Ignite Creation Date:
2024-05-05 @ 11:17 PM
Last Modification Date:
2024-10-26 @ 10:31 AM
Study NCT ID:
NCT01295593
Status:
UNKNOWN
Last Update Posted:
2012-06-07
First Post:
2011-02-10
Brief Title:
Low Dose CdA Combined With Valproic Acid VPA in Previously Treated B-cell Chronic Lymphocytic LeukemiaB-CLL
Sponsor:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Organization:
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
Study Overview
Official Title:
Phase I-II Study of Low Dose CdA Combined With Valproic Acid VPA in Previously Treated B-cell Chronic Lymphocytic Leukemia CLL Patients
Status:
UNKNOWN
Status Verified Date:
2012-06
Last Known Status:
RECRUITING
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:
Rationale New chemotherapeutic agents are needed in relapsing B-Cell Chronic Lymphocytic Leukemia B-CLL to overcome resistance of CLL cells Valproic acid VPA is an inhibitor of histone deacetylase HDAC used as an anticonvulsant and mood-stabilizing drug for decades VPA mediates apoptosis in CLL cells through caspase activation VPA shows toxicity toward CLL cells displaying alterations in the p53 pathway The combination of VPA with fludarabine or 2-Chlorodeoxyadenosine CdA Cladribine results in synergistic loss of B-CLL cell viability and significant increase in apoptosis The highest index of synergism is observed between VPA and CdA a purine nucleoside analog active in B-CLL
Study design Overall the study will be proposed to previously treated patients with advanced B-CLL who are not eligible for aggressive approaches and who exhibit progressive disease A total of 33 patients will be included Estimated enrolment time is 2 years
First part It is planned to start therapy with single VPA during 2 months targeting plasma levels that have been reported to be active in vitro toward CLL cells but that do not exceed therapeutic levels in seizure prevention and in parallel to verify whether cellular targets of VPA have been actually inhibited in leukemic B-lymphocytes
Second part After the VPA preloading period 2 months patients will be evaluated to receive CdA CdA will be given at 56 mgm²day intravenously during 3 days a reduced-dose schedule which is less toxic - at no obvious cost of loss of efficacy - as compared to the standard dosage of 5 days CdA was chosen because it displays the highest level of in vitro synergism with VPA Four monthly courses of CdA will be given Patients will then be evaluated VPA will be stopped at the time of response evaluation scheduled 28 days after the last course of CdA
Study design Overall the study will be proposed to previously treated patients with advanced B-CLL who are not eligible for aggressive approaches and who exhibit progressive disease A total of 33 patients will be included Estimated enrolment time is 2 years
First part It is planned to start therapy with single VPA during 2 months targeting plasma levels that have been reported to be active in vitro toward CLL cells but that do not exceed therapeutic levels in seizure prevention and in parallel to verify whether cellular targets of VPA have been actually inhibited in leukemic B-lymphocytes
Second part After the VPA preloading period 2 months patients will be evaluated to receive CdA CdA will be given at 56 mgm²day intravenously during 3 days a reduced-dose schedule which is less toxic - at no obvious cost of loss of efficacy - as compared to the standard dosage of 5 days CdA was chosen because it displays the highest level of in vitro synergism with VPA Four monthly courses of CdA will be given Patients will then be evaluated VPA will be stopped at the time of response evaluation scheduled 28 days after the last course of CdA
Detailed Description:
None
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