A Trial of Lenalidomide & Azacitidine in Low Risk Myelodysplastic Syndromes
Condition: MDS
MeSH terms: Preleukemia; Myelodysplastic Syndromes
Intervention: Lenalidomide and azacitidine combination
Intervention description: lenalidomide 10 mg will be administered orally on Days 1-28 of each 28-day cycle. Patients who fail to achieve an erythroid response per 2006 IWG criteria after 3 cycles of monotherapy will receive lenalidomide at the same dose administered in cycle 3 and low-dose azacitidine25 mg/m2 subcutaneously (SC) or intravenously (IV) for 5 days (on Days 1-5) of every 28-day cycle.
Patients who fail to respond (2006 IWG criteria) after receiving two cycles of combination therapy will receive lenalidomide at the same dose administered in Cycle 3 and azacitidine 50 mg/m2 SC or IV given daily on Days 1-5 of each 28-day cycle, if no grade 4 toxicity developed or no delay greater than 2 weeks in starting a new cycle was experienced during the first 2 cycles of combination therapy.
Intervention MeSH terms: Lenalidomide; Azacitidine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 2.0
Sex: All
Minimum age: 18 Years
Maximum age: 90 Years
Healthy volunteers: No
Keywords: MDS; Low risk disease; IPSS

Summary:

      This phase II study will evaluate the safety and efficacy of combining two active
      agents;Revlimid® (lenalidomide) and low dose Vidaza® (azacitidine) for the treatment of
      patients with low to intermediate-1 MDS excluding patients with 5 q deletion. The rationale
      for adding Vidaza® (azacitidine) after 3 months of revlimid monotherapy is that combination
      therapy will result in higher response rates, and potentially longer response duration than
      that achieved with either agent.

      STUDY OBJECTIVES:

      Primary:

      To determine the safety and tolerability of the combination of Revlimid® (lenalidomide) and
      low dose Vidaza® (azacitidine) in patients with low - intermediate-1 risk MDS non 5 q
      deletion who have not responded after 3 months of Revlimid® (lenalidomide) monotherapy

      Secondary:

      To determine the response rate in patients with low - intermediate-1 risk MDS non 5 q
      deletion receiving Revlimid® (lenalidomide) in combination with low dose Vidaza®
      (azacitidine), as defined by the IWG 2006 Revised Response Criteria
    

Eligibility criteria:

        Inclusion Criteria: Patients with low to Int-1 risk MDS

          1. ECOG performance status of < 2 at study entry (see Appendix II).

          2. 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
             or breast.

          3. Serum bilirubin levels < 1.5 times the upper limit of the normal range for the
             laboratory (ULN). Higher levels are acceptable if these can be attributed to active
             hemolysis or ineffective erythropoiesis.

          4. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase [AST]) or
             serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase [ALT]) levels < 2
             x ULN.

          5. Serum creatinine levels 1.5 x ULN

          6. Absolute neutrophil count > 1000/mm³

          7. Platelet count > 30,000/mm³

          8. All study participants must be registered into the mandatory RevAssist® program, and
             be willing and able to comply with the requirements of RevAssist®.

          9. Females of childbearing potential (FCBP)† must have a negative serum or urine

        Exclusion Criteria:

          1. Any serious medical condition, laboratory abnormality, or psychiatric illness that
             would prevent the subject from signing the informed consent form.

          2. Pregnant or breast feeding females. Lactating females must agree not to breast feed
             while taking Revlimid® (lenalidomide).

          3. 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.

          4. Use of any other experimental drug or therapy within 28 days of baseline.

          5. Known hypersensitivity to lenalidomide, azacitidine, or mannitol.

          6. Any prior use of Vidaza® (azacitidine).

          7. Prior use of Revlimid® (lenalidomide) for more than 84 days (three 28 day cycles).

          8. Concurrent use of other anti-cancer agents or treatments.

          9. Known positive for HIV or infectious hepatitis, type B or C.