Acute Myeloid Leukemia
Conditions
Keywords
Relapsed/Refractory, Newly Diagnosed, Unfit for Chemotherapy, Positive for FLT3-ITD Mutation
Brief summary
Participants with AML that have gone into remission and come back (relapsed) or gone into remission with a number of leukemia cells still in their system (refractory) will be recruited for this study. They will also be positive for FLT3-ITD mutation. Participants will receive a combined dose of quizartinib and milademetan that have not been approved by the US Food and Drug Administration yet (m). The combination of these drugs will be provided in different amounts on defined days (dosing schedules). It is expected that the combination of milademetan and quizartinib will be safe and well tolerated. It is expected that the combination may fight the leukemia better than a single drug. The study will run for approximately 3 years. There may be up to 156 participants. The study has 2 parts: * Part 1 will test 24-36 participants in approximately 15 study centers globally. Participants will receive two study drugs (milademetan and quizartinib) in different amounts on specific days. Information will be gathered to see what dosing schedule of the drug combination is best (maximum tolerated/recommended dose). * Part 2 of the study will confirm the recommended dosing schedule identified in Part 1 is effective. A larger number of participants will receive the recommended dose in approximately 15 additional sites worldwide as necessary, based on the enrollment rate, the population, and the standard of care available to them at the time of enrollment.
Interventions
DRUGQuizartinib
20 or 30 mg tablets for oral administration
DRUGMilademetan
5, 20, 80 or 200 mg capsules for oral administration
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Part 1 Single Group 1 Arm, Part 2 Parallel, 2 Cohorts
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has reached ≥18 years old or the age of the age of majority in their country * Part 1 (dose escalation): Has FLT3-ITD mutant (≥ 3% FLT3-ITD/total FLT3) AML (primary AML, secondary, or therapy-related AML), and has treatment failure to prior AML therapy or have relapsed after prior AML therapy * Part 2 (dose expansion): Has FLT3-ITD mutant (≥3% FLT3-ITD/total FLT3) AML (primary, secondary, or therapy-related AML), and has treatment failure to prior AML therapy or have relapsed after prior AML therapy, OR has newly diagnosed AML who are ineligible for intensive induction chemotherapy * Has Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2 (or 3 for patients with newly diagnosed AML between 18 and 74 years old) * Has protocol-defined adequate renal, hepatic and cardiac status * Is not pregnant, and if not postmenopausal or a surgically sterile male or female, is willing to use a highly effective contraceptive method upon enrollment, during the course of the study, and for 6 months following the last dose of investigational drug * Is able and willing to provide protocol-defined bone marrow biopsies/aspirates
Exclusion criteria
* Has central nervous system (CNS) involvement of leukemia - patients with a history of CNS leukemia may be eligible if the CNS leukemia is adequately controlled (defined as no clinical symptoms of CNS disease and at least 2 consecutive lumbar punctures with no evidence of disease prior to study enrollment) after discussion and approval from the Sponsor * Has acute promyelocytic leukemia (AML subtype M3) * Has uncontrolled or significant cardiovascular disease or QTc interval \>450 ms (average of triplicate determination) * Has an uncontrolled infection requiring intravenous antibiotics, antivirals, or antifungals. * Has known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection based on positive tests during Screening * Has persistent, clinically significant \> Grade 1 non-hematologic toxicity from prior AML therapies * Has any history or medical condition, metastatic condition, drug/medication use or other condition that might, per protocol or in the opinion of the investigator, compromise: 1. safety or well-being of the participant or offspring 2. safety of study staff 3. analysis of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Combination With Quizartinib | Baseline up to 28 days (Cycle 1) from the start of study drug administration | A dose limiting toxicity (DLT) is defined as any non-hematological treatment-emergent adverse event (TEAE) unless incontrovertibly related to disease progression, intercurrent illness, or concomitant medication, that occurs during the DLT evaluation period (28 days) in each dose level cohort, and is Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, with exceptions specified: Grade 3 or higher aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels, OR elevation in total bilirubin ≥3.0 × upper limit of normal (ULN) that does not return to ≤Grade 2 elevation within 7 days. Absolute neutrophil count (ANC) \<0.5 × 10\^9/L, platelets \<20 × 10\^9/L, and marrow cellularity \<5% at 6 weeks or later from start of therapy without any evidence of leukemia. |
| Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Baseline up to 35 days after last dose of study drug, up to approximately 2 years 3 months | A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during the treatment period (from date of first dose up to 35 days after the last dose of the study treatment), having been absent at pretreatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment related to the pretreatment state, when the AE is continuous. AEs collected after 35 days after the last dose of study drug were not considered TEAEs unless they were treatment-related. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months | Based on European LeukemiaNet criteria, complete remission (CR) was bone marrow (BM) blasts \<5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10\^9/L, and platelet count ≥100×10\^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts \<5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR; Stable disease: absence of CR, CRi, MLFS, or PR, and criteria for progressive disease (PD) not met; Relapse (after CR/CRi): BM blasts ≥5%, or reappearance of leukemic blasts, or EMD development; and PD: increase in BM blast % and/or increase of absolute blast counts: \>50% increase in marrow blasts over baseline, \>50% increase in peripheral blasts, or new EMD. |
| Overall Response Rate Following Administration of Milademetan in Combination With Quizartinib | Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months | Overall response rate was defined as the number of participants with composite Complete Remission (CRc)+Morphological Leukemia Free State (MLFS)+Partial Remission (PR) based on the European LeukemiaNet criteria. Based on the European LeukemiaNet criteria, CRc was defined as complete remission (CR) as bone marrow (BM) blasts \<5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10\^9/L, and platelet count ≥100×10\^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts \<5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR. |
Countries
United States
Participant flow
Recruitment details
A total of 10 out of the 22 screened participants who met all inclusion criteria and no exclusion criteria were enrolled in the study at 8 clinic sites in the United States. Only Part 1 is reported since the study terminated prior to Part 2.
