Acute Myeloid Leukemia
Conditions
Keywords
AML, AC220, acute, FLT3, inhibitor, kinase, leukemia, leukaemia, myeloid, relapsed, refractory
Brief summary
AC220 will be administered as a once daily oral solution given continuously as 28-day treatment cycles, without any rest periods, until disease progression, relapse, intolerance to the drug, or elective allogeneic hematopoietic stem cell transplantation (HSCT).
Interventions
DRUGCompound AC220
Precomplexed powder in bottle formulation supplied as 200 mg in a 60 cc polyethylene terephthalate (PET) plastic bottle. Requires reconstitution by a pharmacist, must be stored securely, and protected from light.
Sponsors
Daiichi Sankyo
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Current enrollment is open only to FLT3-ITD positive, Cohort 1. Inclusion Criteria: 1. Males and females age ≥18 years in second relapse or refractory. 2. Males and females age ≥60 years in first relapse or refractory. 3. Must have baseline bone marrow sample taken. 4. Morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS with ≥20% bone marrow or peripheral blasts), as defined by the World Health Organization (WHO) criteria, confirmed by pathology review at treating institution. 5. Able to swallow the liquid study drug. 6. Eastern Cooperative Oncology Group performance status of 0 to 2 7. In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration will be at least 2 weeks for cytotoxic agents or at least 5 half-lives for noncytotoxic agents. The use of chemotherapeutic or antileukemic agents other than hydroxyurea is not permitted during the study with the possible exception of intrathecal (IT) therapy at the discretion of the Investigator and with the agreement of the Sponsor. 8. Persistent chronic clinically significant non-hematological toxicities from prior treatment must be ≤Grade 1. 9. Prior therapy with FLT3 inhibitors is permitted, except previous treatment with AC220. 10. Serum creatinine ≤1.5 × upper limit of normal (ULN) and glomerular filtration rate (GFR) \> 30 mL/min 11. Serum potassium, magnesium, and calcium levels should be at least within institutional normal limits. 12. Total serum bilirubin ≤1.5 × ULN 13. Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) ≤2.5 × ULN 14. Females of childbearing potential must have a negative pregnancy test (urine β-hCG). 15. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study. 16. Written informed consent must be provided.
Exclusion criteria
1. Patients over the age of 85 years except at the discretion of the Investigator and with agreement of the Sponsor. 2. Diagnosis of acute promyelocytic leukemia 3. Diagnosis of chronic myelogenous leukemia (CML) in blast crisis 4. AML in relapse or refractory after 3 or more previous lines of chemotherapy (and/or HSCT) treatment 5. AML or antecedent MDS secondary to prior chemotherapy 6. Persistent clinically significant non-hematological toxicity that is Grade \>1 by NCI CTCAE v4 from prior chemotherapy 7. Patients who have had HSCT and are within 100 days of transplant and/or are still taking immunosuppressive drugs and/or have clinically significant graft-versus-host disease requiring treatment and/or have \>Grade 1 persistent non hematological toxicity related to the transplant 8. Clinically active central nervous system (CNS) leukemia. Patients with CNS leukemia, which is controlled, but who are still receiving IT therapy at study entry may be considered eligible and continue receive IT therapy at the discretion of the Investigator and with agreement of the Sponsor. 9. Patients who have previously received AC220 10. Disseminated intravascular coagulation (DIC) (diagnosis by laboratory or clinical assessment) 11. Major surgery within 4 weeks prior to enrollment in the study 12. Radiation therapy within 4 weeks prior to, or concurrent with study 13. Use of concomitant drugs that prolong the time between the start of the Q wave and the end of the T wave (QT)/corrected interval between the Q wave and T wave (QTc) interval and/or are CYP3A4 inhibitors are prohibited with the exception of antibiotics, antifungals, and other antimicrobials that are used as standard of care to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the patient. 14. Uncontrolled or significant cardiovascular disease 15. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential 16. Men who are unwilling to use contraception if their partners are of childbearing potential 17. Active, uncontrolled infection 18. Human immunodeficiency virus positivity 19. Active hepatitis B or C or other active liver disease 20. History of cancer, except Stage 1 cervix or nonmelanotic skin cancer, with the possible exception of patients in complete remission
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Within the first 3 cycles of treatment (84 days) | Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[+\] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission. |
| Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Within the first 3 cycles of treatment (84 days) | Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[-\] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission. |
| Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status | within 28 months | CRc is defined as composite complete remission (CR+CRp+CRi) - CR = complete remission; CRp = complete remission with incomplete platelet recovery; CRi = complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia = all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib = all criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Any Response in FLT3-ITD (-) Participants | From the time of any response until disease progression or death, up to approximately 3 years post treatment | Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population). |
| Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants | From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment | Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population). |
| Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants | From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment | Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population). |
| Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data | From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment | Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of \>1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria. |
| Median Duration of Overall Survival in FLT3-ITD (-) Participants | Time from first dose to death from any cause, up to approximately 3 years post treatment | Kaplan-Meier analysis of overall survival (Safety Population) |
| Early Treatment-related Death | Within first 3 cycles of treatment (84 days) | Early treatment-related deaths included all treatment-related deaths prior to the end of Cycle 3 with a 3-day window (Cycle 3 end date + 3 days), unless the death was following a CRc response assessed by the Investigator. |
| Median Duration of Overall Survival in FLT3-ITD (+) Participants | Time from first dose to death from any cause, up to 3 years post treatment | Kaplan-Meier analysis of overall survival (Safety Population) |
| Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data | From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment | Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of \>1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria. |
| Duration of Any Response in FLT3-ITD (+) Participants | From the time of any response until disease progression or death, up to approximately 3 years post treatment | Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population). |
Countries
Canada, France, Germany, Italy, Netherlands, Poland, Spain, United Kingdom, United States
Participant flow
Recruitment details
A total of 333 participants from 9 countries (United States, Germany, France, Italy, United Kingdom, Spain, Netherlands, Canada, and Poland) who met all inclusion and none of the exclusion criteria were included in the study.
Pre-assignment details
All participants in both cohorts initially received a starting dose of 200 mg/day quizartinib (maximum tolerated dose). To ensure complete inhibition of FLT3, all male subjects in both cohorts later received a starting dose of 135 mg/day quizartinib, and all females received a starting dose of 90 mg/day.
Participants by arm
| Arm | Count |
|---|---|
| Cohort 1; ≥60 Years of Age Participants ≥60 years of age who were relapsed after one first-line chemotherapy regimen (with or without consolidation) and after first complete remission \<12 months or are primary refractory to first-line chemotherapy received a starting dose of 200 mg/day quizartinib.
Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-)
After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day. | 157 |
| Cohort 2; ≥18 Years of Age Participants ≥18 years of age (including participants ≥60 years of age) who were relapsed or refractory after one second-line (salvage) regimen or after hematopoietic stem cell transplant (HSCT) received a starting dose of 200 mg/day quizartinib.
Exploratory: FLT3-ITD (+) and FLT3-ITD (-) Confirmatory: FLT3-ITD (+) and FLT3-ITD (-)
After an amendment, male participants received a starting dose of 135 mg/day quizartinib and all females received a starting dose of 90 mg/day. | 176 |
| Total | 333 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 0 |
| Overall Study | Still in follow up | 12 | 21 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Cohort 2; ≥18 Years of Age | Cohort 1; ≥60 Years of Age | Total |
|---|---|---|---|
| Age, Continuous | 51.0 years | 69.0 years | 63.0 years |
| Age, Customized At least 60 years | 44 Participants | 155 Participants | 199 Participants |
| Age, Customized Less than 60 years | 132 Participants | 2 Participants | 134 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 6 Participants | 4 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 150 Participants | 126 Participants | 276 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 20 Participants | 27 Participants | 47 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 5 Participants | 2 Participants | 7 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants | 5 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 6 Participants | 2 Participants | 8 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 12 Participants | 16 Participants |
| Race (NIH/OMB) White | 156 Participants | 135 Participants | 291 Participants |
| Region of Enrollment Canada | 2 participants | 2 participants | 4 participants |
| Region of Enrollment France | 29 participants | 24 participants | 53 participants |
| Region of Enrollment Germany | 27 participants | 37 participants | 64 participants |
| Region of Enrollment Italy | 12 participants | 16 participants | 28 participants |
| Region of Enrollment Netherlands | 5 participants | 5 participants | 10 participants |
| Region of Enrollment Poland | 0 participants | 2 participants | 2 participants |
| Region of Enrollment Spain | 8 participants | 5 participants | 13 participants |
| Region of Enrollment United Kingdom | 7 participants | 7 participants | 14 participants |
| Region of Enrollment United States | 86 participants | 59 participants | 145 participants |
| Sex: Female, Male Female | 83 Participants | 80 Participants | 163 Participants |
| Sex: Female, Male Male | 93 Participants | 77 Participants | 170 Participants |
| Weight | 74.76 kg STANDARD_DEVIATION 19.41 | 74.66 kg STANDARD_DEVIATION 14.75 | 74.72 kg STANDARD_DEVIATION 17.33 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 71 / 157 | 60 / 176 |
| other Total, other adverse events | 151 / 157 | 175 / 176 |
| serious Total, serious adverse events | 134 / 157 | 135 / 176 |
Outcome results
Primary
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants)
Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[-\] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.
