An Ascending Dose Study of KW-2449 in Acute Leukemias, Myelodysplastic Syndromes, and Chronic Myelogenous Leukemia
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Safety, Pharmacokinetic, and Pharmacodynamic Study of KW-2449 in Acute Leukemias (AML), Myelodysplastic Syndromes (MDS), and Chronic Myelogenous Leukemia (CML)|
- Safety of KW-2449 - Number of Participants With Treatment-related Adverse Events (TEAEs) as Assessed by NCI-CTCAE v3.0 [ Time Frame: Baseline up to Cycle 2, Day 1 ] [ Designated as safety issue: Yes ]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.
- Observed Peak Plasma Concentration (Cmax) [ Time Frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 ] [ Designated as safety issue: No ]
- Time to Peak Plasma Concentration (Tmax) [ Time Frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 ] [ Designated as safety issue: No ]
- Area Under the Plasma Concentration-time Curve From 0 to Tau (AUC (0-tau, Tau is the Dosing Interval)) [ Time Frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 ] [ Designated as safety issue: No ]
- Terminal Half Life (t 1/2) [ Time Frame: Days 1 and 14 (and Day 28 for Arm B) of Cycle 1 ] [ Designated as safety issue: No ]
- Accumulation Ratio (AUC 0-tau Day 14 or 28 / AUC 0-tau Day 1) [ Time Frame: Day 1 and either Day 14 or Day 28 of Cycle 1 ] [ Designated as safety issue: No ]
- Disease Response [ Time Frame: Day 14 (Arm A) or Day 28 (Arm B) for all cycles ] [ Designated as safety issue: No ]
Disease response (i.e., complete or partial remission) based on standard criteria:
Cheson BD, Bennett JM, Kopecky KJ, Buchner T, Willman CL, Estey EH, et al. Revised recommendations of the International Working Group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003 Dec 15;21(24):4642-4649.
Cheson BD, Bennett JM, Kantarjian H, Pinto A, Schiffer CA, Nimer SD, et al. Report of an international working group to standardize response criteria for myelodysplastic syndromes. Blood. 2000 Dec 1;96(12):3671-3674.
VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel. Criteria for use of Imatinib Mesylate (Gleevec®) [updated March 2002; cited 2005 Nov 16]. Available from: http://www.pbm.va.gov/archive/imatinibcriteria.pdf
|Study Start Date:||June 2006|
|Study Completion Date:||April 2008|
|Primary Completion Date:||April 2008 (Final data collection date for primary outcome measure)|
Treatment with ascending doses of KW-2449
Sequential ascending oral doses of KW-2449 given for 14 or 28 days (modified by protocol amendment to only 14 days dosing).
This is a Phase I open-label dose escalation study of KW-2449 in subjects with acute leukemias, high risk MDS, and CML who are not candidates for approved therapy. Over an 18-month period, the investigative sites collectively will enroll up to a total of 96 subjects. Subjects will be enrolled sequentially into 1 of 7 dose groups to evaluate 2 dosing schedules (Arm A = 14 consecutive days of dosing followed by a 7-28 day rest period as determined by recovery from any acute hematologic and non-hematologic toxicities, or Arm B = 28 consecutive days of dosing followed by a 7-28 day rest period, as determined by recovery from any acute hematologic and non-hematologic toxicities). The safety of a dose level in Arm A (14-day dosing regimen) will be established prior to enrollment of subjects in the same dose level in Arm B (28-day dosing regimen).
In April 2007 the protocol was amended to discontinue Arm B (28 consecutive days of dosing). The protocol will continue as planned for Arm A (14 days of consecutive dosing).
Enrollment will proceed until a maximum tolerated dose (MTD) has been established for each study Arm. Once the MTD has been reached, 12 additional subjects, with 1 or more of the hematologic conditions included in this study, may be enrolled at the MTD as an expanded safety cohort.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00346632
|United States, Maryland|
|Johns Hopkins Hospital|
|Baltimore, Maryland, United States, 21287|
|United States, New Jersey|
|Princeton, New Jersey, United States, 08540|
|United States, New York|
|Weill Cornell/New York Presbyterian Hospital|
|New York, New York, United States, 10021|
|United States, Texas|
|M.D. Anderson Cancer Center|
|Houston, Texas, United States, 77030|
|Study Director:||Matt Fujimori, MD||Kyowa Kirin Pharmaceutical Development, Inc.|