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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

Phase 2
18 Years
Not Enrolling
Myelodysplastic Syndrome MDS

Thank you

Trial Information

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

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

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

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

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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

hematologic success

Outcome Time Frame:

5 years

Safety Issue:


Principal Investigator

Norbert Gattermann, Professor

Investigator Role:

Study Director

Investigator Affiliation:

Department of Hematology, Oncology and Clinical Immunology


Germany: Federal Institute for Drugs and Medical Devices

Study ID:




Start Date:

October 2009

Completion Date:

December 2013

Related Keywords:

  • Myelodysplastic Syndrome MDS
  • Myelodysplastic Syndromes
  • Valproic acid
  • Lenalidomide
  • Myelodysplastic Syndromes
  • Preleukemia