Ignite Creation Date:
2024-05-05 @ 11:39 AM
Last Modification Date:
2024-10-26 @ 9:11 AM
Study NCT ID:
NCT00101231
Status:
TERMINATED
Last Update Posted:
2013-06-04
First Post:
2005-01-07
Brief Title:
Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia
Sponsor:
National Cancer Institute NCI
Organization:
National Cancer Institute NCI
Study Overview
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
Status:
TERMINATED
Status Verified Date:
2013-06
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
This phase I trial is studying the side effects and best dose of flavopiridol in treating patients with relapsed or refractory acute myeloid leukemia acute lymphoblastic leukemia or chronic myelogenous leukemia Drugs used in chemotherapy such as flavopiridol work in different ways to stop the growth of cancer cells either by killing the cells or by stopping them from dividing
Detailed Description:
PRIMARY OBJECTIVES
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
SECONDARY OBJECTIVES
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
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
SECONDARY OBJECTIVES
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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| OSU 0479 | None | None | None |
| NCI-6947 | None | None | None |
| OSU-2004C0085 | None | None | None |
| OSU-0479 | None | None | None |
| CDR0000404374 | None | None | None |
| U01CA076576 | NIH | None | httpsreporternihgovquickSearchU01CA076576 |