A Phase 2, Randomized, Open-Label Study of the Safety and Efficacy of Two Doses of Quizartinib (AC220; ASP2689) in Subjects with FLT3-ITD Positive Relapsed or Refractory Acute Myeloid Leukemia (AML)

Phase 1

Active, not recruiting

• Conditions: Acute Myeloid Leukemia (AML); MedDRA version: 14.1Level: HLGTClassification code 10024324Term: LeukaemiasSystem Organ Class: 10005329 - Blood and lymphatic system disorders; MedDRA version: 14.1Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: SOCClassification code 10029104Term: Neoplasms benign, malignant and unspecified (incl cysts and polyps)System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 14.1Level: HLTClassification code 10024291Term: Leukaemias acute myeloidSystem Organ Class: 10005329 - Blood and lymphatic system disorders; Therapeutic area: Diseases [C] - Blood and lymphatic diseases [C15]

• Registration Number: EUCTR2011-005408-13-IT
• Lead Sponsor: ASTELLAS PHARMA GLOBAL DEVELOPMENT, INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2012-06-15
• Study Completion: 2015-03-09
• Last Update Posted: 2021-12-21

Recruitment & Eligibility

• Status: Not Recruiting
• Sex: All
• Target Recruitment: 76

Inclusion Criteria

1. Subject has provided an Institutional Review Board (IRB)/Independent Ethics Committee (IEC)-approved signed Informed Consent and privacy disclosure as per national regulations (e.g., HIPAA Authorization for U.S. sites) prior to any studyrelated procedures (including withdrawal of prohibited medication, if applicable). 2. Subject is male or female =18 years of age. 3. Subject has morphologically documented primary AML or AML secondary to myelodysplastic syndrome (MDS) as defined by the World Health Organization (WHO) criteria, as determined by pathology review at the treating institution and has relapsed or is refractory after 1 second line (salvage) regimen or after HSCT (Appendix 8). 4. Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (>10% allelic ratio as determined by central lab). 5. ECOG performance status of 0 to 2 (Table 4). 6. In the absence of rapidly progressing disease clearly documented by the investigator, the interval from prior treatment to time of AC220 administration will be at least 2 weeks for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT. 7. Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade =1. 8. Subject must have adequate renal, hepatic, and coagulation parameters as indicated by the following laboratory values: ? Alkaline phosphatase(ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) =2.5 x institutional upper limit of normal (ULN) ? Total bilirubin =1.5 x institutional ULN ? Serum creatinine =1.5x institutional ULN and glomerular filtration rate (GFR)>30 mL/min (calculated by Cockcroft and Gault formula, Appendix 9). 9. Subject is able to comply with study procedures and follow-up examinations.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 35
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1.Previous treatment with AC220. 2.diagnosis of acute promyelocytic leukemia. 3.diagnosis of chronic myelogenous leukemia (CML) in blast crisis. 4.AML or antecedent MDS secondary to prior chemotherapy. 5.HSCT and either of the following: ? Is within 100 days of transplant ? Is still taking immunosuppressive drugs ? Has clinically significant graft-versus-host disease requiring treatment ? Has G>1 persistent nonhematological toxicity related to the transplant. 6.clinically active CNS leukemia. 7. concurrent chemotherapy, immunotherapy, or radiotherapy within 21 days prior to the first dose of AC220, or any ancillary therapy that is considered to be investigational within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug. 8.treatment with concomitant drugs that prolong QT/QTc interval or with strong inhibitors or inducers of cytochrome P450-isozyme3A4 (CYP3A4) with the exception of antibiotics, antifungals, and antivirals that are used as standard of care (See Appendix 1) 9.treatment with anticoagulant therapy. 10.known positive test for HIV, HCV, or HBV surface antigen. 11.major surgery within 4 weeks prior to first dose of AC220. 12.uncontrolled or significant cardiovascular disease (See Protocol) 13.Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection. 14. active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection. 15.any of the following laboratory values: ? Serum potassium <4.0 mmol/L despite supplementation, or >5.5 mmol/L. ? Serum magnesium 3 mg/dL (1.23 mmol/L). ? Serum calcium >11.5 mg/dL (2.9 mmol/L) or ionized calcium >1.5 mmol/L. 16.woman of childbearing potential or a male subject with female partner of childbearing potential who is unwilling or unable to use an acceptable contraceptive method to avoid pregnancy for the entire study period and for at least 3 months after the last dose of study drug. 17.female with a positive pregnancy test, pregnant, or breastfeeding. 18.any medical, psychiatric, addictive or other kind of disorder which compromises the ability of the subject to give written informed consent and/or to comply with procedures.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified