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

Sponsor

Daiichi Sankyo, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01468467

Collaborator

Ambit Biosciences Corporation (Industry)

Enrollment

Locations

Arm

Duration (Months)

2.6

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Leukemia, Myeloid, Acute	Drug: AC220	Phase 1

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 Design

Study Type:

Interventional

Actual Enrollment :

13 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2012

Actual Primary Completion Date :

Mar 1, 2015

Actual Study Completion Date :

Mar 1, 2015

Arms and Interventions

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

Arm

Intervention/Treatment

Experimental: AC220

Drug: AC220

Oral Liquid

Other Names:

quizartinib

ASP2689

Outcome Measures

Primary Outcome Measures

Incidence of dose limiting toxicity (DLT) [up to Day 56]
From first dose through last dose of Cycle 2
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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Northwestern University	Chicago	Illinois	United States	60611
3	University of Minnesota	Minneapolis	Minnesota	United States	55455
4	M.D. Anderson Cancer Center	Houston	Texas	United States	77030
5	Seattle Cancer Care Alliance	Seattle	Washington	United States	98109