Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood
Acute Myeloid Leukemia
About this trial
This is an interventional treatment trial for Acute Myeloid Leukemia focused on measuring Acute myeloid leukemia recurrent, Relapsed or refractory, FMS-like tyrosine kinase 3 positive, Cancer of the blood, AML, FLT3-ITD mutation
Eligibility Criteria
Inclusion Criteria:
- Has diagnosis of AML according to the World Health Organization (WHO) 2008 classification with ≥5% blasts in bone marrow, with or without extramedullary disease
- Is 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 study drug or cytarabine, whichever is later
- If female of child-bearing potential, tests negative for pregnancy and agrees not to breast feed
- 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
- Meets protocol-specified guidelines before inclusion in the continuation therapy phase
Exclusion Criteria:
- Has been diagnosed with isolated central nervous system relapse, certain kinds of leukemia, 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
Sites / Locations
- Loma Linda University Cancer CenterRecruiting
- University of California, San FranciscoRecruiting
- Children's Hospital ColoradoRecruiting
- A.I. duPont Hospital for ChildrenRecruiting
- Children's National Medical CenterRecruiting
- Children's Healthcare of AtlantaRecruiting
- Riley Hospital for Children - Indiana UniversityRecruiting
- Johns HopkinsRecruiting
- University of Minnesota/Masonic Cancer CenterRecruiting
- University of Mississippi Medical CenterRecruiting
- Washington University School of Medicine
- Columbia University/Herbert Irving Cancer CenterRecruiting
- New York Medical College
- Cincinnati Children's Hospital Medical CenterRecruiting
- Children's Hospital of Philadelphia
- UPMC Children's Hospital of PittsburghRecruiting
- The University of Texas Southwestern Medical Center Children's HealthRecruiting
- Seattle Children's HospitalRecruiting
- Universitair Ziekenhuis GentRecruiting
- The Hospital for Sick ChildrenRecruiting
- Montreal Children's HospitalRecruiting
- British Columbia Children's HospitalRecruiting
- RigshospitaletRecruiting
- Centre Léon BérardRecruiting
- Hôpital Armand-TrousseauRecruiting
- Hôpital des EnfantsRecruiting
- Rambam Medical CenterRecruiting
- Schneider Children's Medical Center of Israel
- Tel Aviv Sourasky Medical CenterRecruiting
- Fondazione IRCCS San Gerardo dei TintoriRecruiting
- IRCCS Ospedale Pediatrico Bambino GesùRecruiting
- Ospedale Infantile Regina MargheritaRecruiting
- Prinses Maxima Centrum voor KinderoncologieRecruiting
- Hospital Infantil Universitario Nino JesusRecruiting
- Hospital Universitario La PazRecruiting
- Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och UngdomssjukhusRecruiting
- NHS Greater Glasgow and Clyde - The Queen Elizabeth University Hospital
Arms of the Study
Arm 1
Experimental
All Participants
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.