A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.

Astellas Pharma Inc97 enrolled

Overview

The purpose of phase 1 part in this study was to determine the maximum tolerated dose (MTD) and/or recommended expansion dose (RED) of ASP2215 concomitant with cytarabine/idarubicin as induction chemotherapy based on the status of the onset of dose-limiting toxicity (DLT) in newly diagnosed Acute Myeloid Leukemia (AML) subjects. Phase 1 part also evaluated safety and tolerability and characterized the pharmacokinetic (PK) parameters of ASP2215 concomitant with induction and consolidation chemotherapy as well as evaluated the PK parameters of cytarabine concomitant with ASP2215. The purpose of phase 2 part was to evaluate efficacy of ASP2215 in combination with induction therapy. Phase 2 cohort also evaluated safety and characterized the PK parameters of ASP2215 in combination with induction and consolidation therapy followed by maintenance therapy in newly diagnosed FLT3-mutated AML subjects.

This study was composed of Phase 1 part (the dose-evaluation part and the expansion part) and Phase 2 part. In the dose-evaluation part of Phase 1 part, at least 3 subjects received ASP2215 at each dose (low, middle, and high) for determination of MTD and/or RED. Treatment of AML in Phase 1 part was composed of 3 periods of therapy: remission induction, consolidation, and maintenance. The decision of whether or not to proceed to the next dose was made based on the occurrence of DLT during Cycle 1 of the induction period. In the expansion part of Phase 1 part, a maximum of 3 subjects received ASP2215 at RED that had been recommended in the dose-evaluation part and the safety was assessed based on the onset of DLTs during Cycle 1 of the induction and consolidation periods. In Phase 2 part, Subjects received ASP2215 at the recommended dose established in Phase 1 part. The target population was limited to newly diagnosed FLT3-mutated AML.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Interventions

GilteritinibDRUG

Once-daily oral administration on 14 consecutive days in every cycle in each period.

IdarubicinDRUG

Induction period: Once-daily intravenous injection of 12 mg/m\^2 idarubicin on 3 consecutive days.

CytarabineDRUG

Induction period: Once-daily intravenous injection of 100 mg/m\^2 cytarabine on 7 consecutive days. Consolidation period: Twice-daily intravenous injection of 1.5 g/m\^2 cytarabine on Days 1, 3, and 5.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 69 Years

