Myelodysplastic Syndrome MDSPhase 2VALENANCT00977132
Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome
A Phase 2 study testing Valproic aicd and Lenalidomide in people with Myelodysplastic Syndrome MDS, run by Heinrich-Heine University, Duesseldorf at 6 sites in Germany.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Myelodysplastic Syndrome MDS
- What is being tested?
- Valproic aicd and Lenalidomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 6 sitesGermany
- Study dates
- Oct 2009to May 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Cytologically/histologically confirmed primary myelodysplastic syndrome (pMDS) with a favorable risk profile, i.e., low or intermediate I risk group according to IPSS (<10% blasts, no unfavorable karyotype)
- platelet count ≥50.000/µl
- absolute neutrophil count ≥1.000/µl
- age ≥18 years at the time of signing the informed consent form
- Karnofsky performance status > 50%
- written informed consent to participate
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- erythropoietin level > 200 mU/ml or failure of previous therapy with erythropoietin
- patients in whom allogeneic bone marrow transplantation, treatment with growth factors or immune therapy is not possible due to medical or biologic reasons or patients in whom such a therapy would be possible but who do not agree to such a therapy for personal reasons
- females of childbearing potential (FCBP, see page 23) must agree to one reliable form of contraception or to practice complete abstinence from heterosexual intercourse during the following time periods related to this study: 1) for at least 4 weeks before starting study drug; 2) while participating in the study, even during treatment interruptions; and 3) for at least 4 weeks after discontinuation from the study.
Who cannot join
- patients with 5q deletion
- MDS treated with experimental therapy or chemotherapy within 4 weeks prior to start of treatment with study drugs
- previous treatment of MDS with valproic acid or lenalidomide as monotherapy patients suitable for chemotherapy, therapy with growth factors or allogeneic bone marrow transplantation and who are willing to start such a therapy
- hypersensitivity to thalidomide
- insufficient liver function (bilirubin, AST or ALT > 2 x ULN)
- hepatic disease [details see full protocol]
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- markedly impaired renal function (serum creatinine > 2mg/dl)
- pregnancy, breast feeding, lactation, refusal to use safe contraceptive methods during the study
- psychiatric disease or addiction with impaired ability to act and make decisions according to one's free will
- participation in another interventional study 4 weeks prior to or during this study
- known hypersensitivity or allergies to one of the study drugs or their ingredients
- plasmatic coagulation disorder
Trial locations and contacts
6 sites in 1 country.
6 sites in 1 country
Germany6 sites
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
Dresden, Saxony, 01307
St. Johannes Hospital Duisburg
Duisburg, North Rhine-Westphalia, 47166
Heinrich-Heine-University Duesseldorf, Department of Hematology, Oncology and Clinical Immunology
Düsseldorf, North Rhine-Westphalia, 40225
Medizinische Universitätsklinik Freiburg, Abteilung Innere Medizini
Freiburg im Breisgau, Baden Würtemberg, 79106
Georg-August-Universität,Universitätsklinikum - Abteilung Hämatologie und Onkologie
Göttingen, Lower Saxony, 37075
Universitätsklinikum Ulm, Klinik für Innere Medizin III
Ulm, Bavaria, 89081
About this study
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
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.
Read the detailed description
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
- Conditions
- Myelodysplastic Syndrome MDS
- Being tested
- Valproic aicd, Lenalidomide
- Keywords
- Myelodysplastic Syndromes, Valproic acid, Lenalidomide
- Medical subject headings
- Anemia, Refractory, with Excess of Blasts, Myelodysplastic Syndromes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Valproic aicdDrug
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.
LenalidomideDrug
Also called Revlimid
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
| Study group | Role | What they receive |
|---|---|---|
| Lenalidomide | Experimental | Lenalidomid in combination valproic acid Receives: Drug: Valproic aicd; Drug: Lenalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
hematologic success
Measured: 5 years
Secondary outcomes (3)
toxicity and safety
Measured: 5 years
Progression free survival
Measured: 5 years
overall survival
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2009 (estimated)
- Study startOct 2009
- Primary completionMay 2013
- Study completionMay 2014
Why it stopped: delayed recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Myelodysplastic Syndrome MDSStudies of the same condition, open and under way.
