Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Study of KW-2449 in Acute Myelogenous Leukemia (AML) (Protocol Number: 2449-US-002)

NCT00779480 | Terminated Phase 1 DMC

• 1 other identifier: 2449-US-002
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 4

Brief Summary

To determine the maximum tolerated dose of KW-2449 in people with acute myelogenous leukemia who are not candidates for approved therapy. As well, the study will determine the response rate to KW-2449.

Conditions

Acute Myelogenous Leukemia (AML)

Keywords

Acute Myelogenous Leukemia; Safety; Dose Tolerance; Pharmacokinetics/Pharmacodynamics; FLT-3

Outcome Measures

Primary Outcomes (1)

• Safety as determine by adverse event rate and dose limiting toxicity

  Approximately 6 months

Secondary Outcomes (1)

• Hematologic activity/improvement, Pharmacokinetics/Pharmacodynamics

  Approximately 6 months

Study Arms (1)

KW-2449

EXPERIMENTAL

Sequential dose escalation in separate cohorts of 3+3 design from 450 mg/day to 800 mg/day total daily dose.

Drug: KW-2449

Interventions

KW-2449 DRUG

KW-2449 50 mg capsules administered 3 or 4 times per day for 21-day cycles up to 6 cycles

KW-2449

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of AML (excluding acute promyelocytic leukemia) that has relapsed or was not responsive to prior chemotherapy.
• Phase 2: Only subjects with the FLT3/ITD mutation will be enrolled in Phase 2.
• Eastern Cooperative Oncology Group (ECOG) Scale score17 of 0, 1, or 2 (refer to Appendix 1);
• Male or female, at least 18 years of age;
• Signed written informed consent;
• Serum creatinine ≤ 2.0 mg/dL;
• Serum SGOT (AST) and SGPT (ALT) ≤ 5x the upper limits of normal (ULN); serum bilirubin ≤ 2 mg/dL (serum bilirubin must be ≤ 3.0 mg/dL in any subject with Gilbert's Syndrome); and
• For women of childbearing potential, a negative serum pregnancy test must be obtained prior to administration of KW-2449.

You may not qualify if:

• Subjects who are candidates for approved therapies for their underlying condition;
• Prior treatment with KW-2449;
• Concomitant treatment with chemotherapy (systemic or intrathecal), radiotherapy, immunotherapy, or any investigational agent;
• Evidence of active central nervous system (CNS) leukemia;
• Previous or concurrent malignancy except noninvasive non-melanomatous skin cancer, in situ carcinoma of the cervix, or other solid tumor treated curatively, and without evidence of recurrence for at least 2 years prior to study entry;
• Uncontrolled systemic infection (viral, bacterial, or fungal);
• Uncontrolled disseminated intravascular coagulopathy;
• Major surgery within the 28 days preceding the first dose KW-2449;
• Radiotherapy within the 28 days preceding the first dose KW-2449, or lack of recovery from any radiotherapy-related acute adverse event;
• Treatment with approved systemic therapy for the underlying hematologic condition within 14 days of the first dose of KW-2449 with the exception of hydroxyurea (Hydrea®) or leukapheresis for hyperleukocytosis and/or thrombocytosis (see Concomitant Medication and Treatment), or lack of recovery from any adverse event from prior systemic therapy.
• Treatment with another investigational agent within the 28 days preceding the first dose of KW-2449, or lack of recovery from any adverse event from such treatment;
• Known positive serology for human immunodeficiency virus (type 1 and/or 2);
• Clinically significant cardiac dysfunction (New York Heart Association Class 3 or 4) at the time of screening, or a history of myocardial infarction or heart failure within 3 months preceding the first dose of KW-2449;
• Chronic Graft versus Host Disease (GVHD) with the exception of mild (Grade 1) skin GVHD;
• Phase 1 only: ≥ Grade 2 nausea or vomiting within 7 days preceding the first dose KW 2449;

Sponsors & Collaborators

• Kyowa Kirin Co., Ltd.: lead

Study Sites (4)

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins University

Baltimore, Maryland, 21231, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

St. Francis Hospital

Greenville, South Carolina, 29601, United States

Location

Related Publications (2)

• Pratz KW, Cortes J, Roboz GJ, Rao N, Arowojolu O, Stine A, Shiotsu Y, Shudo A, Akinaga S, Small D, Karp JE, Levis M. A pharmacodynamic study of the FLT3 inhibitor KW-2449 yields insight into the basis for clinical response. Blood. 2009 Apr 23;113(17):3938-46. doi: 10.1182/blood-2008-09-177030. Epub 2008 Nov 24.

  PMID: 19029442 BACKGROUND

• Shiotsu Y, Kiyoi H, Ishikawa Y, Tanizaki R, Shimizu M, Umehara H, Ishii K, Mori Y, Ozeki K, Minami Y, Abe A, Maeda H, Akiyama T, Kanda Y, Sato Y, Akinaga S, Naoe T. KW-2449, a novel multikinase inhibitor, suppresses the growth of leukemia cells with FLT3 mutations or T315I-mutated BCR/ABL translocation. Blood. 2009 Aug 20;114(8):1607-17. doi: 10.1182/blood-2009-01-199307. Epub 2009 Jun 18.

  PMID: 19541823 BACKGROUND

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Interventions

KW 2449

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

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: October 22, 2008
• First Posted: October 24, 2008
• Study Start: January 1, 2009
• Primary Completion: April 1, 2010
• Study Completion: December 1, 2010
• Last Updated: April 25, 2024

Record last verified: 2024-04

Locations

US (4)