Medical Language ↔ Plain English

Inclusion Criteria: \[Phase 1 part\] * Subject is defined as having previously untreated de novo AML according to the World Health Organization (WHO) criteria (2008) within 28 days prior to study enrollment. * Subject has an Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2. * Subject must meet all of the following criteria in the laboratory test at screening: * Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels of ≤ 2.5 × institutional upper limit of normal (ULN) * Total serum bilirubin level of ≤ 1.5 × institutional ULN * Serum creatinine level of ≤ 1.5 × institutional ULN or an estimated glomerular filtration rate (eGFR) of \> 50 mL/min * Subject is suitable for oral administration of ASP2215. * Female subject falls under the following: * Of non-childbearing potential: * ・Post-menopausal (defined as at least 1 year with no menses without a medical reason such as drug administration) at screening, or * ・Documented surgically sterile or status post-hysterectomy (at least 1 month prior to screening) * Of childbearing potential: * ・Has a negative result for the pregnancy test at screening, and * ・Agrees to use an appropriate contraception starting at screening and throughout the study period and for 60 days after the final study drug administration * Female subject agrees not to breastfeed starting at screening and throughout the study period and for 60 days after the final study drug administration. * Female subject agrees not to donate ova starting at screening and throughout the study period and for 60 days after the final study drug administration. * Male subject and his female spouse/partner who is of childbearing potential agrees to use an appropriate contraception starting at screening and throughout the study period and for 120 days after the final study drug administration. * Male subject agrees not to donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration. * Subject agrees not to participate in another interventional study while on study treatment. * Subject can be admitted during the induction period. \[Phase 2 part\] * Subject has a diagnosis of previously-untreated de novo acute myeloid leukemia (AML) according to World Health Organization (WHO) classification (2017) documented within 28 days prior to enrollment. * Subject is positive for FLT3-ITD and/or TKD mutation in bone marrow or whole blood as determined by the central lab. Registration by the local lab result is not acceptable. * Subject has an ECOG performance status (PS) 0 to 1. Subject who has an ECOG PS 2 is eligible only if the primary disease related symptoms such as pneumonia and febrile neutropenia are the cause of PS score. * Subject is suitable for oral administration of ASP2215. * Female subject is not pregnant and at least 1 of the following conditions apply: * Not a woman of childbearing potential (WOCBP) * WOCBP who agrees to follow the contraceptive guidance from the time of informed consent through at least 180 days after final study treatment administration. * Female subject must agree not to breastfeed starting at screening and throughout the study period, and for 60 days after the final study drug administration. * Female subject must not donate ova starting at screening and throughout the study period, and for 180 days after the final study drug administration. * Male subject and their female partners who are of childbearing potential must be using highly effective contraception per locally accepted standards in addition to a barrier method starting at screening and continue throughout the study period and for 120 days after the final study drug administration. * Male subject must not donate sperm starting at screening and throughout the study period and for 120 days after the final study drug administration. * Male subject with pregnant partner(s) must agree to remain abstinent or use a condom for the duration of the pregnancy throughout the study period and for 120 days after the final study treatment administration. * Subject agrees not to participate in another interventional study while on treatment. * Subject must meet the following criteria as indicated on the clinical laboratory tests: * Serum creatinine ≤ 1.5 × institutional upper limit of normal (ULN), or if serum creatinine outside normal range, then glomerular filtration rate (GFR) \> 50 mL/min/1.73m\^2 as calculated with the 4-parameter Modification of Diet in Renal Disease (MDRD) equation. * Serum total bilirubin ≤ 2.5 mg/dL (43 μmol/L), except for subjects with Gilbert's syndrome. * Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 3 x ULN. If liver abnormality by the primary disease is suspected, subject may be pre-registered to initiate the chemotherapy. Prior to registration, AST/ALT values must meet the criteria to continue the study. * Serum magnesium ≥ institutional lower limit of normal (LLN). Subject may pre-register without magnesium value, but subject must meet the criteria prior to the full registration on Day 8. * Serum potassium ≥ institutional lower limit of normal (LLN). Exclusion Criteria: \[Phase 1 part\] * Subject was diagnosed with acute promyelocytic leukemia (APL). * Subject has breakpoint cluster region-abelson (BCR-ABL)-positive leukemia (chronic myelogenous leukemia in blast crisis). * Subject has active malignant tumors other than AML or myelodysplastic syndrome (MDS). * Subject has received prior AML treatment except for the following: * Urgent leukapheresis * Hydroxyurea administration for emergency treatment of hyperleukocytosis (≤ 7 days) * Administration of retinoic acid before the diagnosis to exclude APL (≤ 7 days) * Supportive care using growth factors or cytokines * Steroid administration to treat hypersensitivity or blood transfusion reactions * Subject has clinically active central nervous system leukemia. * Subject has disseminated intravascular coagulation (DIC). * Subject has had major surgery within 28 days prior to the first study drug administration. * Subject has had radiation therapy within 28 days prior to the first study drug administration. * Subject has congestive heart failure of New York Heart Association (NYHA) class 3 or 4, or subject with a past history of congestive heart failure of NYHA class 3 or 4 and in whom echocardiogram (ECHO) or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of \< 45%. * Subject has cardiac impairment or a clinically significant cardiac disease, including any one of the following: * Complete left bundle branch block * Obligate use of a cardiac pacemaker * Long QT syndrome at Screening * Prolongation of the QTc interval (\> 450 ms) on electrocardiogram (ECG) at screening * Right bundle branch block + left anterior hemiblock (bifascicular block) * Angina pectoris within 3 months prior to study drug administration * Acute myocardial infarction within 3 months prior to study drug administration * Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A. * Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject. * Subject requires treatment with concomitant drugs that target serotonin 5HT1 or 5HT2B receptors or sigma receptors, with the exception of drugs that are considered absolutely essential for treatment of the subject. * Subject has an active uncontrollable infection. * Subject is known to have human immunodeficiency virus (HIV) infection. * Subject has active hepatitis B or C or other active hepatic disorders. * Subject has any condition that, in the investigator's or sub-investigator's opinion, makes the subject unsuitable for study participation. * Potassium and magnesium levels of below institutional lower limit of normal in the laboratory test at screening. \[Phase 2 part\] * Subject was diagnosed with acute promyelocytic leukemia (APL). * Subject has known BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis). * Subject has therapy-related AML. * Subject has active malignant tumors other than AML. * Subject has received previous therapy for AML, with the exception of the following: * Emergency leukapheresis * Emergency treatment for hyperleukocytosis with hydroxyurea for ≤ 10 days * Preemptive treatment with retinoic acid prior to exclusion of APL ≤ 7 days * Growth factor or cytokine support * Steroids for the treatment of hypersensitivity or transfusion reactions. * Subject has QTcF interval \> 450 ms (average of triplicate determinations based on central reading). * Subject with long QT syndrome. * Subject has clinically active central nervous system leukemia. * Subject has had major surgery within 4 weeks prior to the first study dose. * Subject has radiation therapy within 4 weeks prior to the first study dose. * Subject has immediate life-threatening, severe complications of leukemia such as severe uncontrolled bleeding and/or severe disseminated intravascular coagulation * Subject is known to have human immunodeficiency virus infection. * Subject has active hepatitis B or C. * Subject has an uncontrolled infection. An infection controlled with an approved or closely monitored antibiotic/antiviral/antifungal treatment is allowed. * Subject has uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia, congestive heart failure New York Heart Association (NYHA) class 3 or 4 or subject has a history of congestive heart failure of NYHA class 3 or 4 and echocardiogram (ECHO) or Multiple Gate Acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a left ventricular ejection fraction (LVEF) of \< 45%. * Subject requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP) 3A. * Subject requires treatment with concomitant drugs that target serotonin 5HT2B receptors or sigma nonspecific receptors, with the exception of drugs that are considered absolutely essential for treatment of the subject. * Subject requires treatment with concomitant drugs that are strong inhibitors or inducers of P glycoprotein (P-gp) with the exception of drugs that are considered absolutely essential for the care of the subject. * Subject has prior malignancies, except resected basal cell carcinoma or treated cervical carcinoma in situ. Cancer treated with curative intent ≥ 5 years previously will be allowed. Cancer treated with curative intent \< 5 years previously will not be allowed. * Subject has any condition which makes the subject unsuitable for study participation.

