Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood

NCT03793478 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: AC220-A-U2022016-002919-18
• Study Type: interventional
• Target: 65
• Locations: 10 countries
• Sites: 27

Brief Summary

Quizartinib is an experimental drug. It is not approved for regular use. It can only be used in medical research. Children or young adults with a certain kind of blood cancer (FLT3-ITD AML) might be able to join this study if it has come back after remission or is not responding to treatment.

Conditions

Acute Myeloid Leukemia

Keywords

Acute myeloid leukemia recurrent; Relapsed or refractory; FMS-like tyrosine kinase 3 positive; Cancer of the blood; AML; FLT3-ITD mutation

Outcome Measures

Primary Outcomes (5)

• Number of dose-limiting toxicities (Phase 1)

  Re-induction Cycle 1 Day 1 up to Day 28 (each cycle is 28 days)

• Composite complete remission (CRc) rate among participants with acute myeloid leukemia (AML) (Phase 1 and 2)

  CRc rate is defined as percentage of participants with best response of complete remission (CR) or CR with incomplete hematological recovery (CRi) after completion of up to 2 re-induction cycles

  within 8 years, 8 months

• Pharmacokinetic parameter area under the concentration curve for quizartinib and AC886 (Phase 1 and 2)

  Re-induction Phase 1 and 2,Cycle 1: Days 6, 20:Predose, 1 hour (Phase 1 only), 2, 4, and 6 hours; Days 7 and 21:24 hours; Phase 1 and 2 Cycle 2: Days 6 and 20:predose, 3 hours; Continuation Cycle 1 Days 1 and 15:predose, 2-4 hours (each cycle, 28 days)

• Pharmacokinetic parameter apparent clearance (CL/F) for quizartinib and AC886 (Phase 1 and 2)

  Re-induction Phase 1 and 2,Cycle 1: Days 6, 20:Predose, 1 hour (Phase 1 only), 2, 4, and 6 hours; Days 7 and 21:24 hours; Phase 1 and 2 Cycle 2: Days 6 and 20:predose, 3 hours; Continuation Cycle 1 Days 1 and 15:predose, 2-4 hours (each cycle, 28 days)

• Pharmacokinetic parameter apparent volume of distribution (Vz/F) for quizartinib and AC886 (Phase 1 and 2)

  Re-induction Phase 1 and 2,Cycle 1: Days 6, 20:Predose, 1 hour (Phase 1 only), 2, 4, and 6 hours; Days 7 and 21:24 hours; Phase 1 and 2 Cycle 2: Days 6 and 20:predose, 3 hours; Continuation Cycle 1 Days 1 and 15:predose, 2-4 hours (each cycle, 28 days)

Secondary Outcomes (16)

• Complete remission (CR) rate among participants with AML (Phase 1 and 2)

  on Day 56 (± 3 Days) for the last subject, within 4 years

• Complete remission with incomplete recovery (CRi) rate among participants with AML (Phase 1 and 2)

  on Day 56 (± 3 Days) for the last subject, within 4 years

• Duration of CR among participants with AML (Phase 1 and 2)

  within 8 years, 8 months

• Duration of CRi among participants with AML (Phase 1 and 2)

  within 8 years, 8 months

• Duration of composite complete remission (CRc) among participants with AML (Phase 1 and 2)

  within 8 years, 8 months

Study Arms (1)

All Participants

EXPERIMENTAL

All participants will receive re-induction therapy that includes fludarabine and cytarabine in combination with experimental drug quizartinib. For prophylaxis, IT chemotherapy with cytarabine, methotrexate and prednisolone/hydrocortisone will be given prior to or between re-induction cycles. After completing re-induction therapy, eligible participants may also receive optional consolidation chemotherapy which includes cytarabine, etoposide and quizartinib, if HSCT is not available immediately. After completing re-induction or HSCT successfully, eligible participants can go on to receive continuation therapy with quizartinib.

Drug: Quizartinib; Drug: Fludarabine; Drug: Cytarabine; Drug: Intrathecal (IT) triple chemotherapy prophylaxis; Drug: Etoposide

Interventions

Quizartinib DRUG

Administered orally once daily starting on Day 6 and continuing through Day 28; Optional low intensity consolidation with chemotherapy: Administered orally once daily starting on Day 1 and continuing through Day 28

Also known as: Quizartinib dihydrochloride, Vanflyta

All Participants

Fludarabine DRUG

30 mg/m\^2/day IV infusion given over 30 minutes on Days 1 through 5 (administered based on body weight)

All Participants

Cytarabine DRUG

2000 mg/m\^2/day IV infusion given over 3 hours on Days 1 through 5 (begin 4 hours after the start of fludarabine) (administered in accordance with standard of care); Optional high intensity consolidation with chemotherapy and quizartinib: 500 mg/m\^2/day as a continuous 96-hour IV infusion on Days 1 through 4; Optional low intensity consolidation with chemotherapy: 75 mg/m\^2/day as once daily subcutaneous or IV on Days 1 through 4 and Days 15 through 18

All Participants

Intrathecal (IT) triple chemotherapy prophylaxis DRUG

IT cytarabine, methotrexate, and either prednisolone or hydrocortisone; doses are based on the participant's age and standard practice at each site

