A Study of AC220 Given After Transplant in Subjects With Acute Myeloid Leukemia (AML)

A Phase 1 Study of AC220 (ASP2689) as Maintenance Therapy in Subjects With Acute Myeloid Leukemia Who Have Been Treated With an Allogeneic Hematopoietic Stem Cell Transplant

The purpose of this study is to define a safe dose of AC220 when given as maintenance therapy after treatment with an allogeneic stem cell transplant.

Study Overview

• Status: Completed
• Conditions: Leukemia, Myeloid, Acute
• Intervention / Treatment: Drug: AC220

Detailed Description

This is a two-part, sequential group dose escalation study.

In Part 1, subjects will be enrolled into successive cohorts to determine the maximum tolerated dose (MTD). Dose escalation decision will be made based on dose limiting toxicities (DLTs) that occur in subjects treated to date at a given dose level. In Part 2, a confirmation cohort will be opened to confirm the safety at the MTD.

Subjects who have had an allogeneic Hematopoietic Stem Cell Transplant (HSCT) will enter treatment with AC220 between 30 to 60 days after receiving allogeneic HSCT. AC220 will be administered every day, with 28 consecutive days defined as a treatment cycle. Subjects may receive up to 24 continuous treatment cycles. Subjects will have study visits each week for the first 2 cycles, and then on Day 1 of each cycle after that.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota
  • Texas
    • Houston, Texas, United States, 77030
      • M.D. Anderson Cancer Center
  • Washington
    • Seattle, Washington, United States, 98109
      • Seattle Cancer Care Alliance

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subject has a diagnosis of acute myeloid leukemia (AML) according to WHO classification (2008) and has received a high dose or a reduced intensity conditioning allogeneic Hematopoietic Stem Cell Transplant (HSCT) during first or second remission and within 30 to 60 days prior to first dose of AC220. Donors may be human leukocyte antigen (HLA)-matched for HLA-A, B, C, DRB1, and DQB1 by high resolution typing, related or unrelated (only a single allele disparity will be allowed for HLA-A, B, or C as defined by high resolution typing) Note: more than one HSCT is allowed
• Subject must be in morphologic remission (< 5% marrow blasts) and without active central nervous system (CNS) AML within 14 days prior to first dose of AC220
• Subject must have CD3 donor chimerism > 50 % at Screening
• Subject has a Karnofsky Performance Status (KPS) of ≥ 60
• Subject must have absolute neutrophil count (ANC) > 1000/mm3 and platelet count > 50,000/mm3 without platelet transfusion support within 2 weeks prior to first dose
• Subject must have adequate renal, hepatic, and coagulation parameters
• Female subjects must not be lactating and must not be breastfeeding at Screening or during the study period and for 28 days [or five half lives of the study drug whichever is longer] after final study drug administration.
• Subject is able to comply with study procedures and follow-up examinations

Exclusion Criteria:

• Subject received AC220 and relapsed during treatment with AC220
• Subject has active ≥ Grade 2 graft versus host disease (GVHD)
• Subject has received concurrent chemotherapy, immunotherapy, or radio-therapy within 21 days prior to the first dose of AC220, or any antineoplastic therapy that is considered to be investigational (i.e., used for non-approved indications(s) and in the context of a research investigation) within 30 days or 5 half-lives (whichever is longer) prior to the first dose of study drug
• Subject requires treatment with concomitant drugs that prolong QT/QTc interval or strong cytochrome P-3A4 (CYP3A4) inhibitors or inducers with the exception of immunosuppressants, antibiotics, antifungals, and antivirals that are used as standard of care post-transplant or to prevent or treat infections and other such drugs that are considered absolutely essential for the care of the subject
• Subject requires treatment with anticoagulant therapy
• Subject has a known positive test for human immunodeficiency virus, hepatitis C, or hepatitis B surface antigen
• Subject had major surgery within 4 weeks prior to first dose of AC220
• Subject has uncontrolled or significant cardiovascular disease
• Subject has an active acute fungal, bacterial, or other infection that is unresponsive to therapy
• Subject has participated in any interventional clinical study or has been treated with any investigational drugs within 30 days or 5 half lives whichever is longer, prior to the initiation of Screening.
• Subject has 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: AC220	Drug: AC220; Oral Liquid; Other Names: quizartinib; ASP2689

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of dose limiting toxicity (DLT)	From first dose through last dose of Cycle 2	up to Day 56
Safety assessed by recording adverse events, physical examinations, vital signs, electrocardiograms (ECGs) and laboratory assessments		30 days after last subject discontinues treatment (maximum of 24 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of confirmed complete remission (CR)	Time from first dose until date of relapse	24 months
Duration of overall complete remission	Complete remission (CR) + CR with incomplete platelet recovery (CRp) + CR with incomplete hematologic recovery (CRi) + complete molecular remission (CRm)	24 months
Disease-free survival	Time from first dose until date of relapse or death	30 days after last subject discontinues treatment (maximum of 24 months)
Overall survival	Time from first dose until date of death from any cause	30 days after last subject discontinues treatment (maximum of 24 months)
Percentage of transplant rejections	Through End of Treatment	30 days after last subject discontinues treatment (maximum of 24 months)
Percentage of Subjects with Graft-versus-Host Disease (GVHD)		Up through 24 months of treatment
Percentage of Donor Chimerism		Up through 24 months of treatment
Treatment-related mortality (TRM)	Death in CR (CR, CRm, CRp and CRi)	Up through 24 months of treatment
Composite of pharmacokinetics: AUC24 , Cmax, Ctrough and Tmax		Up through 24 months of treatment

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: Ambit Biosciences Corporation

Study record dates

Study Major Dates

• Study Start: April 1, 2012
• Primary Completion (Actual): March 1, 2015
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: November 7, 2011
• First Submitted That Met QC Criteria: November 7, 2011
• First Posted (Estimate): November 9, 2011

Study Record Updates

• Last Update Posted (Actual): February 12, 2019
• Last Update Submitted That Met QC Criteria: February 8, 2019
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Pharmacokinetics; Stem Cell Transplantation; Transplantation; Acute Myeloid Leukemia (AML); Allogeneic Transplantation; Kinase Inhibitor; Kinase; AC220; FMS-like tyrosine kinase (FLT3); FMS-like tyrosine kinase (FLT3) Inhibitor; ASP2689; quizartinib
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute
• Other Study ID Numbers: 2689-CL-0011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified individual participant data (IPD) and applicable supporting clinical trial documents may be available upon request at https://vivli.org/. In cases where clinical trial data and supporting documents are provided pursuant to our company policies and procedures, Daiichi Sankyo will continue to protect the privacy of our clinical trial participants. Details on data sharing criteria and the procedure for requesting access can be found at this web address: https://vivli.org/ourmember/daiichi-sankyo/
• IPD Sharing Time Frame: Studies for which the medicine and indication have received European Union (EU) and United States (US), and/or Japan (JP) marketing approval on or after 01 January 2014 or by the US or EU or JP Health Authorities when regulatory submissions in all regions are not planned and after the primary study results have been accepted for publication.
• IPD Sharing Access Criteria: Formal request from qualified scientific and medical researchers on IPD and clinical study documents from clinical trials supporting products submitted and licensed in the United States, the European Union and/or Japan from 01 January 2014 and beyond for the purpose of conducting legitimate research. This must be consistent with the principle of safeguarding study participants' privacy and consistent with provision of informed consent.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Clinical Study Report (CSR)