Time frame: Within the first 3 cycles of treatment (84 days)
Population: Derived disease assessments were conducted in the Safety Population (FLT3-ITD \[-\] participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Complete remission with incomplete hematologic CRi | 13 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Complete remission with incomplete platelet (CRp) | 1 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Partial remission (PR) | 4 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | No response (NR) | 17 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Unknown | 7 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Composite complete remission (CRc) | 16 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Complete remission (CR) | 2 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Complete remission (CR) | 1 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Unknown | 6 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Complete remission with incomplete hematologic CRi | 10 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Complete remission with incomplete platelet (CRp) | 1 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Partial remission (PR) | 6 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | Composite complete remission (CRc) | 12 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [-] Participants) | No response (NR) | 16 participants |
Primary
Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants)
Derived disease assessment based on local morphology of bone marrow disease performed by each local site pathologist, including all on-treatment data (Safety Population, FLT3-ITD\[+\] Participants) Modified from Cheson et al, abbreviations include the following: CR=complete remission; CRc=composite complete remission (CR+CRp+CRi); CRi=complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia=all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib=All criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion; CRp=complete remission with incomplete platelet recovery; NR=no response; PR=partial remission.
Time frame: Within the first 3 cycles of treatment (84 days)
Population: Derived disease assessments were conducted in the Safety Population (FLT3-ITD \[+\] participants).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Composite complete remission (CRc) | 63 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Complete remission (CR) | 3 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Complete remission with incomplete platelet (CRp) | 4 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Complete remission with incomplete hematologic CRi | 56 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Unknown | 6 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Partial remission (PR) | 23 participants |
| Cohort 1; ≥60 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | No response (NR) | 20 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | No response (NR) | 24 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Composite complete remission (CRc) | 62 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Partial remission (PR) | 39 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Complete remission (CR) | 5 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Unknown | 11 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Complete remission with incomplete platelet (CRp) | 2 participants |
| Cohort 2; ≥18 Years of Age | Derived Disease Assessment Based on Local Morphology Including All On-Treatment Data (Safety Population, FLT3-ITD [+] Participants) | Complete remission with incomplete hematologic CRi | 55 participants |
Primary
Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status
CRc is defined as composite complete remission (CR+CRp+CRi) - CR = complete remission; CRp = complete remission with incomplete platelet recovery; CRi = complete remission with incomplete hematological recovery, includes participants who met CRia criteria plus participants who met CRib criteria; CRia = all criteria specified for CR are met except for incomplete hematological recovery with residual neutropenia \<1 x 10\^9/L with or without complete platelet recovery. Red blood cell and platelet transfusion independence is not required; CRib = all criteria for CR or CRp are met, except for recent red blood cell or platelet transfusion.
Time frame: within 28 months
Population: Composite complete remission was assessed in the Safety Population.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Cohort 1; ≥60 Years of Age | Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status | FLT3-ITD(+) | 63 participants |
| Cohort 1; ≥60 Years of Age | Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status | FLT3-ITD(-) | 16 participants |
| Cohort 2; ≥18 Years of Age | Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status | FLT3-ITD(+) | 62 participants |
| Cohort 2; ≥18 Years of Age | Number of Participants With Composite Complete Remission (CRc), Categorised by FLT3-ITD Status | FLT3-ITD(-) | 12 participants |
Secondary
Duration of Any Response in FLT3-ITD (-) Participants
Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).
Time frame: From the time of any response until disease progression or death, up to approximately 3 years post treatment
Population: Response (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[-\] participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Duration of Any Response in FLT3-ITD (-) Participants | 22.4 weeks |
| Cohort 2; ≥18 Years of Age | Duration of Any Response in FLT3-ITD (-) Participants | 8.1 weeks |
Secondary
Duration of Any Response in FLT3-ITD (+) Participants
Kaplan-Meier analysis of duration of any response (CR, CRp, CRi, or PR), derived based on local morphology for participants who achieved a response during the first 3 cycles of treatment (Safety Population).
