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

This study has been terminated.
(delayed recruitment)
Sponsor:
Information provided by (Responsible Party):
Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier:
NCT00977132
First received: September 14, 2009
Last updated: January 29, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
Myelodysplastic Syndrome MDS
Drug: Valproic aicd
Drug: Lenalidomide
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Heinrich-Heine University, Duesseldorf:

Primary Outcome Measures:
  • hematologic success [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 23
Study Start Date: October 2009
Estimated Study Completion Date: May 2014
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide
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.

Drug: Lenalidomide

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

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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00977132

Locations
Germany
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
Sponsors and Collaborators
Heinrich-Heine University, Duesseldorf
Investigators
Study Director: Norbert Gattermann, Professor Department of Hematology, Oncology and Clinical Immunology
  More Information

No publications provided

Responsible Party: Heinrich-Heine University, Duesseldorf
ClinicalTrials.gov Identifier: NCT00977132     History of Changes
Other Study ID Numbers: Valena-Study
Study First Received: September 14, 2009
Last Updated: January 29, 2014
Health Authority: Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Heinrich-Heine University, Duesseldorf:
Myelodysplastic Syndromes
Valproic acid
Lenalidomide

Additional relevant MeSH terms:
Myelodysplastic Syndromes
Preleukemia
Bone Marrow Diseases
Hematologic Diseases
Precancerous Conditions
Neoplasms
Valproic Acid
Lenalidomide
Thalidomide
Anticonvulsants
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
GABA Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Antimanic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Immunologic Factors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents

ClinicalTrials.gov processed this record on August 20, 2014