Acute Myeloid Leukemia Clinical Trial
A Study of ASP2215 Versus Salvage Chemotherapy in Patients With Relapsed or Refractory Acute Myeloid Leukemia (AML) With FMS-like Tyrosine Kinase (FLT3) Mutation
The purpose of this study is to determine the clinical benefit of ASP2215 therapy in participants with FMS-like tyrosine kinase (FLT3) mutated acute myeloid leukemia (AML) who are refractory to or have relapsed after first-line AML therapy as shown with overall survival (OS) compared to salvage chemotherapy, and to determine the efficacy of ASP2215 therapy as assessed by the rate of complete remission and complete remission with partial hematological recovery (CR/CRh) in these participants.
This study will also determine the overall efficacy in event-free survival (EFS) and complete remission (CR) rate of ASP2215 compared to salvage chemotherapy.
Participants considered an adult according to local regulations at the time of signing informed consent may participate in this study. Participants will be randomized in a 2:1 ratio to receive ASP2215 or salvage chemotherapy. Participants will enter the screening period up to 14 days prior to the start of treatment. Prior to randomization, a salvage chemotherapy regimen will be pre-selected for each participant; options will include low-dose cytarabine (LoDAC), azacitidine, mitoxantrone, etoposide, and intermediate-dose cytarabine (MEC), or fludarabine, cytarabine, and granulocyte colony-stimulating factor (G-CSF) with idarubicin (FLAG-IDA). The randomization will be stratified by response to first-line therapy and pre-selected salvage chemotherapy. Participants will be administered treatment over continuous 28-day cycles.
After treatment discontinuation, participants will have a pre-hematopoietic stem cell transplant (HSCT)/end-of-treatment visit within 7 days after treatment discontinuation, followed by a 30-day follow-up for safety, in which a telephone contact with the participant is sufficient unless any assessment must be repeated for resolution of treatment-related adverse events (AEs). After that, long term follow-up will be done every 3 months up to 3 years from the participant's end-of-treatment visit.
Participant has a diagnosis of primary acute myeloid leukemia (AML) or AML secondary to myelodysplastic syndrome (MDS) according to WHO classification (2008) as determined by pathology review at the treating institute.
Participant is refractory to or relapsed after first-line AML therapy (with or without hematopoietic stem cell transplant (HSCT)).
Refractory to first-line AML therapy is defined as:
1. Participant did not achieve complete remission/complete remission with incomplete hematologic recovery/complete remission with incomplete platelet recovery (CR/CRi/CRp) under initial therapy. A Participant eligible for standard therapy must receive at least one cycle of an anthracycline containing induction block in standard dose for the selected induction regimen. A Participant not eligible for standard therapy must have received at least one complete block of induction therapy seen as the optimum choice of therapy to induce remission for this subject.
Untreated first hematologic relapse is defined as:
Participant must have achieved a CR/CRi/CRp (criteria as defined by [Cheson et al, 2003], see Section 5.3) with first line treatment and has hematologic relapse.
Participant is positive for FLT3 mutation in bone marrow or whole blood as determined by the central lab. A Participant with rapidly proliferative disease and unable to wait for the central lab results can be enrolled based on a local test performed after completion of the last interventional treatment. Participants can be enrolled from a local test result if they have any of the following FLT3 mutations: FLT3 internal tandem duplication (ITD), FLT3 tyrosine kinase domain (TKD)/D835 or FLT3- TKD/I836.
Participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
Participant is eligible for pre-selected salvage chemotherapy.
Participant must meet the following criteria as indicated on the clinical laboratory tests:
Serum aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x upper limit of normal (ULN)
Serum total bilirubin ≤ 1.5 x ULN
Serum creatinine ≤ 1.5 x ULN or an estimated glomerular filtration rate of > 50 mL/min as calculated by the Modification of Diet in Renal Disease equation.
Participant is suitable for oral administration of study drug.
Female Participant must either:
Be of non-child bearing potential:
post-menopausal (defined as at least 1 year without any menses) prior to Screening, or
documented as surgically sterile (at least 1 month prior to Screening)
Or, if of childbearing potential,
Agree not to try to become pregnant during the study and for 180 days after the final study administration
And have a negative urine pregnancy test at Screening
And, if heterosexually active, agree to consistently use highly effective contraception per locally accepted standards in addition to a barrier method starting at Screening and throughout the study period and for 180 days after the final study drug administration.
