Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia
Acute Myeloid Leukemia (AML)
Acute Lymphocytic Leukemia (ALL)
Adult T Cell Leukemia (ATL)
Chronic Myeloid Leukemia (CML-BP)
Chronic Lymphocytic Leukemia (CLL)
Myelodysplastic Syndrome (MDS)
Chronic Myelomonocytic Leukemia (CMML)
Drug: Terameprocol (EM-1421)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase 1 Study of Terameprocol (EM-1421) a Survivin and Cyclin-Dependent Kinase-1 (Cdc2) Inhibitor, in Patients With Leukemia|
- Safety, maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia [ Time Frame: Adverse events and toxicity will be assessed prior to each cycle of treatment and at times when clinically indicated. ] [ Designated as safety issue: Yes ]
- Pharmacokinetics (PK) of Terameprocol (EM-1421) given as intravenous infusion three times a week in patients with leukemia [ Time Frame: Pharmacokinetics samples will be collected only on the first cycle of treatment with study drug from immediately prior to first study drug infusion to the end of day 12 of infusion. ] [ Designated as safety issue: No ]
- To access anti-tumor activity [ Time Frame: Pharmacodynamic (molecular markers) samples will be collected immediately prior to, day 5 pre-dose and post-dose day 12 of each cycle of study drug administration, at remission and at relapse/or end of study (whichever occurs first). ] [ Designated as safety issue: No ]
|Study Start Date:||August 2007|
|Study Completion Date:||June 2009|
|Primary Completion Date:||March 2009 (Final data collection date for primary outcome measure)|
Experimental: Terameprocol (EM-1421)
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off).
Drug: Terameprocol (EM-1421)
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off.
The dose of Terameprocol (EM-1421) will be escalated in successive cohorts of 3 patients. Patients will be entered sequentially on each dose level. If none of the first 3 patients at a dose level experience first cycle drug related dose-limiting toxicity (DLT), new patients may be entered at the next higher dose level. If 1 of 3 patients experience first cycle DLT, up to 3 more patients are started at that same dose level. If 2 or more experience first cycle DLT, no further patients are started at that dose. The MTD is the highest dose level in which <2 patients of 6 develop a first cycle DLT. New dose levels may begin accrual only if all patients at the current dose level have been observed for a minimum of 3 weeks after the last infusion of Terameprocol (EM-1421). The recommended phase 2 dose (RP2D) will be the MTD unless significant clinical activity is seen below the MTD.
During the observation period of 3 weeks, additional accrual to a previously assessed lower dose level, with no documented DLTs, will be allowed with sponsor approval.
Patients will be treated three times a week, with at least one day in between infusions, for two weeks followed by one week of rest. The dose for new cohorts will be escalated from 1000, to 1500 and 2200 mg or de-escalated to 500 mg if 1000 mg exceeds the MTD. The principal investigator will consult with the sponsor to determine the appropriate dose level for a new patient. At the MTD, up to 10 additional patients may be accrued in that dose cohort to further define the toxicities and response of the agent. If the initial dose level exceeds the MTD, a fallback dose level of 500 mg will be implemented.
Patients are allowed to be treated with subsequent cycles of Terameprocol (EM-1421) until disease progression or until severe toxicities occur and side effects do not outweigh the benefit of study drug administration in the assessment of the treating physician.
Intrapatient dose escalation Intrapatient dose escalation by one dose level may be permitted, but only if at least 3 patients in the next higher dose level have been treated and have been followed for 21 days without experiencing DLT. Decisions for intrapatient dose escalation will be made jointly by the Study Sponsor, treating physician and Principal Investigator.
Terameprocol (EM-1421) as a single agent given intravenously over 6 hours three times a week for two weeks followed by one week rest (two weeks on, one week off)in the following dose cohorts starting with 1000 mg dose cohort.
Dose Level -1: 500 mg
Dose Level 1: 1000 mg
Dose Level 2: 1500 mg
Dose Level 3: 2200 mg
Please refer to this study by its ClinicalTrials.gov identifier: NCT00664677
|United States, North Carolina|
|UNC, Lineberger Comprehensive Cancer Center|
|Chapel Hill, North Carolina, United States, 27599|
|Study Director:||Neil Frazer, MB, ChB||Erimos Pharmaceutical|