A Phase I Study of AC220 in Patients With Relapsed/Refractory Acute Myeloid Leukemia Regardless of FLT3 Status

NCT00462761 | Completed Phase 1 Results

• 1 other identifier: CP0001
• Study Type: interventional
• Target: 76
• Locations: 2 countries
• Sites: 5

Brief Summary

Patients received oral AC220 daily for 14 days to study the side effects, tolerability and best dose for treating relapsed or refractory acute myeloid leukemia, regardless of FLT3 status.

Conditions

Acute Myeloid Leukemia; Leukemia; Myelodysplastic Syndrome; AML; MDS

Keywords

RTK; kinase; inhibitor; tyrosine; acute; FLT3; AC220; pharmacokinetic; pharmacokinetics; PK; pharmacodynamic; pharmacodynamics; mutations; PD; receptor; class III; relapsed; refractory; t(8;21); q22;q22; AML1/ETO; t(16;16; p13;q22; CBFbeta/MYH11; inv(16); p13q22; 11q23; dysplasia; myeloid; myelomonocytic; monoblastic; monocytic; erythroid; erythroleukemia; megakaryoblastic; basophilic; panmyelosis; myelofibrosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Treatment-Emergent Treatment Related Adverse Events Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Baseline up to 30 days post last dose

• Number of Participants With Treatment-emergent Treatment-related Grade 3 or 4 Adverse Events By At Least 10% of All Participants By Dose Group Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Baseline up to 30 days post last dose

Secondary Outcomes (4)

• Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Progressive Disease Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Baseline up to 28 days after the last dose, up to approximately 3 years

• Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Baseline up to 28 days after the last dose, up to approximately 3 years

• Number of Participants Achieving a Best Disease Response by Dose Cohort in Terms of Best Overall Response Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Baseline up to 28 days after the last dose, up to approximately 3 years

• Number of Participants With Hematologic Improvement Following Oral Administration of Quizartinib in Participants With Relapsed or Refractory Acute Myeloid Leukemia

  Baseline up to 28 days after the last dose, up to approximately 3 years

Study Arms (1)

AC220

EXPERIMENTAL

Determine safety, tolerability and pharmacokinetic (PK) parameters of AC220

Drug: AC220

Interventions

AC220 DRUG

Powder in bottle formulation supplied as 50mg or 350 mg in glass, crimped serum vials. Requires reconstitution by a pharmacist, and must be stored securely and protected from light.

Also known as: Quizartinib

AC220

Eligibility Criteria

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

You may qualify if:

• Males and females age ≥ 18 years;
• Histopathologically documented primary or secondary AML, as defined by WHO criteria (Jaffe et al, 2001), confirmed by pathology review at treating institution, meeting at least one of the following:
• Refractory to at least 1 cycle of induction chemotherapy, or
• Relapsed after at least 1 cycle of induction chemotherapy, or
• Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;
• Patients for whom no standard therapies are anticipated to result in a durable remission, or who have failed potentially curative therapy, or who refuse standard therapy or patients for whom there is no known therapy of documented treatment benefit;
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;
• In the absence of rapidly progressing disease, the interval from prior treatment to time of AC220 administration should be at least 2 weeks for cytotoxic agents (other than hydroxyurea, per Section 8.8), or at least 5 half-lives for noncytotoxic agents;
• Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;
• Serum creatinine ≤ 2.0 mg/dL;
• Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;
• Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;
• Females of childbearing potential must have a negative pregnancy test (urine β-hCG);
• Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;
• Written informed consent must be provided.

You may not qualify if:

• Histologic diagnosis of acute promyelocytic leukemia;
• Clinically active central nervous system leukemia;
• Persistent clinically significant toxicity from prior chemotherapy that is Grade 2 or higher by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE v3);
• Bone marrow transplant within 2 months prior to study;
• Active, uncontrolled infection;
• Major surgery within 4 weeks prior to study;
• Radiation therapy within 4 weeks prior to, or concurrent with, study;
• Human immunodeficiency virus positivity;
• Active hepatitis B or C or other active liver disease;
• Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;
• Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the judgment of the Principal Investigator, could jeopardize patient safety or interfere with the objectives of the study.

Sponsors & Collaborators

• Daiichi Sankyo: lead

Study Sites (5)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Chemotherapy and Immunotherapy Clinic

Tbilisi, Georgia

Location

Hematology and Chemotherapy Clinic

Tbilisi, Georgia

Location

Related Publications (1)

• Cortes JE, Kantarjian H, Foran JM, Ghirdaladze D, Zodelava M, Borthakur G, Gammon G, Trone D, Armstrong RC, James J, Levis M. Phase I study of quizartinib administered daily to patients with relapsed or refractory acute myeloid leukemia irrespective of FMS-like tyrosine kinase 3-internal tandem duplication status. J Clin Oncol. 2013 Oct 10;31(29):3681-7. doi: 10.1200/JCO.2013.48.8783. Epub 2013 Sep 3.

  PMID: 24002496 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Leukemia; Myelodysplastic Syndromes; Recurrence; Aortic aneurysm, familial thoracic 4; Leukemia, Erythroblastic, Acute; Primary Myelofibrosis

Interventions

quizartinib

Condition Hierarchy (Ancestors)

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

Results Point of Contact

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

CTRinfo@dsi.com

908-992-6400

Study Officials

• Clinical Director

  Daiichi Sankyo

  STUDY DIRECTOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 17, 2007
• First Posted: April 19, 2007
• Study Start: January 1, 2007
• Primary Completion: March 1, 2009
• Study Completion: December 1, 2009
• Last Updated: May 11, 2020
• Results First Posted: April 24, 2020

Record last verified: 2020-04

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

GE (2); US (3)