Phase I/II Study of the Combination of 5-azacitidine with Lenalidomide in Patients with High Risk Myelodysplastic Syndrome (MDS) and Acute Myelogenous Leukemia (AML)
The goal of Phase 1 of this clinical research study is to find the highest tolerable dose of lenalidomide that can be given in combination with azacitidine to patients with MDS or AML. The goal of Phase 2 of this study is to learn if the combination dose of azacitidine and lenalidomide found in Phase 1 can help to control MDS and/or AML. The safety of this drug combination will be studied in both Phases.
Disease Group: Leukemia
Treatment Agent: 5-Azacytidine,Lenalidomide
Treatment Location: Only at MD Anderson
Estimatated Length of Stay in Houston: All patients will be registered through CORe. All 5-azacytidine courses will ;be given at M.D. Anderson Cancer Center, either as in-patient or out-patient. ;
Sponsor: Celgene Corporation
Return Visit: Weekly
Home Care: Lenalidomide will be self-administered
1. To determine the maximal tolerated dose of lenalidomide in combination with 5-azacytidine (5-aza) in patients with leukemia. 2. To determine the clinical activity of the combination of 5-azacytdine and lenalidomide in patients with AML and MDS. 3. To determine the in vivo molecular and biological effects of this combination. These will include analysis of changes in DNA methylation, histone modifications, and gene expression.
IRB Review and Approval Date: 11/25/2009
Recruitment Status: Not Accepting
Projected Accrual: N/A
1) Patients with higher risk MDS (bone marrow blasts >/= 10% to 30%
inclusive) of any age who refuse or are not eligible for frontline chemotherapy.
2) No prior therapy for higher risk MDS as defined above.
3) Performance status of </= 2 by the ECOG scale.
4) Signed informed consent indicating that patients are aware of the investigational nature of this study in keeping with the policies of UTMDACC.
5) Hydroxyurea for patients with rapidly proliferative disease can be used up to 24 hours prior to therapy but not concomitantly with 5-azacitidine or lenalidomide. Hydroxyurea can be used once the patient has completed the planned 5 axacitidine and lenalidomide treatment.
6) Adequate liver function: Total bilirubin of </= 1.5 x ULN, AST (SGOT) and ALT (SGPT) </= 3 x ULN
7) Renal function - assessed by calculated creatinine clearance as follows (see Appendix: Cockcroft-Gault estimation of CrCl): 1. Phase I subjects must have calculated creatinine clearance >/= 60ml/min by Cockcroft-Gault formula. 2. Phase II subjects must have calculated creatinine clearance >/= 30ml/min by Cockcroft-Gault formula.
8) All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS®.
9) Females of reproductive potential must adhere to the scheduled pregnancy testing as required in the Revlimid REMS® program.
10) Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin).
11) 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.
12) Continued from #9: Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy.
1) Nursing and pregnant females.
2) Known or suspected hypersensitivity to azacitidine or mannitol.
3) Patients with advanced malignant hepatic tumors.
4) Unwilling or unable to remain in compliance with the RevAssist® program
5) Known hypersensitivity to thalidomide or lenalidomide (if applicable).
6) The development of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs.
7) Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible.
Information and next steps
Phase I/Phase II
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