Locations (55)

Site JP81037

Anjo, Aichi-ken, Japan

Site JP00003

Nagoya, Aichi-ken, Japan

Site JP81003

Nagoya, Aichi-ken, Japan

Site JP81027

Nagoya, Aichi-ken, Japan

Site JP81038

Toyohashi, Aichi-ken, Japan

Site JP81010

Narita, Chiba, Japan

Outcomes

Primary Outcomes

Phase 1 Part: Maximum Tolerated Dose (MTD) of Gilteritinib

The MTD was defined as the highest dose of gilteritinib at which the posterior mean of the DLT incidence during Cycle 1 of induction therapy was estimated to be closest to 33%.

Time frame: Day 1 up to the end of Induction period cycle 1 (up to 42 days)

Phase 1 Part: Recommended Expansion Dose (RED) of Gilteritinib

RED was the recommended dose used in Phase 2 of the study that was decided by the sponsor's responsible person by comprehensively assessing the data obtained from the study.

Time frame: Day 1 up to the end of Induction period cycle 1 (up to 42 days)

Phase 1 Part: Number of Participants With Dose Limiting Toxicities (DLTs) of Gilteritinib

DLTs were defined as: Any Grade ≥ 3 non-hematologic or extramedullary toxicity with the following exceptions: * Anorexia or fatigue * Grade 3 nausea and/or vomiting if participant did not require tube feeding or total parenteral nutrition, or diarrhea if the events did not require or prolong hospitalization that could be managed to grade ≤ 2 with standard antiemetic or antidiarrheal medications used at prescribed dose within 7 days of onset. * Grade 3 mucositis that resolved to Grade ≤ 2 within 7 days of onset, fever with neutropenia, with or without infection, infection * Grade 4 peripheral neutrophil count \< 500/cubic millimeters (mm\^3) * Platelet count \< 20,000/mm\^3 due to bone marrow hypoplasia * Grade ≥ 3 platelet count \< 50,000/mm\^3 accompanying bleeding * Grade 4 platelet count \< 25,000/mm\^3 requiring platelet transfusion DLT was assessed until cycle 1 of dose evaluation induction period and until cycle 1 of dose expansion consolidation period.

Time frame: Day 1 up to the end of Consolidation Cycle 1 (approximately up to 4 months)

Phase 1 Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE included both serious and non-serious AEs. TEAE for Phase 1 was defined as an AE observed after the date of first dose until 30 days after the last dose.

Time frame: From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.1 years)

Phase 2 Part: Complete Remission (CR) Rate: Induction Period

Percentage of participants with CR was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm3 and platelet count of ≥ 100,000/mm3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%.

Time frame: From the date of first dose up to the start of Consolidation (approximately up to 4 months)

Secondary Outcomes

Phase 1 Part: Maximum Concentration (Cmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

Cmax was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Time frame: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

Phase 1 Part: Time to Attain Cmax (Tmax) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

Tmax was derived from the PK samples collected.

Time frame: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

Phase 1 Part: Area Under Plasma Concentration-time Curve From Time 0 to 24 (AUC24) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

AUC24 was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Time frame: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

Phase 1 Part: Area Under The Concentration-Time Curve From The Time Zero to The Last Measurable Concentration (AUClast) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

AUClast was derived from the PK samples collected. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Time frame: Induction period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 4 Consolidation period: Pre-dose, 1, 2, 4, 6, 10, and 24 hours post-dose on Cycle 1 Day 1

Phase 1 Part: Plasma Trough Concentration (Ctrough) of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

Ctrough is the plasma concentration prior to drug administration. It was planned that standard deviation(SD) would only be calculated if there are more than 3 participants analyzed otherwise, SD was not calculated.

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Site JP81039

Matsuyama, Ehime, Japan

Site JP81007

Yoshida-gun, Fukui, Japan

Site JP00002

Maebashi, Gunma, Japan

Site JP81001

Maebashi, Gunma, Japan

...and 45 more locations

Time frame: Induction period: Pre-dose on Cycle 1 Day 8, 11, and 17 Consolidation period: Pre-dose on Cycle 1 Day 6 and 15

Phase 1 Part: Plasma Trough Concentration of Cytarabine Concomitant With Gilteritinib With Induction and Consolidation Period

Time frame: Induction period: Predose on Cycle 1 Day 1, 3, and 8 Consolidation period: Predose on Cycle 1 Day 2 and 6

Phase 2 Part: Plasma Trough Concentration of Gilteritinib Concomitant With Induction and Consolidation Chemotherapy

Ctrough is the plasma concentration prior to drug administration.

Time frame: Induction period : Predose on Cycle 1 Day 15 and 21 Consolidation period: Predose on Cycle 1 Day 8 and 15

Phase 2 Part: Overall Survival (OS)

Overall survival (OS) was defined as the time from the date of first dose of day 1 to the date of death due to any cause. Participants still alive or lost to follow up was censored at the time they were last known to be alive. Kaplan-Meier (KM) estimate was used for analysis.

