Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
Adult Acute Basophilic Leukemia
Adult Acute Eosinophilic Leukemia
Adult Acute Megakaryoblastic Leukemia (M7)
Adult Acute Minimally Differentiated Myeloid Leukemia (M0)
Adult Acute Monoblastic Leukemia (M5a)
Adult Acute Monocytic Leukemia (M5b)
Adult Acute Myeloblastic Leukemia With Maturation (M2)
Adult Acute Myeloblastic Leukemia Without Maturation (M1)
Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities
Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)
Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)
Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)
Adult Acute Myelomonocytic Leukemia (M4)
Adult Erythroleukemia (M6a)
Adult Pure Erythroid Leukemia (M6b)
Blastic Phase Chronic Myelogenous Leukemia
Recurrent Adult Acute Lymphoblastic Leukemia
Recurrent Adult Acute Myeloid Leukemia
Relapsing Chronic Myelogenous Leukemia
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose Escalation Study of Flavopiridol (NSC 649890) Administered as a 30 Minute Loading Dose Followed by a 4-Hour Infusion in Patients With Relapsed and Refractory Acute Leukemias|
- Maximal tolerable dose of flavopiridol [ Time Frame: Day 21 ] [ Designated as safety issue: Yes ]
|Study Start Date:||October 2004|
|Primary Completion Date:||November 2012 (Final data collection date for primary outcome measure)|
Experimental: Treatment (flavopiridol)
Patients receive flavopiridol IV over 30 minutes followed by a 4-hour infusion on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression.
I. To determine the maximal tolerable dose of flavopiridol in relapsed or refractory acute leukemia in adults (Stratum 1) and children (Stratum 2).
II. To define the qualitative and quantitative toxicities of flavopiridol in regard to organ specificity, time course, predictability, and reversibility.
III. To determine the preliminary clinical activity of flavopiridol in adults (Stratum 1) and children (Stratum 2) using this novel schedule in acute leukemia.
IV. To evaluate the plasma and cellular pharmacokinetics of flavopiridol in patients enrolled on this study.
I. To measure pharmacodynamic measurements including effects on cell cycle; down modulation of bcl-2, mcl-1, XIAP, bax, RNA polymerase II phosphorylation; and signaling via the VEGF (VEGF, VEGF-R1, VEGF-R2, HIF-1), NF-Kappa B pathway, and PI3kinase pathway; and correlate with Css and other pharmacokinetic features.
II. To assess drug induced apoptosis of acute leukemia cells in vitro and subsequent relationship to clinical response based upon Css of flavopiridol attained in vivo.
II. To determine if increase in inflammatory cytokines (TNF-alpha, gamma-IFN, IL-6 and IL-8) correlate with pharmacokinetics, pharmacodynamics, laboratory (decrease in serum albumin) and clinical (hypotension observed with the first administration of flavopiridol) parameters of treatment.
OUTLINE: This is a dose-escalation study. Patients are stratified according to age group (adult [≥ 18 years] vs pediatric [1-17 years]).
Patients receive flavopiridol intravenously (IV) over 30 minutes followed by a 4-hour infusion on days 1-3. Treatment repeats every 21 days for up to 6 courses in the absence of unacceptable toxicity or disease progression. Cohorts of 3-6 patients receive escalating doses of flavopiridol until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Patients are followed up every 2 months for 1 year and then every 6 months for 4 years.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00101231
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||William Blum||Ohio State University|