- More trials run by Heinrich-Heine University, DuesseldorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Heinrich-Heine University, Duesseldorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Norbert Gattermann, Professor, Study director, Department of Hematology, Oncology and Clinical Immunology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00977132
- Sponsor's protocol ID
- Valena-Study
- Acronym
- VALENA
- Status last verified
- Mar 2015
- First submitted
- 14 Sep 2009
- Last updated
- 18 Mar 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00977132
- Acronym / sponsor ID
- VALENA / Valena-Study
- Conditions
- Myelodysplastic Syndrome MDS
- Keywords
- Myelodysplastic Syndromes, Valproic acid, Lenalidomide
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: delayed recruitment
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Heinrich-Heine University, DuesseldorfUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- May 2013 (actual)
- Study completion
- May 2014 (actual)
- First posted
- 15 Sep 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Lenalidomide | Experimental | Drug: Valproic aicd, Drug: LenalidomideLenalidomid in combination valproic acid |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Cytologically/histologically confirmed primary myelodysplastic syndrome (pMDS) with a favorable risk profile, i.e., low or intermediate I risk group according to IPSS (<10% blasts, no unfavorable karyotype)
- platelet count ≥50.000/µl
- absolute neutrophil count ≥1.000/µl
- age ≥18 years at the time of signing the informed consent form
- Karnofsky performance status > 50%
Key exclusion criteria (12 listed)
- patients with 5q deletion
- MDS treated with experimental therapy or chemotherapy within 4 weeks prior to start of treatment with study drugs
- previous treatment of MDS with valproic acid or lenalidomide as monotherapy patients suitable for chemotherapy, therapy with growth factors or allogeneic bone marrow transplantation and who are willing to start such a therapy
- hypersensitivity to thalidomide
- insufficient liver function (bilirubin, AST or ALT > 2 x ULN)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valproic aicdTreatment 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. | Drug | Lenalidomide |
| LenalidomideAlso: Revlimid5 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 | Drug | Lenalidomide |
Primary outcome
hematologic success
Time frame: 5 years
3 secondary outcomes
toxicity and safety
Time frame: 5 years
Progression free survival
Time frame: 5 years
overall survival
Time frame: 5 years
Results and safety
The study was stopped early (reason given: delayed recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Mar 2015.
Related trials for Myelodysplastic Syndrome MDS
Active, not recruitingPhase 1/2
Omacetaxine + Azacitidine in Untreated Patients With High Grade MDS
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RecruitingPhase 1/2
Pacritinib, a Kinase Inhibitor of CSF1R, IRAK1, JAK2, and FLT3, in Adults and Pediatric Participants 12 Years of Age or Older With Myelodysplastic Syndromes or Myelodysplastic/Myeloproliferative Neoplasms
Myelodysplastic Syndromes
Active, not recruitingPhase 2
Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia
Adult Acute Lymphoblastic Leukemia in Remission, Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome
Not yet recruitingPhase 1
ATRN-119 in Combination With Decitabine in Patients With TP53-Mutated AML or Higher-Risk MDS
Acute Myeloid Leukemia, High-risk Myelodysplastic Syndrome
RecruitingPhase 1/2
Study of R289 in Patients With Lower-risk Myelodysplastic Syndromes (LR MDS)
Low Risk Myelodysplastic Syndromes
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Norbert Gattermann, Professor study director
Department of Hematology, Oncology and Clinical Immunology
6 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Valproic aicd and Lenalidomide in people with Myelodysplastic Syndrome MDS, run by Heinrich-Heine University, Duesseldorf at 6 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 18 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 6 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: delayed recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
hematologic success (time frame: 5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2015.