A Single-Arm, Open-Label Study of the Efficacy and Safety of Lenalidomide in Combination With Cyclosporine A in Patients With Red Blood Cell Transfusion-Dependent Myelodysplastic Syndromes
- Understand and voluntarily sign an informed consent form.
- Age ≥ 18 years at the time of signing the informed consent form.
- Able to adhere to the study visit schedule and other protocol requirements.
- Diagnosis of low or intermediate-1 risk IPSS (MDS without an abnormality of
chromosome 5 involving a deletion between bands q31 and q33. Red blood cell (RBC)
transfusion-dependent anemia as having received ≥ 2 units of RBCs within 8 weeks on
the first day of study treatment.
- ECOG performance status of ≤ 2 at study entry
- Laboratory test results within the following ranges:
- Absolute neutrophil count (ANC) >500 x 109/L
- Platelet count ≥ 50 x 109/L
- Serum creatinine ≤ 2.0 mg/dL
- Total bilirubin ≤ 1.5 mg/dL
- AST (SGOT) and ALT (SGPT) ≤ 2 x ULN
- Disease free of prior malignancies for ≥ 5 years with exception of currently treated
basal cell, squamous cell carcinoma of the skin, or carcinoma "insitu" of the cervix
- All study participants must be registered into the mandatory RevAssist® program, and
be willing and able to comply with the requirements of RevAssist®.
- Females of childbearing potential (FCBP) must have a negative serum or urine
pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to
and again within 24 hours of prescribing lenalidomide (prescriptions must be filled
within 7 days) and must either commit to continued abstinence from heterosexual
intercourse or begin TWO acceptable methods of birth control, one highly effective
method and one additional effective method AT THE SAME TIME, at least 28 days before
she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing.
Men must also agree to use a latex condom during sexual contact with a FCBP even if
they have had a successful vasectomy.
- Able to take asprin (81 or 325 mg) daily as a prophylactic anticoagulation (patients
intolerant to ASA may use warfarin or low molecular weight heparin).
- Any serious medical condition, laboratory abnormality, or psychiatric illness that
would prevent the subject from signing the informed consent form.
- Pregnant or breast feeding females. (Lactating females must agree not to breast feed
while taking lenalidomide).
- Any condition, including the presence of laboratory abnormalities, which places the
subject at unacceptable risk if he/she were to participate in the study or confounds
the ability to interpret data from the study.
- Use of any other experimental drug or therapy within 28 days of baseline.
- Known hypersensitivity to thalidomide. Prior ≥ grade 3 NCI CTCAE (Version 3.0)
- The development of erythema nodosum if characterized by a desquamating rash while
taking thalidomide or similar drugs.
- Any prior use of lenalidomide.
- Concurrent use of other anti-cancer agents or treatments.
- Known positive for HIV or infectious hepatitis, type A, B, or C.
- Inability to aspirate bone marrow (dry tap).
- Proliferative (WBC ≥ 12,000/ul) CMML
- An abnormality of chromosome 5 involving a deletion between bands q31 and q 33.
- Any of the following lab abnormalities:
- Absolute neutrophil count (ANC) <500 cells/mm3 (0.5 x 109/L)
- Platelet count ≤ 50,000/mm3 (50 x 109/L)
- Serum creatinine ≥ 2.5 mg/dL (221µmol/L)
- Serum SGOT/AST or SGPT/ALT ≥ 2.0 x upper limit of normal (ULN)
- Serum direct bilirubin ≥ 2.0 mg/dL (34µmol/L)
- Clinically significant anemia due to factors such as iron, B12 or folate
deficiencies, autoimmune or hereditary hemolysis or gastrointestinal bleeding (if a
marrow aspirate is not evaluable for storage iron, transferring saturation must be ≥
20% and serum ferritin not less than 50ng/mL).
- Use of hematopoietic growth factors within 7 days of the first day of study drug
- Chronic use (≥2 weeks) of greater than physiologic doses of a corticosteroid agent
(dose equivalent to ≥ 10mg/day of prednisone) within 28 days of the first study drug
- Use of experimental or standard drug (i.e chemotherapeutic, immunosuppressive,
cytoprotective agents) for the treatment of MDS within 28 days of the first day of
- Prior history of malignancy other than MDS except basal cell or squamous cell
carcinoma in situ of the cervix or breast, unless the patient has been free of
disease for ≥ 5 year.
- Myocardial infarction within 6 months prior to enrollment, or NYHA (New York
Hospital Association) Class III or IV heart failure disease. History of active
angina, congestive heart disease, uncontrolled angina, severe uncontrolled
ventricular arrhythmias, electrocardiographic evidence of uncontrolled ischemia
and/or active conduction system abnormalities, or myocardial infarction within 6
months prior to enrollment, acute ischemia, or active conduction system
- Active viral or bacterial infections or any coexisting medical problem that would
significantly increase the risks of this treatment program.
- History of thromboembolic event within the past 6 months prior to enrollment.
- Patients who have a hypersensitivity to Sandimmune® (cyclosporine).