Female Participant must agree not to breastfeed at Screening and throughout the study period and for 60 days after the final study drug administration.
Female Participant must not donate ova starting at Screening and throughout the study period and for 180 days after the final study drug administration.
Male Participant 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 Participant must not donate sperm starting at Screening and throughout the study period and 120 days after the final study drug administration.
Participant agrees not to participate in another interventional study while on treatment.
Participant was diagnosed as acute promyelocytic leukemia (APL).
Participant has BCR-ABL-positive leukemia (chronic myelogenous leukemia in blast crisis).
Participant has AML secondary to prior chemotherapy for other neoplasms (except for MDS).
Participant is in second or later hematologic relapse or has received salvage therapy for refractory disease
Participant has clinically active central nervous system leukemia.
Participant has been diagnosed with another malignancy, unless disease-free for at least 5 years. Participants with treated nonmelanoma skin cancer, in situ carcinoma or cervical intraepithelial neoplasia, regardless of the disease-free duration, are eligible for this study if definitive treatment for the condition has been completed. Participants with organ-confined prostate cancer with no evidence of recurrent or progressive disease are eligible if hormonal therapy has been initiated or the malignancy has been surgically removed or treated with definitive radiotherapy.
Participant has received prior treatment with ASP2215 or other FLT3 inhibitors (with the exception of sorafenib and midostaurin used in first-line therapy regimen as part of induction, consolidation, and/or maintenance).
Participant has clinically significant abnormality of coagulation profile, such as disseminated intravascular coagulation (DIC).
Participant has had major surgery within 4 weeks prior to the first study dose.
Participant has radiation therapy within 4 weeks prior to the first study dose.
Participant has congestive heart failure New York Heart Association (NYHA) class 3 or 4, or Participant with a history of congestive heart failure NYHA class 3 or 4 in the past, unless a screening echocardiogram performed within 3 months prior to study entry results in a left ventricular ejection fraction that is ≥ 45%.
Participant requires treatment with concomitant drugs that are strong inducers of cytochrome P450 (CYP)3A.
Participants with mean of triplicate Fridericia-corrected QT interval (QTcF) > 450 ms at Screening based on central reading.
Participants with Long QT Syndrome at Screening.
Participants with hypokalemia and hypomagnesemia at Screening (defined as values below lower limit of normal [LLN]).
Participant 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.
Participant requires treatment with concomitant drugs that target serotonin 5-hydroxytryptamine receptor 1 (5HT1R) or 5-hydroxytryptamine receptor 2B (5HT2BR) or sigma nonspecific receptor with the exception of drugs that are considered absolutely essential for the care of the subject.
Participant has an active uncontrolled infection.
Participant is known to have human immunodeficiency virus infection.
Participant has active hepatitis B or C, or other active hepatic disorder.
Participant has any condition which makes the Participant unsuitable for study participation.
Participant has active clinically significant GVHD or is on treatment with systemic corticosteroids for GVHD.
Participant has an FLT3 mutation other than the following: FLT3-ITD, FLT3-TKD/D835 or FLT3-TKD/I836.
