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

NCT ID: NCT00462761

Last Updated: 2020-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 76 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-01-31
• Study Completion Date: 2009-12-31

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.

Detailed Description

This is a multi-center clinical study conducted in the USA and two international sites. This open-label, dose escalation study was designed to characterize the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of orally administered AC220 as a single agent given daily for 14 days. Cohorts of 3 patients received AC220 until dose limiting toxicity was noted (DLT). At that point cohorts expanded to 6 patients until MTD was determined. Patients not experiencing DLT or significant disease progression at Day 15 may have continued receiving AC220 at the discretion of the Investigator and Sponsor. FLT3 positive and negative patients were allowed to participate.

Conditions

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

AC220

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

Group Type: EXPERIMENTAL

AC220

Intervention Type: 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.

Interventions

AC220

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.

Intervention Type: DRUG

Other Intervention Names

Quizartinib

Eligibility Criteria

Inclusion Criteria

1. Males and females age ≥ 18 years;

2. 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:

1. Refractory to at least 1 cycle of induction chemotherapy, or

2. Relapsed after at least 1 cycle of induction chemotherapy, or

3. Patient is not, according to the clinical judgment of the Principal Investigator, a candidate for induction chemotherapy due to age, comorbidity, or other factors;

3. 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;

4. Eastern Cooperative Oncology Group (ECOG) performance status of 0-3;

5. 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;

6. Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be less than Grade 2;

7. Serum creatinine ≤ 2.0 mg/dL;

8. Total serum bilirubin ≤ 1.5 × ULN unless considered due to Gilbert's syndrome or leukemic organ involvement;

9. Serum AST or ALT ≤ 3.0 × ULN unless considered due to leukemic organ involvement;

10. Females of childbearing potential must have a negative pregnancy test (urine β-hCG);

11. Females of childbearing potential and sexually mature males must agree to use a medically accepted method of contraception throughout the study;

12. Written informed consent must be provided.

Exclusion Criteria

1. Histologic diagnosis of acute promyelocytic leukemia;

2. Clinically active central nervous system leukemia;

3. 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);

4. Bone marrow transplant within 2 months prior to study;

5. Active, uncontrolled infection;

6. Major surgery within 4 weeks prior to study;

7. Radiation therapy within 4 weeks prior to, or concurrent with, study;

8. Human immunodeficiency virus positivity;

9. Active hepatitis B or C or other active liver disease;

10. Women who are pregnant, lactating, or unwilling to use contraception if of childbearing potential;

11. 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Daiichi Sankyo

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Director

Role: STUDY_DIRECTOR

Daiichi Sankyo

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Nebraska Medical Center

Omaha, Nebraska, United States

MD Anderson Cancer Center

Houston, Texas, United States

Chemotherapy and Immunotherapy Clinic

T'Bilisi, , Georgia

Hematology and Chemotherapy Clinic

T'bilisi, , Georgia

Countries

United States; Georgia

References

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.

Reference Type: DERIVED

PMID: 24002496 (View on PubMed)

Other Identifiers

CP0001

Identifier Type: -

Identifier Source: org_study_id