Ignite Creation Date:
2024-05-05 @ 6:41 PM
Last Modification Date:
2024-10-26 @ 9:35 AM
Study NCT ID:
NCT00524667
Status:
TERMINATED
Last Update Posted:
2011-07-20
First Post:
2007-08-31
Brief Title:
HDAC Inhibitor Valproic Acid as an Effective Therapy for Chronic Lymphocytic Leukemia
Sponsor:
CancerCare Manitoba
Organization:
CancerCare Manitoba
Study Overview
Official Title:
HDAC Inhibitor Valproic Acid as an Effective Therapy for Chronic Lymphocytic Leukemia
Status:
TERMINATED
Status Verified Date:
2011-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Terminated due to poor accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
OBJECTIVES
To investigate
the mechanism of Valproic Acid VPA-induced apoptosis in B-CLL
the ability of VPA in combination with standard chemotherapy or new antitumor agents to induce a synergistic antitumor effect in chronic lymphocytic leukemia CLL cells
the clinical efficacy of VPA in previously treated CLL patients
This will be an example of a translational research study where the results of our laboratory studies will be applied to a clinical trial in the CLL clinic at CancerCare Manitoba
To investigate
the mechanism of Valproic Acid VPA-induced apoptosis in B-CLL
the ability of VPA in combination with standard chemotherapy or new antitumor agents to induce a synergistic antitumor effect in chronic lymphocytic leukemia CLL cells
the clinical efficacy of VPA in previously treated CLL patients
This will be an example of a translational research study where the results of our laboratory studies will be applied to a clinical trial in the CLL clinic at CancerCare Manitoba
Detailed Description:
All participants will be treated with valproic acid VPA at a starting dose of 15 mgkgday orally in divided doses This dose produces a VPA plasma level of 346-693 μM and is the recommended starting dose for patients with seizure disorder Each week a pre-dose serum VPA level will be determined by immunoassay and the daily dose increased by 5 mgkgd to ensure a predose level 1mM Once the target dose has been achieved serum VPA levels will be determined on a monthly basis to ensure a pre dose level 1mM
After completing 28 days of therapy participants will be examined and have lab work drawn CBC with differential electrolytes BUN creatinine total protein albumin calcium LDH total and direct bilirubin ALTAST and β2-microglobulin Females of child bearing age will undergo a pregnancy test prior to each 28 day cycle For participants identified as having stable or progressive disease National Cancer Institute Criteria Fludarabine Flu therapy will be added to VPA on a 28 day cycle Oral Flu will be administered at a dose of 40 mgm2day on days 1-3 of a 28 day cycle in addition to VPA as described above Dose adjustments for Flu will be based on creatinine clearance All participants receiving fludarabine will receive irradiated blood products and pneumocystis carnii prophylaxis
Treatment will be continued with VPA Flu to a maximum of six 28 day cycles Therapy will be discontinued prior to six 28 day cycles if a the participant requests discontinuation b if the participant is unable to comply with the protocol c the medical care team thinks a change of therapy would be in the best interest of the participant d there is evidence of progressive disease after two cycles of VPA Flu e if the participant experiences unacceptable toxicity attributable to the study drugs such as 3 non-hematological toxicity or prolonged grade 4 hematological toxicity NCI common toxicity criteria Table 5 of the protocol f if the ASTALT increase to 6x the upper limit of normal or g the participant becomes pregnant
After completing 28 days of therapy participants will be examined and have lab work drawn CBC with differential electrolytes BUN creatinine total protein albumin calcium LDH total and direct bilirubin ALTAST and β2-microglobulin Females of child bearing age will undergo a pregnancy test prior to each 28 day cycle For participants identified as having stable or progressive disease National Cancer Institute Criteria Fludarabine Flu therapy will be added to VPA on a 28 day cycle Oral Flu will be administered at a dose of 40 mgm2day on days 1-3 of a 28 day cycle in addition to VPA as described above Dose adjustments for Flu will be based on creatinine clearance All participants receiving fludarabine will receive irradiated blood products and pneumocystis carnii prophylaxis
Treatment will be continued with VPA Flu to a maximum of six 28 day cycles Therapy will be discontinued prior to six 28 day cycles if a the participant requests discontinuation b if the participant is unable to comply with the protocol c the medical care team thinks a change of therapy would be in the best interest of the participant d there is evidence of progressive disease after two cycles of VPA Flu e if the participant experiences unacceptable toxicity attributable to the study drugs such as 3 non-hematological toxicity or prolonged grade 4 hematological toxicity NCI common toxicity criteria Table 5 of the protocol f if the ASTALT increase to 6x the upper limit of normal or g the participant becomes pregnant
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