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There are 100 Locations for this study
Birmingham Alabama, 35294, United States
Los Angeles California, 90095, United States
Orange California, 92868, United States
San Francisco California, 94143, United States
New Haven Connecticut, 06504, United States
Gainesville Florida, 32610, United States
Atlanta Georgia, 30342, United States
Chicago Illinois, 60637, United States
Westwood Kansas, 66205, United States
Louisville Kentucky, 40202, United States
New Orleans Louisiana, 70112, United States
Baltimore Maryland, 21201, United States
Boston Massachusetts, 02114, United States
Boston Massachusetts, 02215, United States
Boston Massachusetts, 02215, United States
Detroit Michigan, 48201, United States
Minneapolis Minnesota, 55455, United States
Lebanon New Hampshire, 03756, United States
Hackensack New Jersey, 07601, United States
New Brunswick New Jersey, 08903, United States
Buffalo New York, 14263, United States
New York New York, 10029, United States
New York New York, 10032, United States
New York New York, 10065, United States
New York New York, 10065, United States
Syracuse New York, 13210, United States
Durham North Carolina, 27710, United States
Winston-Salem North Carolina, 27157, United States
Cleveland Ohio, 44106, United States
Columbus Ohio, 43210, United States
Oklahoma City Oklahoma, 73104, United States
Hershey Pennsylvania, 17033, United States
Philadelphia Pennsylvania, 19104, United States
Philadelphia Pennsylvania, 19107, United States
Charleston South Carolina, 29425, United States
Nashville Tennessee, 37232, United States
Milwaukee Wisconsin, 53226, United States
Yvoir , 5530, Belgium
Edmonton Alberta, T6G 2, Canada
Hamilton Ontario, L8V 1, Canada
Toronto Ontario, M5G 2, Canada
Montreal Quebec, H1T 2, Canada
Brest , 29609, France
Le Chesnay Cedex , 78157, France
Lille , 59037, France
Pessac , 33604, France
Rennes , 35033, France
Toulouse , 31059, France
Dresden , 01307, Germany
Leipzig , 04103, Germany
Marburg , 35043, Germany
Munchen , 81737, Germany
Tubingen , 72076, Germany
Ashkelon , 78278, Israel
Haifa , 31096, Israel
Jerusalem , 91031, Israel
Jerusalem , 91120, Israel
Petah Tikva , 49100, Israel
Rehovot , 76100, Israel
Bologna , 40138, Italy
Brescia , 25126, Italy
Milan , 20132, Italy
Palermo , 90146, Italy
Pavia , 27100, Italy
Roma , 00189, Italy
Varese , 21100, Italy
Nagoya Aichi, , Japan
Narita Chiba, , Japan
Yoshida-gun Fukui, , Japan
Sapporo Hokkaido, , Japan
Kobe Hyogo, , Japan
Tsukuba Ibaraki, , Japan
Isehara Kanagawa, , Japan
Yokohama Kanagawa, , Japan
Sendai Miyagi, , Japan
Kurashiki Okayama, , Japan
Osakasayama Osaka, , Japan
Kawagoe Saitama, , Japan
Shimotsuke Tochigi, , Japan
Chuo-ku Tokyo, , Japan
Shinagawa-ku Tokyo, , Japan
Shinjuku-ku Tokyo, , Japan
Akita , , Japan
Aomori , , Japan
Kumamoto , , Japan
Kyoto , , Japan
Nagasaki , , Japan
Okayama , , Japan
Osaka , , Japan
Suwon-si Gyeonggi-do, 44338, Korea, Republic of
Busan , 60273, Korea, Republic of
Goyang , 602-7, Korea, Republic of
Jeollanam-do , 519-8, Korea, Republic of
Seoul , 110-7, Korea, Republic of
Seoul , 120-7, Korea, Republic of
Seoul , 13571, Korea, Republic of
Seoul , 13770, Korea, Republic of
Seoul , 138-7, Korea, Republic of
Seoul , 156-7, Korea, Republic of
Gdansk , 80-95, Poland
Opole , 45-37, Poland
Wroclaw , 50-36, Poland
Badalona , 08025, Spain
Barcelona , 08035, Spain
Barcelona , 08036, Spain
Barcelona , 08916, Spain
Girona , 17007, Spain
L'Hospitalet de Llobregat , 08907, Spain
Salamanca , 37007, Spain
Valencia , 46026, Spain
Kaohsiung , 112, Taiwan
Kaohsiung , 83301, Taiwan
Taichung City , 40705, Taiwan
Taichung , 404, Taiwan
Tainan , 704, Taiwan
Taipei , 10002, Taiwan
Taipei , 10449, Taiwan
Taipei , 112, Taiwan
Taipei , 114, Taiwan
Taoyuan , 33305, Taiwan
Ankara , 06100, Turkey
Ankara , 06500, Turkey
Bournemouth , BH7 7, United Kingdom
Harrow , HA1 3, United Kingdom
Manchester , M13 9, United Kingdom
Plymouth , PL6 8, United Kingdom
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