search
Back to results

Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome (VALENA)

Primary Purpose

Myelodysplastic Syndrome MDS

Status
Terminated
Phase
Phase 2
Locations
Germany
Study Type
Interventional
Intervention
Valproic aicd
Lenalidomide
Sponsored by
Heinrich-Heine University, Duesseldorf
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndrome MDS focused on measuring Myelodysplastic Syndromes, Valproic acid, Lenalidomide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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
  • 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.

Exclusion Criteria:

  • 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]
  • 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

Sites / Locations

  • Medizinische Universitätsklinik Freiburg, Abteilung Innere Medizini
  • Universitätsklinikum Ulm, Klinik für Innere Medizin III
  • Georg-August-Universität,Universitätsklinikum - Abteilung Hämatologie und Onkologie
  • Heinrich-Heine-University Duesseldorf, Department of Hematology, Oncology and Clinical Immunology
  • St. Johannes Hospital Duisburg
  • Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Lenalidomide

Arm Description

Lenalidomid in combination valproic acid

Outcomes

Primary Outcome Measures

hematologic success

Secondary Outcome Measures

toxicity and safety
Progression free survival
overall survival

Full Information

First Posted
September 14, 2009
Last Updated
March 17, 2015
Sponsor
Heinrich-Heine University, Duesseldorf
search

1. Study Identification

Unique Protocol Identification Number
NCT00977132
Brief Title
Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome
Acronym
VALENA
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2015
Overall Recruitment Status
Terminated
Why Stopped
delayed recruitment
Study Start Date
October 2009 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Heinrich-Heine University, Duesseldorf

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndrome MDS
Keywords
Myelodysplastic Syndromes, Valproic acid, Lenalidomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
23 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lenalidomide
Arm Type
Experimental
Arm Description
Lenalidomid in combination valproic acid
Intervention Type
Drug
Intervention Name(s)
Valproic aicd
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Lenalidomide
Other Intervention Name(s)
Revlimid
Intervention Description
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
Primary Outcome Measure Information:
Title
hematologic success
Time Frame
5 years
Secondary Outcome Measure Information:
Title
toxicity and safety
Time Frame
5 years
Title
Progression free survival
Time Frame
5 years
Title
overall survival
Time Frame
5 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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. Exclusion Criteria: 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] 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Norbert Gattermann, Professor
Organizational Affiliation
Department of Hematology, Oncology and Clinical Immunology
Official's Role
Study Director
Facility Information:
Facility Name
Medizinische Universitätsklinik Freiburg, Abteilung Innere Medizini
City
Freiburg
State/Province
Baden Würtemberg
ZIP/Postal Code
79106
Country
Germany
Facility Name
Universitätsklinikum Ulm, Klinik für Innere Medizin III
City
Ulm
State/Province
Bayern
ZIP/Postal Code
89081
Country
Germany
Facility Name
Georg-August-Universität,Universitätsklinikum - Abteilung Hämatologie und Onkologie
City
Goettingen
State/Province
Niedersachsen
ZIP/Postal Code
37075
Country
Germany
Facility Name
Heinrich-Heine-University Duesseldorf, Department of Hematology, Oncology and Clinical Immunology
City
Duesseldorf
State/Province
NRW
ZIP/Postal Code
40225
Country
Germany
Facility Name
St. Johannes Hospital Duisburg
City
Duisburg
State/Province
NRW
ZIP/Postal Code
47166
Country
Germany
Facility Name
Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I
City
Dresden
State/Province
Sachsen
ZIP/Postal Code
01307
Country
Germany

12. IPD Sharing Statement

Learn more about this trial

Efficacy and Tolerability of the Combination of Valproic Acid and Lenalidomide in the Treatment of Patients With Myelodysplastic Syndrome

We'll reach out to this number within 24 hrs