An Ascending Dose Study of KW-2449 in Acute Leukemias, Myelodysplastic Syndromes, and Chronic Myelogenous Leukemia

NCT00346632 | Terminated Phase 1 Results DMC

• 1 other identifier: 2449-US-001
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 4

Brief Summary

Non-randomized, open, dose ranging and dose scheduling study of ascending doses of KW-2449 in subjects with AML, ALL, MDS and CML.

Conditions

Acute Myelogenous Leukemia; Acute Lymphoblastic Leukemia; Myelodysplastic Syndromes; Chronic Myelogenous Leukemia

Keywords

AML; ALL; MDS; CML; Kinase Inhibitor

Outcome Measures

Primary Outcomes (1)

• Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0

  In addition to the number of TEAEs, the number of serious TEAEs, the number of related TEAEs, the number of Grade 3-4 TEAEs, and the number of subjects who died or discontinued due to TEAEs were also assessed. The maximally tolerated dose (MTD) was also to be determined, but it was not actually reached in either arm.

  Baseline up to Cycle 2, Day 1

Secondary Outcomes (6)

• Observed Peak Plasma Concentration (Cmax)

  Days 1 and 14 (and Day 28 for Arm B) of Cycle 1

• Time to Peak Plasma Concentration (Tmax)

  Days 1 and 14 (and Day 28 for Arm B) of Cycle 1

• Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval))

  Days 1 and 14 (and Day 28 for Arm B) of Cycle 1

• Terminal Half Life (t 1/2)

  Days 1 and 14 (and Day 28 for Arm B) of Cycle 1

• Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1)

  Day 1 and either Day 14 or Day 28 of Cycle 1

Study Arms (1)

KW-2449

EXPERIMENTAL

Treatment with ascending doses of KW-2449

Drug: KW-2449

Interventions

KW-2449 DRUG

Sequential ascending oral doses of KW-2449 given for 14 or 28 days (modified by protocol amendment to only 14 days dosing).

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 (including APL refractory to all-trans retinoic acid and arsenic) that has relapsed or was not responsive to prior chemotherapy;
• Relapsed/refractory ALL;
• CML that has failed to respond or has lost a response to imatinib; and
• Advanced MDS (INT-2 and High risk by IPSS) with failure or intolerance to approved therapy.
• ECOG Performance Status score of 0, 1, or 2;
• 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 ULN; serum bilirubin ≤ 2 mg/dL (serum bilirubin may be ≤ 3.0 mg/dL in any subject with Gilbert's Syndrome); and
• For females of childbearing potential, a negative serum pregnancy test. Subjects, of childbearing potential, must use an Investigator-approved method of birth control.

You may not qualify if:

• Candidates for approved therapies;
• Concomitant treatment with any investigational agent, chemotherapy, radiotherapy, or immunotherapy;
• Active 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);
• Uncontrollable disseminated intravascular coagulation;
• Major surgery within the 28 days preceding the first dose KW-2449;
• Radiotherapy, or lack of recovery of any radiotherapy-related acute toxicity, within the 28 days preceding the first dose KW-2449;
• Treatment with systemic therapy for the underlying hematologic condition, or lack of recovery of toxicity from such treatment, within 28 days of the first dose of KW-2449, with the following exceptions: hydroxyurea for treatment of hyperleukocytosis (discontinued for at least 48 hours prior to the first dose of KW-2449); imatinib (discontinued for at least 48 hours prior to the first dose of KW-2449); and interferon (discontinued for at least 7 days prior to the first dose of KW-2449);
• Treatment with any other investigational agent, or lack of recovery of toxicity from such treatment, within the 28 days preceding the first dose of KW-2449;
• Positive serology for HIV;
• 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;
• Any evidence of chronic Graft versus Host Disease;
• Active autoimmune disease requiring immunosuppressive therapy;
• Female subjects who are pregnant or breast feeding;

Sponsors & Collaborators

• Kyowa Kirin, Inc.: lead

Study Sites (4)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Contact Kyowa

Princeton, New Jersey, 08540, United States

Location

Weill Cornell/New York Presbyterian Hospital

New York, New York, 10021, United States

Location

M.D. Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• 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 DERIVED

MeSH Terms

Conditions

Leukemia, Myeloid, Acute; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Myelodysplastic Syndromes; Leukemia, Myelogenous, Chronic, BCR-ABL Positive

Interventions

KW 2449

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Project Leader
• Organization: Kyowa Kirin Pharmaceutical Development, Inc.

clinical.info@kyowakirin.com

6099191100

Study Officials

• Matt Fujimori, MD

  Kyowa Kirin, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

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: June 28, 2006
• First Posted: June 30, 2006
• Study Start: June 1, 2006
• Primary Completion: April 1, 2008
• Study Completion: April 1, 2008
• Last Updated: May 17, 2024
• Results First Posted: August 12, 2016

Record last verified: 2024-04

Locations

US (4)