An Ascending Dose Study of KW-2449 in Acute Leukemias, Myelodysplastic Syndromes, and Chronic Myelogenous Leukemia
Non-randomized, open, dose ranging and dose scheduling study of ascending doses of KW-2449 in subjects with AML, ALL, MDS and CML.
Acute Myelogenous Leukemia
Acute Lymphoblastic Leukemia
Chronic Myelogenous Leukemia
|Study Design:||Allocation: Non-Randomized
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)|
- To determine maximum tolerated dose of KW-2449 using prespecified dose limiting toxicity definitions based on CTCAE, version 3.0 and to assess tolerability based on adverse events [ Time Frame: For duration of dosing ] [ Designated as safety issue: Yes ]
- Pharmacokinetics [ Time Frame: For duration of dosing ] [ Designated as safety issue: No ]
- Pharmacodynamics [ Time Frame: For duration of dosing ] [ Designated as safety issue: No ]
- Clinical Response [ Time Frame: For duration of dosing ] [ Designated as safety issue: No ]
|Study Start Date:||June 2006|
|Estimated Study Completion Date:||April 2008|
|Estimated 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.
|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 Hakko Kirin Pharma, Inc.|