Participants by arm
| Arm | Count |
|---|---|
| Part 1, Cohort 1: Quizartinib + Milademetan Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 14 and quizartinib 30 mg QD. | 4 |
| Part 1, Cohort 1A: Quizartinib + Milademetan Participants with relapsed/refractory FLT3-ITD Mutant AML who received milademetan 90 mg daily (QD) Day 1 - Day 7 and quizartinib 30 mg QD. | 6 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 3 | 0 |
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | Other | 0 | 2 |
| Overall Study | Physician Decision | 0 | 1 |
| Overall Study | Study terminated by Sponsor | 0 | 1 |
Baseline characteristics
| Characteristic | Part 1, Cohort 1: Quizartinib + Milademetan | Total | Part 1, Cohort 1A: Quizartinib + Milademetan |
|---|---|---|---|
| Age, Continuous | 64 years | 64 years | 65 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 4 Participants | 9 Participants | 5 Participants |
| Region of Enrollment United States | 4 participants | 10 participants | 6 participants |
| Sex: Female, Male Female | 0 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 4 Participants | 8 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 1 / 6 |
| other Total, other adverse events | 4 / 4 | 6 / 6 |
| serious Total, serious adverse events | 4 / 4 | 3 / 6 |
Outcome results
Primary
Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib
A treatment-emergent adverse event (TEAE) is defined as an adverse event (AE) that emerges during the treatment period (from date of first dose up to 35 days after the last dose of the study treatment), having been absent at pretreatment; or reemerges during treatment, having been present at baseline but stopped prior to treatment; or worsens in severity after starting treatment related to the pretreatment state, when the AE is continuous. AEs collected after 35 days after the last dose of study drug were not considered TEAEs unless they were treatment-related.
Time frame: Baseline up to 35 days after last dose of study drug, up to approximately 2 years 3 months
Population: Treatment-emergent adverse events (irrespective of causality) were assessed in the Safety Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Gastrointestinal Disorders | 4 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Investigations | 3 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Ear and Labyrinth Disorders | 1 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Metabolism and Nutrition Disorders | 4 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any General Disorders and Administration Site Conditions | 3 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Musculoskeletal and Connective Tissue Disorders | 2 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Cardiac Disorders | 1 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Nervous System Disorders | 4 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Immune System Disorders | 1 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Psychiatric Disorders | 2 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Eye Disorders | 2 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Renal and Urinary Disorders | 1 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Infections and Infestations | 4 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Respiratory, Thoracic, and Mediastinal Disorders | 4 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Blood and Lymphatic System Disorders | 2 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Skin and Subcutaneous Tissue Disorders | 3 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Injury, Poisoning and Procedural Complications | 0 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Vascular Disorders | 3 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any TEAEs | 4 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Vascular Disorders | 1 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any TEAEs | 6 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Blood and Lymphatic System Disorders | 5 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Cardiac Disorders | 2 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Ear and Labyrinth Disorders | 1 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Eye Disorders | 0 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Gastrointestinal Disorders | 6 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any General Disorders and Administration Site Conditions | 5 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Immune System Disorders | 0 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Infections and Infestations | 1 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Injury, Poisoning and Procedural Complications | 3 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Investigations | 5 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Metabolism and Nutrition Disorders | 5 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Musculoskeletal and Connective Tissue Disorders | 4 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Nervous System Disorders | 3 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Psychiatric Disorders | 2 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Renal and Urinary Disorders | 2 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Respiratory, Thoracic, and Mediastinal Disorders | 4 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Any Treatment-emergent Adverse Events by System Organ Class Following Administration of Milademetan in Combination With Quizartinib | Any Skin and Subcutaneous Tissue Disorders | 5 Participants |
Primary
Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Combination With Quizartinib
A dose limiting toxicity (DLT) is defined as any non-hematological treatment-emergent adverse event (TEAE) unless incontrovertibly related to disease progression, intercurrent illness, or concomitant medication, that occurs during the DLT evaluation period (28 days) in each dose level cohort, and is Grade 3 or higher according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0, with exceptions specified: Grade 3 or higher aspartate aminotransferase (AST)/alanine aminotransferase (ALT) levels, OR elevation in total bilirubin ≥3.0 × upper limit of normal (ULN) that does not return to ≤Grade 2 elevation within 7 days. Absolute neutrophil count (ANC) \<0.5 × 10\^9/L, platelets \<20 × 10\^9/L, and marrow cellularity \<5% at 6 weeks or later from start of therapy without any evidence of leukemia.
