Acute Myeloid Leukemia Clinical Trial
Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood
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.
The medical condition being investigated is relapsed or refractory AML in participants aged ≥1 month to ≤21 years with Feline McDonough Sarcoma (FMS)-like tyrosine kinase 3 (FLT3)-internal tandem duplication (ITD) mutations (FLT3-ITD AML), following failure of front-line intensive chemotherapy.
The trial will be conducted in multiple phases. An independent data monitoring committee (DMC) will protect the rights, safety, and well-being of participants by monitoring the progress and results. The DMC will comprise qualified physicians and scientists who are not Investigators in the study and not otherwise directly associated with the Sponsor and will be convened at the end of Phase 1.
A. Dose Escalation/De-escalation Phase:
Number of participants is determined by age group. Participants will be enrolled by dose-level to determine the recommended Phase 2 dose (RP2D) of quizartinib for pediatric participants that provides similar exposure to adult patients treated at the target adult dose of 60 mg orally once daily.
B. Dose-Expansion Phase:
Participants will receive the RP2D of quizartinib for their respective age group.
During both dose escalation and dose expansion phases, participants will receive:
Intrathecal (IT) triple chemotherapy prophylaxis prior to and between cycles
In re-induction Cycles 1 and 2, fludarabine/cytarabine (FLA) followed by quizartinib as a single agent
Allogeneic Hematopoietic Stem Cell Transplantation (HSCT) Period:
After re-induction therapy, participants will be evaluated for eligibility to undergo allogeneic hematopoietic stem cell transplant (HSCT). Eligible participants may receive a single 28-day cycle of consolidation therapy (standard of care chemotherapy with or without quizartinib) if an allogeneic HSCT is not available immediately. The options for consolidation therapy are as follows:
High intensity chemotherapy with quizartinib, or
Low intensity chemotherapy alone, or
Low intensity therapy with quizartinib as a single agent
Participants in remission after HSCT, or who are not eligible for HSCT but achieve at least a partial remission (PR) after re-induction, will receive up to 12 continuous 28-day cycles of quizartinib continuation therapy at the same dose received during re-induction in the dose expansion phase.
The long-term follow-up phase begins upon completion of 12 cycles of quizartinib Continuation Therapy or permanent discontinuation of quizartinib at any time. After completion of the 30-day safety follow-up visit, subsequent visits will occur at the following frequencies to assess survival and anti-leukemic treatments:
every 3 months for the first 2 years, and then
once a year thereafter until the last participant enrolled has been followed for three years from the date of enrollment
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
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
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There are 36 Locations for this study
Loma Linda California, 92354, United States More Info
San Francisco California, 94158, United States More Info
Aurora Colorado, 80045, United States More Info
Wilmington Delaware, 19803, United States More Info
Washington District of Columbia, 20010, United States More Info
Atlanta Georgia, 30322, United States More Info
Indianapolis Indiana, 46202, United States More Info
Baltimore Maryland, 21287, United States More Info
Minneapolis Minnesota, 55455, United States More Info
Jackson Mississippi, 39216, United States More Info
Saint Louis Missouri, 63110, United States
New York New York, 10032, United States More Info
Valhalla New York, 10595, United States
Cincinnati Ohio, 45229, United States More Info
Philadelphia Pennsylvania, 19104, United States
Pittsburgh Pennsylvania, 15224, United States More Info
Dallas Texas, 75390, United States More Info
Seattle Washington, 98105, United States More Info
Gent , , Belgium More Info
Toronto Ontario, M5G1X, Canada More Info
Montréal Quebec, H4A3J, Canada More Info
Vancouver , V6H 3, Canada More Info
Copenhagen , 2100, Denmark More Info
Lyon , 69008, France More Info
Paris , 75012, France More Info
Toulouse , 31300, France More Info
Haifa , 31096, Israel More Info
Petah Tikva , 49202, Israel
Tel Aviv-Yafo , 64239, Israel More Info
Monza , 20900, Italy More Info
Rome , 00165, Italy More Info
Torino , 10126, Italy More Info
Utrecht , 3584 , Netherlands More Info
Madrid , 28009, Spain More Info
Madrid , 28046, Spain More Info
Göteborg , 41685, Sweden More Info
Glasgow , G51 4, United Kingdom
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