Clinical Trial Results:
Phase I-II study of low dose CdA combined with valproic acid (VPA) in previously treated B-cell chronic lymphocytic leukemia (CLL) patients.
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Summary
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EudraCT number |
2010-019983-35 |
Trial protocol |
BE |
Global end of trial date |
18 Sep 2013
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Results information
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Results version number |
v1(current) |
This version publication date |
17 Mar 2021
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First version publication date |
17 Mar 2021
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
VPA-CdA
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT01295593 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Cliniques universitaires Saint-Luc- Université Catholique de Louvain
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Sponsor organisation address |
Avenue Hippocrate 10, Brussels, Belgium, 1200
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Public contact |
Eric Van Den Neste, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, 0032 27641875, eric.vandenneste@uclouvain.be
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Scientific contact |
Eric Van Den Neste, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, 0032 27641875, eric.vandenneste@uclouvain.be
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
18 Sep 2013
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
18 Sep 2013
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine the tolerability of VPA in combination with low dose CdA in patients with advanced B-CLL
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Protection of trial subjects |
This study will be conducted according to the principles of the “Helsinki Declaration”, of the, International Conference on Harmonization (ICH)’s Good Clinical Practice Guidelines, national law and reglementation pertaining to clinical studies.
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Background therapy |
VPA : daily, oral, starting dose 10mg/kg/day total dose, taken in 2 separate administrations of around 5 mg/kg/day each, for a maximum of 6 months. CdA : 5.6 mg/m²/day IV during 3 days, every 28 days, for a maximum of 4 cycles. | ||
Evidence for comparator |
Not applicable | ||
Actual start date of recruitment |
24 Nov 2010
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Belgium: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
3
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From 65 to 84 years |
7
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85 years and over |
0
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Recruitment
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Recruitment details |
A total of 11 patients were included between March 2011 and August 2013 in several centers in Brussels. In Luxembourg, no patient was included. The eleventh patient was included on August 23, 2013, only this patient was not included in the analyzes. Ten patients can be analyzed after a median follow-up of 10.6 months. | ||||||
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Pre-assignment
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Screening details |
All patients had given written informed consent prior to any study-specific examination or procedure. Patients were evaluated within 28 days of the first administration of the study treatment. However, hematology and blood chemistry tests (including creatinine clearance) have been carried out within 7 days of the first day of treatment. | ||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||
Allocation method |
Not applicable
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Blinding used |
Not blinded | ||||||
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Arms
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Arm title
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Valproic acid and 2-chlorodeoxyadenosine | ||||||
Arm description |
VPA : daily, oral, starting dose 10mg/kg/day total dose, taken in 2 separate administrations of around 5 mg/kg/day each, for a maximum of 6 months. CdA : 5.6 mg/m²/day IV during 3 days, every 28 days, for a maximum of 4 cycles. | ||||||
Arm type |
Experimental | ||||||
Investigational medicinal product name |
Valproic acid
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Investigational medicinal product code |
VPA
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Other name |
Depakine
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Pharmaceutical forms |
Cachet
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Routes of administration |
Oral use
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Dosage and administration details |
VPA / 5/mg /kg twice a day, per os
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Investigational medicinal product name |
2-chlorodeoxyadenosine
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Investigational medicinal product code |
CdA
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Other name |
Cladribine
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Pharmaceutical forms |
Injection
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Routes of administration |
Intravenous use
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Dosage and administration details |
CdA / 5,6 mg/m²/day during 3 days, every 28 days, IV, for 4 cycles
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
Patients receiving VPA / 5/mg /kg twice a day, per os and CdA / 5,6 mg/m²/day during 3 days, every 28 days, IV, for 4 cycles | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Valproic acid and 2-chlorodeoxyadenosine
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Reporting group description |
VPA : daily, oral, starting dose 10mg/kg/day total dose, taken in 2 separate administrations of around 5 mg/kg/day each, for a maximum of 6 months. CdA : 5.6 mg/m²/day IV during 3 days, every 28 days, for a maximum of 4 cycles. | ||
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End point title |
To determine the tolerability of VPA in combination with low dose CdA in patients with advanced B- Chronic Lymphocytic Leukemia [1] | ||||||||
End point description |
The primary endpoint was defined as the rate of patients developing toxicities during combination
therapy with valproic acid and low dose CdA2-chlorodeoxyadenosine.
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End point type |
Primary
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End point timeframe |
After 7 months of treatment
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: The primary endpoint for sample size estimation has been defined as the rate of patients developing toxicities under the combined treatment. A two-stages Simon design was used. In the first step, 10 patients needed to be included. If strictly less than 6 patients are free of toxicity, the trial would be stopped prematurely. Otherwise, the study would go on until 33 patients will have been treated by the combination. |
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| No statistical analyses for this end point | |||||||||
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End point title |
Progression free survival | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
PFS was the time interval between the date of inclusion and the date of progressive disease or death
from any cause.
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| No statistical analyses for this end point | |||||||||
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End point title |
overall survival (OS) | ||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
OS was defined as the time interval between the date of inclusion and the date of death
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| No statistical analyses for this end point | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Any AE occurring during study AND within 12 months after the last administration of CdA, and within 3 months of the last administration of VPA, have been reported on the AE form of the CRF, regardless of its relationship to study. Any AE was documented an
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Adverse event reporting additional description |
Any type of adverse event possibly linked to the IMP will be collected at each visit and graded according to NCIC-CTC version 3.0.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
CTCAE GRADE | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
3.0
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Reporting groups
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Reporting group title |
Valproic acid combined with CdA
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Reporting group description |
Patients receiving VPA / 5/mg /kg twice a day, per os and CdA / 5,6 mg/m²/day during 3 days, every 28 days, IV, for 4 cycles | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||||||
Interruptions (globally) |
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| Were there any global interruptions to the trial? Yes | |||||||
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Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||||||
| None reported | |||||||