Time frame: From the date of first dose up to the date of death (maximum duration: approximately 4.4 years)

Phase 2 Part: Event Free Survival (EFS)

Event-free survival (EFS): time from date of first dose of study regimen until date of documented relapse, treatment failure or death from any cause, whichever occurred first. KM estimate was used for analysis. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in bone marrow aspirate (BMA)/reappearance of significant numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%. Treatment failure: participants who failed to achieve composite complete remission (CRc) or who discontinued treatment due to "lack of efficacy" without previous response. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi). CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (\< 100,000/mm\^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (\< 1,000/mm\^3). CR: defined in outcome measure #5.

Time frame: From the date of first dose up to the date of documented relapse, treatment failure or death from any cause (maximum duration: approximately 4.4 years)

Phase 2 Part: Relapse Free Survival (RFS)

Relapse-free survival (RFS): time from date of achievement of first CRc until relapse or death from any cause. KM estimate was used for analysis. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in bone marrow aspirate (BMA)/reappearance of significant numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi). CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (\< 100,000/mm\^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (\< 1,000/mm\^3). CR: morphologically leukemia-free state at post-baseline visit, having neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods \& extramedullary leukemia. Blast counts in peripheral blood was ≤ 2%.

Time frame: From the date of achievement of first CRc up to the date of documented relapse or death from any cause (maximum duration: approximately 3.9 years)

Phase 2 Part: CR Rate After Consolidation and Maintenance Period

Percentage of participants with CR was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the consolidation period refers to the best response from the start of treatment in the induction period until the end of the consolidation period and for the maintenance period refers to the best response from the start of treatment in the induction period until the end of the maintenance period.

Time frame: CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

Phase 2 Part: CR Rate Without Minimal Residual Disease (MRD) After Each Treatment Therapy Period

CR% without MRD reported. CR rate without MRD after each treatment therapy was defined similarly as CR rate after each treatment therapy. Responders achieve that the best response is CR and MRD status was negative. CR was defined as a morphologically leukemia-free state, having a neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods and extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

Time frame: IP: From date of first dose up to end of period (approximately 1.4 years), CP: From date of first dose up to end of period (approximately 1.8 years), MP: From date of first dose up to the end of period (approximately 3.8 years)

Phase 2 Part: CR With Partial Hematological Recovery (CRh) Rate After Each Treatment Therapy Period

Percentage of participants with CRh was reported. CRh was defined as a condition at the post baseline visit, having bone marrow blasts \< 5%, partial hematologic recovery neutrophil count≥ 500/mm\^3 and platelet count ≥ 50,000/mm\^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

Phase 2 Part: Composite CR (CRc) Rate After Each Treatment Therapy Period

Percentage of participants with CRc reported. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recovery (CRi). CRp: met all CR criteria, except unrecovered platelet count (\< 100,000/mm\^3). CRi: met all CR criteria, except unrecovered neutrophil count (\< 1,000/mm\^3). CR: morphologically leukemia-free state, having neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods \& extramedullary leukemia. Blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

Phase 2 Part: CR/CRh Rate After Each Treatment Therapy Period

Percentage of participants with CR/CRh was reported. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. CRh was defined as a condition at the post baseline visit, having bone marrow blasts \< 5%, partial hematologic recovery neutrophil count≥ 500/mm\^3 and platelet count ≥ 50,000/mm\^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. Derived response assessment after the IP refers to the best response from the start of treatment in the IP until the end of the IP, after CP refers to the best response from the start of treatment in the IP until the end of the CP and for the MP refers to the best response from the start of treatment in the IP until the end of the MP.

Phase 2 Part: Duration of CR

Duration of CR was defined as the time from the date of achieving first CR until the date of first documented relapse for participants who achieved CR. KM estimate was used for analysis. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%.

