Acute Myeloid Leukemia Clinical Trial
Official title:
A Phase 1/2, Multicenter, Dose-Escalating Study To Evaluate the Safety, Pharmacokinetics, Pharmacodynamics, and Efficacy Of Quizartinib Administered in Combination With Re-Induction Chemotherapy, and as a Single-Agent Continuation Therapy, in Pediatric Relapsed/Refractory AML Subjects Aged 1 Month to <18 Years (and Young Adults Aged up to 21 Years) With FLT3-ITD Mutations
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.
Status | Recruiting |
Enrollment | 65 |
Est. completion date | May 1, 2027 |
Est. primary completion date | May 1, 2027 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 1 Month to 21 Years |
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 |
Country | Name | City | State |
---|---|---|---|
Belgium | Universitair Ziekenhuis Gent | Gent | |
Canada | Montreal Children's Hospital | Montréal | Quebec |
Canada | The Hospital for Sick Children | Toronto | Ontario |
Canada | British Columbia Children's Hospital | Vancouver | |
Denmark | Rigshospitalet | Copenhagen | |
France | Centre Léon Bérard | Lyon | |
France | Hôpital Armand-Trousseau | Paris | |
France | Hôpital des Enfants | Toulouse | |
Israel | Rambam Medical Center | Haifa | |
Israel | Schneider Children's Medical Center of Israel | Petah Tikva | |
Israel | Tel Aviv Sourasky Medical Center | Tel Aviv-Yafo | |
Italy | Fondazione IRCCS San Gerardo dei Tintori | Monza | |
Italy | IRCCS Ospedale Pediatrico Bambino Gesù | Rome | |
Italy | Ospedale Infantile Regina Margherita | Torino | |
Netherlands | Prinses Maxima Centrum voor Kinderoncologie | Utrecht | |
Spain | Hospital Infantil Universitario Nino Jesus | Madrid | |
Spain | Hospital Universitario La Paz | Madrid | |
Sweden | Sahlgrenska Universitetssjukhuset - Drottning Silvias Barn- och Ungdomssjukhus | Göteborg | |
United Kingdom | NHS Greater Glasgow and Clyde - The Queen Elizabeth University Hospital | Glasgow | |
United States | Children's Healthcare of Atlanta | Atlanta | Georgia |
United States | Children's Hospital Colorado | Aurora | Colorado |
United States | Johns Hopkins | Baltimore | Maryland |
United States | Cincinnati Children's Hospital Medical Center | Cincinnati | Ohio |
United States | The University of Texas Southwestern Medical Center Children's Health | Dallas | Texas |
United States | Riley Hospital for Children - Indiana University | Indianapolis | Indiana |
United States | University of Mississippi Medical Center | Jackson | Mississippi |
United States | Loma Linda University Cancer Center | Loma Linda | California |
United States | University of Minnesota/Masonic Cancer Center | Minneapolis | Minnesota |
United States | Columbia University/Herbert Irving Cancer Center | New York | New York |
United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
United States | UPMC Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
United States | Washington University School of Medicine | Saint Louis | Missouri |
United States | University of California, San Francisco | San Francisco | California |
United States | Seattle Children's Hospital | Seattle | Washington |
United States | New York Medical College | Valhalla | New York |
United States | Children's National Medical Center | Washington | District of Columbia |
United States | A.I. duPont Hospital for Children | Wilmington | Delaware |
Lead Sponsor | Collaborator |
---|---|
Daiichi Sankyo, Inc. | Children's Oncology Group, Innovative Therapies For Children with Cancer Consortium |
United States, Belgium, Canada, Denmark, France, Israel, Italy, Netherlands, Spain, Sweden, United Kingdom,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of dose-limiting toxicities (Phase 1) | Re-induction Cycle 1 Day 1 up to Day 28 (each cycle is 28 days) | ||
Primary | 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 | |
Primary | 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) | ||
Primary | 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) | ||
Primary | 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 | Complete remission (CR) rate among participants with AML (Phase 1 and 2) | CR rate is defined as the percentage of participants achieving CR after completion of up to 2 re-induction cycles | on Day 56 (± 3 Days) for the last subject, within 4 years | |
Secondary | Complete remission with incomplete recovery (CRi) rate among participants with AML (Phase 1 and 2) | CRi rate is defined as the percentage of participants achieving CRi after completion of up to 2 re-induction cycles | on Day 56 (± 3 Days) for the last subject, within 4 years | |