All Participants

Etoposide DRUG

Optional high intensity consolidation with chemotherapy and quizartinib: 100 mg/m\^2/dose once daily as an IV infusion over 3 hours on Days 1 through 5

All Participants

Eligibility Criteria

• Age: 1 Month - 21 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants must meet all of the following criteria to be eligible for enrollment into the study:
• Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
• In first relapse or refractory to first-line high-dose chemotherapy with no more than 1 attempt (1 to 2 cycles of induction chemotherapy) at remission induction - prior HSCT is permitted
• Has presence of the FLT3-ITD activating mutation in bone marrow or peripheral blood as defined in the protocol
• Is between 1 month and 21 years of age at the time the Informed Consent/Assent form is signed
• Has protocol-defined adequate performance status score
• Has fully recovered from the acute clinically significant toxicity effects of all prior chemotherapy, immunotherapy, or radiotherapy, per protocol guidelines
• Has protocol-defined adequate renal, hepatic and cardiac functions
• If of reproductive potential, is permanently sterile or agrees to use highly effective birth control upon enrollment, during the period of therapy, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later
• If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
• Male participants must be surgically sterile or willing to use highly effective birth control during the treatment period, and for 6 months following the last dose of quizartinib, etoposide, fludarabine, methotrexate, or cytarabine, whichever is later.
• Participant/legal representative is capable of understanding the investigational nature of the study, potential risks, and benefits, and the patient (and/or legal representative) signs a written assent/informed consent

You may not qualify if:

• Participants who meet any of the following criteria will be disqualified from entering the study:
• Has been diagnosed with isolated central nervous system relapse, acute promyelocytic leukemia (APL), juvenile myelomonocytic leukemia, French-American-British classification M3 or WHO classification of APL with translocation, or with myeloid proliferations related to Down syndrome
• Has uncontrolled or pre-defined significant cardiovascular disease as detailed in the protocol
• Has systemic fungal, bacterial, viral or other infection that is exhibiting ongoing signs/symptoms related to the infection without improvement despite appropriate antibiotics or other treatment. The patient must be off vasopressors and have negative blood cultures for at least 48 hours prior to the start of systematic protocol therapy.
• Has known active clinically relevant liver disease (e.g., active hepatitis B or active hepatitis C)
• Has known history of human immunodeficiency virus (HIV)
• Has history of hypersensitivity to any of the study medications or their excipients
• Is receiving or is anticipated to receive concomitant chemotherapy, radiation, or immunotherapy other than as specified in the protocol
• Has any significant concurrent disease, illness, psychiatric disorder or social issue that would compromise subject safety or compliance, interfere with consent/assent, study participation, follow up, or interpretation of study results
• Is currently participating in another investigative interventional procedure (observational or long-term interventional follow-up is allowed)
• Is otherwise considered inappropriate for the study by the Investigator

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Innovative Therapies For Children with Cancer Consortium: collaborator
• Children's Oncology Group: collaborator

Study Sites (27)

Loma Linda University Cancer Center

Loma Linda, California, 92354, United States

Location

University of California, San Francisco

San Francisco, California, 94158, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

A.I. duPont Hospital for Children

Wilmington, Delaware, 19803, United States

Location

Children's National Medical Center

Washington D.C., District of Columbia, 20010, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

University of Minnesota/Masonic Cancer Center

Minneapolis, Minnesota, 55455, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

UPMC Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

The University of Texas Southwestern Medical Center Children's Health

Dallas, Texas, 75390, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Universitair Ziekenhuis Gent

Ghent, Belgium

Location

The Hospital for Sick Children

Toronto, Ontario, M5G1X8, Canada

Location

British Columbia Children's Hospital

Vancouver, V6H 3V4, Canada

Location

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Centre Léon Bérard

Lyon, 69008, France

Location

Hôpital Armand-Trousseau

Paris, 75012, France

Location

Hôpital des Enfants

Toulouse, 31300, France

Location

Rambam Medical Center

Haifa, 31096, Israel

Location

Tel Aviv Sourasky Medical Center

Tel Aviv, 64239, Israel

Location

Fondazione IRCCS San Gerardo dei Tintori

Monza, 20900, Italy

Location

IRCCS Ospedale Pediatrico Bambino Gesù

Rome, 00165, Italy

Location

Ospedale Infantile Regina Margherita

Torino, 10126, Italy

Location

Prinses Maxima Centrum voor Kinderoncologie

Utrecht, 3584 EA, Netherlands

Location

Hospital Infantil Universitario Nino Jesus

Madrid, 28009, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och Ungdomssjukhus

Gothenburg, 41685, Sweden

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

quizartinib; fludarabine; Cytarabine; Etoposide

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: A single group will progress through a multiple phase study design as described in the detailed description.

Study Record Dates

• First Submitted: January 2, 2019
• First Posted: January 4, 2019
• Study Start: August 15, 2018
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): May 1, 2027
• Last Updated: April 1, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.

Locations

SE (1); DK (1); BE (1); IL (2); US (11); FR (3); IT (3); NL (1); ES (2); CA (2)