Time frame: From the date of achieving CR up to the date of documented relapse (maximum duration: approximately 2.6 years)

Phase 2 Part: Duration of CR/CRh

Duration of CR/CRh is defined as the time from the date of achieving first CR/CRh until the date of first documented relapse for participants who achieved CR/CRh. KM estimate was used for analysis. CR was defined as a morphologically leukemia-free state at the post-baseline visit, having a neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods and no evidence of extramedullary leukemia. The blast counts in peripheral blood was ≤ 2%. CRh was defined as a condition at the post baseline visit, having bone marrow blasts \< 5%, partial hematologic recovery neutrophil count≥ 500/mm\^3 and platelet count ≥ 50,000/mm\^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%.

Time frame: From the date of achieving CR/CRh up to the date of documented relapse (maximum duration: approximately 2.6 years)

Phase 2 Part: Duration of CRh

Duration of CRh was defined as the time from date of achieving first CRh until date of first documented relapse for participants who achieved CRh. KM estimate was used for analysis. CRh was defined as a condition at the post baseline visit, having bone marrow blasts \< 5%, partial hematologic recovery neutrophil count≥ 500/mm\^3 and platelet count ≥ 50,000/mm\^3, no evidence of extramedullary leukemia and could be classified as CR. The blast counts in peripheral blood was ≤ 2%. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%.

Time frame: From the date of achieving CRh up to the date of documented relapse (maximum duration: approximately 2.6 years)

Phase 2 Part: Duration of CRc

Duration of CRc is defined as the time from the date of achieving first CRc until the date of first documented relapse for participants who achieved CRc. KM estimate was used for analysis. CRc: rate of all complete \& incomplete remissions i.e. CR + CR with incomplete platelet recovery (CRp) + CR with incomplete hematological recover (CRi). CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (\< 100,000/mm\^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (\< 1,000/mm\^3). CR: morphologically leukemia-free state at post-baseline visit, having neutrophil count of ≥ 1,000/mm\^3 and platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods \& extramedullary leukemia. Blast counts in peripheral blood was ≤ 2%. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%.

Time frame: From the date of achieving CRc up to the date of documented relapse (maximum duration: approximately 2.7 years)

Phase 2 Part: Duration of Response (DoR)

DoR: from first day of achieving CRc (CR+ CRp,+CRi)/partial remission (PR) to first day of relapse. KM estimate was used for analysis. CR: morphologically leukemia-free state at post-baseline visit, having neutrophil count of ≥ 1,000/mm\^3 \& platelet count of ≥ 100,000/mm\^3, bone marrow blasts \< 5%. No evidence of Auer rods \& extramedullary leukemia. Peripheral blood blast counts was ≤ 2%. CRp: met all CR criteria at post-baseline visit, except unrecovered platelet count (\< 100,000/mm\^3). CRi: met all CR criteria at post-baseline visit, except unrecovered neutrophil count (\< 1,000/mm\^3). PR: condition with regeneration of normal hematopoietic cells in bone marrow, no detectable blasts, ≥ 50% decrease of blasts in BMA \& total bone marrow blasts of 5-25%. No evidence of extramedullary leukemia. Relapse: reappearance of leukemic blasts in peripheral blood (\>2%)/≥ 5% blasts in BMA/reappearance of numbers of peripheral blasts and an increase in percentage of blasts in BMA to \> 25%

Time frame: From the date of achieving CR, CRp, CRi/PR up to the date of documented relapse (maximum duration: approximately 2.7 years)

Phase 2 Part: Number of Participants With Treatment Emergent Adverse Events (TEAEs)

An AE was defined as any untoward medical occurrence in a participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. An AE could therefore be any unfavorable \& unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a medicinal product. TEAE for Phase 2 was defined as an AE observed after the date of first dose until 30 days after the last dose. TEAE included both serious and non-serious AEs.

Time frame: From the date of first dose up to 30 days after the last dose ( maximum duration up to approximately 4.4 years)

A Study of ASP2215 in Combination With Induction and Consolidation Chemotherapy in Patients With Newly Diagnosed Acute Myeloid Leukemia.

Overview

Conditions

Interventions

Eligibility

Locations (55)

Outcomes

Primary Outcomes

Secondary Outcomes