Secondary | Duration of CR among participants with AML (Phase 1 and 2) | Duration of CR is defined as the time from the first documented CR until documented relapse | within 8 years, 8 months | |
Secondary | Duration of CRi among participants with AML (Phase 1 and 2) | Duration of CRi is defined as the time from the first documented CRi until documented relapse | within 8 years, 8 months | |
Secondary | Duration of composite complete remission (CRc) among participants with AML (Phase 1 and 2) | Duration of CRc is defined as the time from the first documented CR or CRi until documented relapse | within 8 years, 8 months | |
Secondary | Complete remission (CR) rate after completion of re-induction Cycle 1 among participants with AML (Phase 1 and 2) | CR rate after completion of re-induction Cycle 1 is defined as the percentage of participants achieving a CR after completion of re-induction Cycle 1 | on Day 56 (± 3 Days) for the last subject, within 4 years | |
Secondary | Complete remission with incomplete recovery (CRi) rate after completion of re-induction Cycle 1 among participants with AML (Phase 1 and 2) | CRi rate after completion of re-induction Cycle 1 is defined as the percentage of participants achieving a CRi after completion of re-induction Cycle 1 | on Day 56 (± 3 Days) for the last subject, within 4 years | |
Secondary | Composite complete remission (CRc) rate after completion of re-induction Cycle 1 among participants with AML (Phase 1 and 2) | CRc rate after completion of re-induction Cycle 1 is defined as the percentage of participants achieving CRc after completion of re-induction Cycle 1 | on Day 56 (± 3 Days) for the last subject, within 4 years | |
Secondary | Time to relapse among participants with AML (Phase 1 and 2) | Time to relapse is defined as the time from the first documented response (CR, CRi) until documented relapse | within 8 years, 8 months | |
Secondary | Rate of relapse among participants with AML after 1, 2 and 3 years (Phase 1 and 2) | Rate of relapse is defined as the percentage of participants who achieved CRc at the end of re-induction and had relapsed at 3 categorical time points Categories: 1 year, 2 years, 3 years | within 8 years, 8 months | |
Secondary | Cumulative incidence of relapse among participants with AML at the end of study (Phase 1 and 2) | Cumulative incidence of relapse at the end of the study is defined as the percentage of participants who achieved CRc at the end of re-induction and relapsed by the end of the study | within 8 years, 8 months | |
Secondary | Overall survival among participants with AML at 1, 2, and 3 years (Phase 1 and 2) | Overall survival is defined as the time from the start of re-induction therapy until death from any cause | within 8 years, 8 months | |
Secondary | Event-free survival among participants with AML at 1, 2, and 3 years (Phase 1 and 2) | Event-free survival is defined as the time from the start of re-induction therapy until the earliest date of the following:
Refractory disease at the end of re-induction Relapse after CR or CRi Death from any cause at any time during the study |
within 8 years, 8 months | |
Secondary | Number of participants proceeding to high-dose conditioning therapy/allogeneic hematopoietic stem cell transplantation (HSCT) (including transplant-related mortality) among participants with AML (Phase 1 and 2) | within 8 years, 8 months | ||
Secondary | Rate of CRc (CR or CRi) without minimal residual disease (MRD) using next generation sequencing among participants with AML (Phase 1 and 2) | MRD is defined as the presence of leukemic cells in the bone marrow detected above a predefined cut-off level by a validated assay in participants who achieved a CR or CRi
Categories: at screening, at re-induction cycle 1, at re-induction cycle 2, at time of relapse |
within 8 years, 8 months | |
Secondary | Acceptability of including the palatability of quizartinib formulations among participants with AML (Phase 1 and 2) | Acceptability is assessed by palatability using a 5-point hedonic scale (from "Super bad" to "Super good") for participants who are developmentally able to answer. If unable, the caregiver provides information in a free text field stating whether the participant spit it out, may not have liked the flavor, etc. | within 8 years, 8 months |
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