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

Leukemia, Myeloid, Acute Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01468467
• Other study ID #: 2689-CL-0011
• Status: Completed
• Phase: Phase 1
• Start date: April 2012
• Est. completion date: March 2015

Study information

• Verified date: November 2016
• Source: Daiichi Sankyo, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute

Intervention

Drug:
• AC220
Oral Liquid

Locations

Country	Name	City	State
United States	Northwestern University	Chicago	Illinois
United States	City of Hope	Duarte	California
United States	M.D. Anderson Cancer Center	Houston	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Seattle Cancer Care Alliance	Seattle	Washington

Sponsors (2)

Lead Sponsor	Collaborator
Daiichi Sankyo, Inc.	Ambit Biosciences Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of dose limiting toxicity (DLT)	From first dose through last dose of Cycle 2	up to Day 56
Primary	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	Duration of confirmed complete remission (CR)	Time from first dose until date of relapse	24 months
Secondary	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
Secondary	Disease-free survival	Time from first dose until date of relapse or death	30 days after last subject discontinues treatment (maximum of 24 months)
Secondary	Overall survival	Time from first dose until date of death from any cause	30 days after last subject discontinues treatment (maximum of 24 months)
Secondary	Percentage of transplant rejections	Through End of Treatment	30 days after last subject discontinues treatment (maximum of 24 months)
Secondary	Percentage of Subjects with Graft-versus-Host Disease (GVHD)		Up through 24 months of treatment
Secondary	Percentage of Donor Chimerism		Up through 24 months of treatment
Secondary	Treatment-related mortality (TRM)	Death in CR (CR, CRm, CRp and CRi)	Up through 24 months of treatment
Secondary	Composite of pharmacokinetics: AUC24 , Cmax, Ctrough and Tmax		Up through 24 months of treatment