Ignite Creation Date:
2025-12-25 @ 12:43 AM
Ignite Modification Date:
2025-12-25 @ 10:55 PM
Study NCT ID:
NCT00524667
Status:
TERMINATED
Last Update Posted:
2011-07-20
First Post:
2007-08-31
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
HDAC Inhibitor Valproic Acid as an Effective Therapy for Chronic Lymphocytic Leukemia
Sponsor:
CancerCare Manitoba
Organization:
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 mg/kg/day 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 mg/kg/d 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, ALT/AST, 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 mg/m2/day 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 AST/ALT 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, ALT/AST, 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 mg/m2/day 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 AST/ALT increase to \> 6x the upper limit of normal or g) the participant becomes pregnant.
Study Oversight
Has Oversight DMC:
False
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?: