Open Label Study to Evaluate Safety and Efficacy of 2 Doses of Quizartinib in Patients With Relapsed or Refractory Acute Myeloid Leukemia

NCT01565668 | Completed Phase 2 Results

• 2 other identifiers: 2689-CL-20042011-005408-13
• Study Type: interventional
• Target: 76
• Locations: 4 countries
• Sites: 24

Brief Summary

This study will evaluate two doses of Quizartinib in patients with relapsed or refractory acute myeloid leukemia who are also FMS-like tyrosine kinase - internal tandem duplication ( FLT3-ITD) positive. Patient will be randomly assigned in a 1:1 ratio to one of two treatment arms. Both treatment arms will receive Quizartinib but at different doses. The study treatment is taken orally in 28 day cycles until either disease progression occurs or an unacceptable toxicity occurs. In addition to the study assessments to evaluate the disease, blood will be drawn to measure drug levels and biomarkers. Patients will be followed for survival at three month intervals after the end of treatment.

Conditions

Leukemia, Myeloid, Acute

Keywords

FLT3-ITD positive Acute Myeloid Leukemia (AML); AC220; Relapse; Refractory

Outcome Measures

Primary Outcomes (1)

• Number of Participants Who Achieved Composite Complete Response (CRc) (Intent-to-Treat Population)

  CRc is defined as Complete remission (CR) + Complete remission with incomplete platelet recovery (CRp) + Complete remission with incomplete hematological recovery (CRi). * Participants with CR must have normal hematopoietic cells and achieved a morphologic leukemia-free state (\<5% bone marrow blasts in bone marrow, no blasts with Auer rods and no persistence of extramedullary disease) and must have had an absolute neutrophil count (ANC) ≥1 × 10\^9/L and platelet count ≥100 × 10\^9/L and were red blood cell (RBC) and platelet transfusion independent. Blasts in the peripheral blood was to be ≤1% (if blood sample was available). * Participants with CRp must have achieved CR except for incomplete platelet recovery (\< 100 ×10\^9/L). * Participants with CRi must have fulfilled all the criteria for CR except for incomplete hematological recovery with residual neutropenia \<1 × 10\^9/L with or without complete platelet recovery. RBC and platelet transfusion independence were not required.

  At end of Cycle 2 (after two complete 28-day cycles post treatment)

Secondary Outcomes (8)

• Number of Participants Who Achieved Complete Remission (CR) (Intent-to-Treat Population)

  At end of treatment visit (approximately 3 years post treatment)

• Overall Survival (OS) After Approximately 3 Years (Intent-to-Treat Population)

  Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

• Event Free Survival (EFS) After Approximately 3 Years (Intent-to-Treat Population)

  Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

• Leukemia Free Survival (LFS) After Approximately 3 Years (Intent-to-Treat Population)

  Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

• Duration of Remission After Approximately 3 Years (Intent-to-Treat Population)

  Evaluated at end of study, up to 6 months (approximately 3 years post treatment)

Study Arms (2)

AC220 Dose Level 1

EXPERIMENTAL

Drug: AC220

AC220 Dose Level 2

EXPERIMENTAL

Drug: AC220

Interventions

AC220 DRUG

oral

Also known as: Quizartinib, ASP2689

AC220 Dose Level 1; AC220 Dose Level 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has morphologically documented primary acute myeloid leukemia (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 hematopoietic stem cell transplantation (HSCT)
• Subject is positive for FLT3-ITD activating mutation in bone marrow or peripheral blood (\>10% allelic ratio)
• Eastern Cooperative Oncology Group performance status of 0 to 2
• 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 (14 days) for prior cytotoxic agents or at least 5 half-lives for prior noncytotoxic agents, including immunosuppressive therapy post HSCT
• Persistent chronic clinically significant nonhematological toxicities from prior treatment (including chemotherapy, kinase inhibitors, immunotherapy, experimental agents, radiation, HSCT, or surgery) must be Grade ≤ 1
• Patients - both males and females - with reproductive potential are eligible

You may not qualify if:

• Subject received previous treatment with AC220
• Subject has a diagnosis of acute promyelocytic leukemia
• Subject has a diagnosis of chronic myelogenous leukemia (CML) in blast crisis
• Subject has AML or antecedent MDS secondary to prior chemotherapy
• Subject has had HSCT and has either of the following:
• Donor lymphocyte infusion (DLI) is not permitted during the study or \< 30 days prior to study entry
• Subject has clinically active central nervous system (CNS) leukemia. A subject is considered eligible if CNS leukemia is controlled and subject is receiving intrathecal (IT) therapy at study entry. Subjects should continue to receive IT therapy (or cranial radiation) as clinically indicated
• Subject has received concurrent chemotherapy, immunotherapy, or radiotherapy within 14 days prior to the first dose of AC220, or any ancillary 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 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 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, including
• Subject has a pre-existing disorder predisposing the subject to a serious or life-threatening infection (e.g. cystic fibrosis, congenital or acquired immunodeficiency, bleeding disorder, or cytopenias not related to AML)
• Subject has an active uncontrolled acute or chronic systemic fungal, bacterial, viral, or other infection

Sponsors & Collaborators

• Daiichi Sankyo: lead
• Ambit Biosciences Corporation: collaborator

Study Sites (24)

UCLA School of Medicine

Los Angeles, California, 90095, United States

Location

Northwestern University

Chicago, Illinois, 60611, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

University of Maryland Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

John Hopkins University

Baltimore, Maryland, 21231, United States

Location

Tufts University School of Medicine-Tufts Medical Center

Boston, Massachusetts, 02111, United States

Location

University of Minnesota

Minneapolis, Minnesota, 55455, United States

Location

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10021, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

Penn State Milton S. Hershey Medical Center

Hershey, Pennsylvania, 17033, United States

Location

Hospital of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Medical University of South Carolina, Hollings Cancer Center

Charleston, South Carolina, 29403, United States

Location

Vanderbilt University, Vanderbilt Ingram Cancer Center

Nashville, Tennessee, 37232, United States

Location

UT Southwestern Medical Center, Simmons Cancer Center

Dallas, Texas, 75390, United States

Location

MD Anderson

Houston, Texas, 77030, United States

Location

Fred Hutchinson Cancer Research Center

Seattle, Washington, 98109, United States

Location

CHU d'Angers

Angers, 49033, France

Location

CHU de Grenoble

Grenoble, 38043, France

Location

Hôpital Saint Antoine

Paris, 75571, France

Location

Hôpital Haut Lévêque

Pessac, 33600, France

Location

Universitaria Policlinico S. Orsola Malpighi, Institute of Hemtology "L. & A. Seragnoli"

Bologna, 40138, Italy

Location

Nottingham University Hospitals

Nottingham, England, United Kingdom

Location

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Recurrence

Interventions

quizartinib

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Daiichi Sankyo
• Organization: Contact for Clinical Trial Information

CTRinfo@dsi.com

1-908-992-6400

Study Officials

• Global Clinical Leader

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 27, 2012
• First Posted: March 29, 2012
• Study Start: April 1, 2012
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: December 27, 2019
• Results First Posted: December 27, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• 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.
• 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.

Locations

US (18); IT (1); GB (1); FR (4)