Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia
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|ClinicalTrials.gov Identifier: NCT00101231|
Recruitment Status : Terminated
First Posted : January 10, 2005
Last Update Posted : June 4, 2013
|Condition or disease||Intervention/treatment||Phase|
|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||Drug: alvocidib||Phase 1|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||88 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||October 2004|
|Actual Primary Completion Date :||November 2012|
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.
- Maximal tolerable dose of flavopiridol [ Time Frame: Day 21 ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00101231
|United States, Ohio|
|Ohio State University Medical Center|
|Columbus, Ohio, United States, 43210|
|Principal Investigator:||William Blum||Ohio State University|