Active, not recruiting
Phase 1/2
Safety and Efficacy of Quizartinib in Children and Young Adults With Acute Myeloid Leukemia (AML), a Cancer of the Blood
Condition(s) studied
Acute Myeloid Leukemia
Investigational drug(s) / intervention(s)
Quizartinib: 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
Fludarabine: 30 mg/m\^2/day IV infusion given over 30 minutes on Days 1 through 5 (administered based on body weight)
Cytarabine: 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
Intrathecal (IT) triple chemotherapy prophylaxis: IT cytarabine, methotrexate, and either prednisolone or hydrocortisone; doses are based on the participant's age and standard practice at each site
Etoposide: 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
Study 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.
Eligibility
Inclusion Criteria:
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
Exclusion Criteria:
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
Primary outcome measure(s)
- 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) — within 8 years, 8 months
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
- 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)
Trial sites (27)
| Facility | City | Region | Status |
| Loma Linda University Cancer Center |
Loma Linda |
California |
|
| University of California, San Francisco |
San Francisco |
California |
|
| Children's Hospital Colorado |
Aurora |
Colorado |
|
| A.I. duPont Hospital for Children |
Wilmington |
Delaware |
|
| Children's National Medical Center |
Washington D.C. |
District of Columbia |
|
| Children's Healthcare of Atlanta |
Atlanta |
Georgia |
|
| University of Minnesota/Masonic Cancer Center |
Minneapolis |
Minnesota |
|
| Cincinnati Children's Hospital Medical Center |
Cincinnati |
Ohio |
|
| UPMC Children's Hospital of Pittsburgh |
Pittsburgh |
Pennsylvania |
|
| The University of Texas Southwestern Medical Center Children's Health |
Dallas |
Texas |
|
| Seattle Children's Hospital |
Seattle |
Washington |
|
| Universitair Ziekenhuis Gent |
Ghent |
Belgium |
|
| The Hospital for Sick Children |
Toronto |
Ontario |
|
| British Columbia Children's Hospital |
Vancouver |
Canada |
|
| Rigshospitalet |
Copenhagen |
Denmark |
|
| Centre Léon Bérard |
Lyon |
France |
|
| Hôpital Armand-Trousseau |
Paris |
France |
|
| Hôpital des Enfants |
Toulouse |
France |
|
| Rambam Medical Center |
Haifa |
Israel |
|
| Tel Aviv Sourasky Medical Center |
Tel Aviv |
Israel |
|
| Fondazione IRCCS San Gerardo dei Tintori |
Monza |
Italy |
|
| IRCCS Ospedale Pediatrico Bambino Gesù |
Rome |
Italy |
|
| Ospedale Infantile Regina Margherita |
Torino |
Italy |
|
| Prinses Maxima Centrum voor Kinderoncologie |
Utrecht |
Netherlands |
|
| Hospital Infantil Universitario Nino Jesus |
Madrid |
Spain |
|
| Hospital Universitario La Paz |
Madrid |
Spain |
|
| Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och Ungdomssjukhus |
Gothenburg |
Sweden |
|
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