A Trial of Lenalidomide & Azacitidine in Low Risk Myelodysplastic Syndromes

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

1. Understand and voluntarily sign an informed consent form.
2. Age 18 years at the time of signing the informed consent form.
3. Able to adhere to the study visit schedule and other protocol requirements.
4. Diagnosis of low- or intermediate-1-risk IPSS (see Appendix III) MDS without an abnormality of chromosome 5 involving a deletion between bands q31 and q33.

   Pathologic diagnosis via pathology performed at Rush University Medical Center or made available to Rush from outside institution.
5. Prior treatment with \< 3 cycles (84 days) of Revlimid® (lenalidomide) are eligible for enrollment regardless of response.
6. ECOG performance status of 2 at study entry (see Appendix II).
7. 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.
8. 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.
9. Serum glutamic-oxaloacetic transaminase (SGOT) (aspartate aminotransferase \[AST\]) or serum glutamic-pyruvic transaminase (SGPT) (alanine aminotransferase \[ALT\]) levels \< 2 x ULN.
10. Serum creatinine levels \< 1.5 x ULN
11. Absolute neutrophil count \> 1000/mm³
12. Platelet count \> 30,000/mm³
13. All study participants must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®.

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.