Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome (VALENA)
As part of a palliative therapy concept, feasibility, toxicity, and effectiveness of treatment with the combination of Valproic acid and lenalidomide in Myelodysplastic Syndrome patients with a favorable risk profile will be investigated.
Myelodysplastic Syndrome MDS
Drug: Valproic aicd
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study for the Determination of Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome With Favorable Risk Profile|
- hematologic success [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- toxicity and safety [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
- Progression free survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
- overall survival [ Time Frame: 5 years ] [ Designated as safety issue: No ]
|Study Start Date:||October 2009|
|Estimated Study Completion Date:||May 2014|
|Primary Completion Date:||May 2013 (Final data collection date for primary outcome measure)|
Lenalidomid in combination valproic acid
Drug: Valproic aicd
Treatment with VPA starts at day1, the dose ist slowly increase according to the following scheme
day morning dose midday dose evening dose contents of 1 tablet
1+2 0 0 1 500 mg
3+4 ½ 0 1 500 mg
5+6 1 0 1 500 mg
7+8 1 ½ 1 500 mg
9+10 1 1 1 500 mg
11+12 1 1 1 500 mg
In the morning of day 13 trough level of VPA will be checked. The target range will be 50-110 µg/l. The dose of VPA will be adjusted depending on the trough level. In the first eight weeks of therapy weekly controls of VPA levels are required. Thereafter, VPA levels will be checked every four weeks.
5 mg/day, continuous therapy
Dosing will be in the morning at approximately the same time each day. Capsules may be taken before or after a meal.
Only one cycle of study drug (28 days) will be supplied to the patient every four weeks
Other Name: Revlimid
Treatment will be administered as continuous therapy, i.e. it should be taken on each day as described below without treatment interruption as long as no criteria for termination of treatment are met. After two years the primary endpoint will be evaluated. Non-responders will be taken off study after 4 months of therapy. Patients who relapse after an initial response to study treatment can receive one attempt to re-start therapy after a short duration of discontinuation.
Treatment with Valproic Acid starts at day 1. The dose of Valproic Acid is slowly increased. In the morning of day 13 trough level of Valproic Acid will be checked. The target range will be 50-110 µg/l. The dose of Valproic Acid will be adjusted depending on the trough level.
In the first eight weeks of therapy weekly controls of Valproic Acid levels are required. Thereafter, Valproic Acid levels will be checked every four weeks.
The planned dose of lenalidomide is 10 mg/day, orally as continuous therapy. Dosing will be in the morning at approximately the same time each day. Capsules may be taken before or after a meal. In the course of the study the dose will be adjusted to the results of the blood count.
Only one cycle of study drug (28 days) will be supplied to the patient every four weeks.
Patients experiencing adverse events may need study treatment modifications.
During treatment with study medication weekly control visits for the detection of adverse events are required during the first eight weeks, thereafter the patient must be seen every four weeks.
Therapeutic success is evaluated in 4-weekly intervals. Bone marrow will be examined after 12 weeks and after 48 weeks or in case of premature study termination
|Medizinische Universitätsklinik Freiburg, Abteilung Innere Medizini|
|Freiburg, Baden Würtemberg, Germany, 79106|
|Universitätsklinikum Ulm, Klinik für Innere Medizin III|
|Ulm, Bayern, Germany, 89081|
|Georg-August-Universität,Universitätsklinikum - Abteilung Hämatologie und Onkologie|
|Goettingen, Niedersachsen, Germany, 37075|
|Heinrich-Heine-University Duesseldorf, Department of Hematology, Oncology and Clinical Immunology|
|Duesseldorf, NRW, Germany, 40225|
|St. Johannes Hospital Duisburg|
|Duisburg, NRW, Germany, 47166|
|Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I|
|Dresden, Sachsen, Germany, 01307|
|Study Director:||Norbert Gattermann, Professor||Department of Hematology, Oncology and Clinical Immunology|