Time frame: From the time of any response until disease progression or death, up to approximately 3 years post treatment
Population: Response (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[+\] participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Duration of Any Response in FLT3-ITD (+) Participants | 15.7 weeks |
| Cohort 2; ≥18 Years of Age | Duration of Any Response in FLT3-ITD (+) Participants | 14.1 weeks |
Secondary
Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data
Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of \>1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.
Time frame: From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment
Population: Duration of composite complete remission was assessed in the Safety Population based on FLT3-ITD (-) participants available for this analysis (Cohort 1: n=16; Cohort 2: n=12).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data | 16.4 weeks |
| Cohort 2; ≥18 Years of Age | Duration of Composite Complete Remission in FLT3-ITD (-) Participants Who Achieved CRc Based on All On-Treatment Data | 7.0 weeks |
Secondary
Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data
Kaplan-Meier analysis of duration of composite complete remission derived based on local morphology including all on-treatment data (Safety Population). The definition of relapse at CRc includes an evaluation of blasts in the peripheral blood of \>1%.Though not specified in the protocol, the addition of these criteria was deemed necessary for consistency with the Cheson criteria.
Time frame: From time at which CRc was achieved until disease progression or death, up to approximately 3 years post treatment
Population: Duration of composite complete remission was assessed in the Safety Population based on FLT3-ITD (+) participants available for this analysis (Cohort 1: n=63; Cohort 2: n=62).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data | 12.1 weeks |
| Cohort 2; ≥18 Years of Age | Duration of Composite Complete Remission in FLT3-ITD (+) Participants Who Achieved CRc Based on All On-Treatment Data | 10.6 weeks |
Secondary
Early Treatment-related Death
Early treatment-related deaths included all treatment-related deaths prior to the end of Cycle 3 with a 3-day window (Cycle 3 end date + 3 days), unless the death was following a CRc response assessed by the Investigator.
Time frame: Within first 3 cycles of treatment (84 days)
Population: Early treatment-related deaths were assessed in the Safety Population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Early Treatment-related Death | 4 participants |
| Cohort 2; ≥18 Years of Age | Early Treatment-related Death | 4 participants |
Secondary
Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants
Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).
Time frame: From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment
Population: Leukemia-free survival (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[-\] participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants | 16.4 weeks |
| Cohort 2; ≥18 Years of Age | Median Duration of Leukemia-free Survival in FLT3-ITD (-) Participants | 7.0 weeks |
Secondary
Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants
Kaplan-Meier analysis of leukemia-free survival in participants who achieved a CRc in the first three cycles of treatment derived based on local morphology (Safety Population).
Time frame: From the time CRc was achieved until disease progression or death, up to approximately 3 years post treatment
Population: Leukemia-free survival (based on local morphology) was assessed in the Safety Population (FLT3-ITD \[+\] participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants | 12.1 weeks |
| Cohort 2; ≥18 Years of Age | Median Duration of Leukemia-free Survival in FLT3-ITD (+) Participants | 12.9 weeks |
Secondary
Median Duration of Overall Survival in FLT3-ITD (-) Participants
Kaplan-Meier analysis of overall survival (Safety Population)
Time frame: Time from first dose to death from any cause, up to approximately 3 years post treatment
Population: Overall survival was assessed in the Safety Population (FLT3-ITD \[-\] participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Median Duration of Overall Survival in FLT3-ITD (-) Participants | 19.1 weeks |
| Cohort 2; ≥18 Years of Age | Median Duration of Overall Survival in FLT3-ITD (-) Participants | 25.1 weeks |
Secondary
Median Duration of Overall Survival in FLT3-ITD (+) Participants
Kaplan-Meier analysis of overall survival (Safety Population)
Time frame: Time from first dose to death from any cause, up to 3 years post treatment
Population: Overall survival was assessed in the Safety Population (FLT3-ITD \[+\] participants).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort 1; ≥60 Years of Age | Median Duration of Overall Survival in FLT3-ITD (+) Participants | 25.4 weeks |
| Cohort 2; ≥18 Years of Age | Median Duration of Overall Survival in FLT3-ITD (+) Participants | 24.0 weeks |