment.\*\*
• Men must use a latex condom during any sexual contact with WOCBP, even if they have undergone a successful vasectomy and must agree to avoid to father a child during study and 6 months after end of study/treatment
• Signed written informed consent

You may not qualify if:

• AML with PML-RARA or BCR-ABL1
• Patients with known active central nervous system (CNS) leukemia (assessed clinically).
• Isolated extramedullary manifestation of AML
• Patients with a "currently active" second malignancy other than non-melanoma skin cancer. Patients are not considered to have a "currently active" malignancy if they have completed therapy for more than one year and are considered by their physician to be at less than 30% risk of relapse within one year.
• Prior treatment for AML, except for the following allowances:
• Leukapheresis;
• Treatment for hyperleukocytosis with hydroxyurea;
• Cranial radiotherapy for central nervous system (CNS) leukostasis;
• Prophylactic intrathecal chemotherapy;
• Growth factor/cytokine support;
• Uncontrolled or significant cardiovascular disease, including any of the following:
• History of heart failure NYHA class 3 or 4
• Left ventricular ejection fraction (LVEF) ≤40% by echocardiogram (ECHO)
• History of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
• History of second (Mobitz II) or third degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)

Sponsors & Collaborators

• University Hospital Heidelberg: lead
• Daiichi Sankyo Europe, GmbH, a Daiichi Sankyo Company: collaborator

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

quizartinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• Richard F Schlenk, Prof Dr

  NCT Trial Center, University Heidelberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant medical director

Model Details: multicenter, randomized phase in patients with FLT3-ITD positive AML comparing quizartinib in combination with SOC chemotherapy versus treatment according to physician's choice (PhC).

Study Record Dates

• First Submitted: December 9, 2020
• First Posted: December 19, 2020
• Study Start: May 1, 2022
• Primary Completion: May 1, 2025
• Study Completion: December 1, 2025
• Last Updated: May 25, 2022

Record last verified: 2022-05

Data Sharing

• IPD Sharing: Will not share