Time frame: Baseline up to 28 days (Cycle 1) from the start of study drug administration
Population: Dose-limiting toxicities were assessed in the DLT Evaluable Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Combination With Quizartinib | 1 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Dose Limiting Toxicities (DLTs) Following Administration of Milademetan in Combination With Quizartinib | 0 Participants |
Secondary
Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib
Based on European LeukemiaNet criteria, complete remission (CR) was bone marrow (BM) blasts \<5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10\^9/L, and platelet count ≥100×10\^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts \<5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR; Stable disease: absence of CR, CRi, MLFS, or PR, and criteria for progressive disease (PD) not met; Relapse (after CR/CRi): BM blasts ≥5%, or reappearance of leukemic blasts, or EMD development; and PD: increase in BM blast % and/or increase of absolute blast counts: \>50% increase in marrow blasts over baseline, \>50% increase in peripheral blasts, or new EMD.
Time frame: Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months
Population: Best Overall Response was assessed in the Full Analysis Set.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Complete remission (CR) | 0 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Complete Remission with Partial Hematological Recovery (CRh) | 0 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Complete Remission with Incomplete Blood Count Recovery (CRi) | 1 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Morphologic Leukemia Free State (MLFS) | 0 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Partial Remission (PR) | 0 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Stable Disease (SD) | 1 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Relapse | 0 Participants |
| Part 1, Cohort 1: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Missing | 2 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Missing | 1 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Complete remission (CR) | 0 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Partial Remission (PR) | 0 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Complete Remission with Partial Hematological Recovery (CRh) | 0 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Relapse | 0 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Complete Remission with Incomplete Blood Count Recovery (CRi) | 3 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Stable Disease (SD) | 2 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Number of Participants With Best Overall Response Following Administration of Milademetan in Combination With Quizartinib | Morphologic Leukemia Free State (MLFS) | 0 Participants |
Secondary
Overall Response Rate Following Administration of Milademetan in Combination With Quizartinib
Overall response rate was defined as the number of participants with composite Complete Remission (CRc)+Morphological Leukemia Free State (MLFS)+Partial Remission (PR) based on the European LeukemiaNet criteria. Based on the European LeukemiaNet criteria, CRc was defined as complete remission (CR) as bone marrow (BM) blasts \<5%, absence of circulating blasts/blasts with Auer rods, absence of extramedullary disease (EMD), absolute neutrophil count (ANC) ≥1.0×10\^9/L, and platelet count ≥100×10\^9/L; CR with Incomplete Blood Count Recovery (CRi): all CR criteria except for residual neutropenia or thrombocytopenia; Morphologic Leukemia Free State (MLFS): BM blasts \<5%, absence of blasts with Auer rods, absence of EMD, and no hematologic recovery required; Partial Remission (PR): decrease of BM blast percentage by at least 50% (to 5% to 25%) and all criteria of CR.
Time frame: Baseline up to first documented response, disease progression, withdrawal, or death (whichever occurs first), up to approximately 2 years 3 months
Population: Overall response rate was assessed in the Full Analysis Set.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Part 1, Cohort 1: Quizartinib + Milademetan | Overall Response Rate Following Administration of Milademetan in Combination With Quizartinib | 1 Participants |
| Part 1, Cohort 1A: Quizartinib + Milademetan | Overall Response Rate Following Administration of Milademetan in Combination With Quizartinib | 3 Participants |