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

NCT00977132 | Terminated Phase 2 DMC

• 1 other identifier: Valena-Study
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

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.

Conditions

Myelodysplastic Syndrome MDS

Keywords

Myelodysplastic Syndromes; Valproic acid; Lenalidomide

Outcome Measures

Primary Outcomes (1)

• hematologic success

  5 years

Secondary Outcomes (3)

• toxicity and safety

  5 years

• Progression free survival

  5 years

• overall survival

  5 years

Study Arms (1)

Lenalidomide

EXPERIMENTAL

Lenalidomid in combination valproic acid

Drug: Valproic aicd; Drug: Lenalidomide

Interventions

Valproic aicd DRUG

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.

Lenalidomide

Lenalidomide DRUG

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

Also known as: Revlimid

Lenalidomide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Heinrich-Heine University, Duesseldorf: lead

Study Sites (6)

Medizinische Universitätsklinik Freiburg, Abteilung Innere Medizini

Freiburg im Breisgau, Baden Würtemberg, 79106, Germany

Location

Universitätsklinikum Ulm, Klinik für Innere Medizin III

Ulm, Bavaria, 89081, Germany

Location

Georg-August-Universität,Universitätsklinikum - Abteilung Hämatologie und Onkologie

Göttingen, Lower Saxony, 37075, Germany

Location

St. Johannes Hospital Duisburg

Duisburg, North Rhine-Westphalia, 47166, Germany

Location

Heinrich-Heine-University Duesseldorf, Department of Hematology, Oncology and Clinical Immunology

Düsseldorf, North Rhine-Westphalia, 40225, Germany

Location

Universitätsklinikum Carl Gustav Carus an der TU Dresden, Medizinische Klinik und Poliklinik I

Dresden, Saxony, 01307, Germany

Location

MeSH Terms

Conditions

Anemia, Refractory, with Excess of Blasts; Myelodysplastic Syndromes

Interventions

Lenalidomide

Condition Hierarchy (Ancestors)

Anemia, Refractory; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Norbert Gattermann, Professor

  Department of Hematology, Oncology and Clinical Immunology

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2009
• First Posted: September 15, 2009
• Study Start: October 1, 2009
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2014
• Last Updated: March 18, 2015

Record last verified: 2015-03

Locations

DE (6)