Phase II Randomized Study of Lower Doses of Decitabine (DAC; 20 mg/m² IV daily for 3 days every month) versus Azacitidine (AZA; 75 mg/m² SC/IV daily for 3 days every month) versus Azacitidine (AZA; 75 mg/m² SC/IV daily for 5 days every month) in MDS Patients with Low and Intermediate-1 Risk Disease Transfusion-Dependent versus Best Supportive Care (BSC) in MDS Patients with Low and Intermediate-1 Risk Disease Transfusion-Independent
Johns Hopkins Kimmel Cancer Center in Baltimore
Compare the event-free survival of two different drugs: DAC versus AZA on an abbreviated schedule to a standard arm of AZA given over 5 days in patients with low-risk MDS transfusion-dependent and to BSC in patients with low-risk MDS transfusion-independent.
-Age equal to 18 years-de novo or secondary, IPSS low- or intermediate-1 risk MDS, including CMML-1-ECOG performance status of equal to 3 at study entry-Organ function as defined below: -Serum creatinine equal to 2 mg/dL -Total bilirubin equal to 2 x ULN -ALT (SGPT) equal to 2 x ULN -AST (SGOT) equal to 2 x ULN-Women of childbearing potential must have a negative serum or urine pregnancy test within 7 days and will also need to use contraceptives. Men must agree not to father a child and agree to use a condom if his partner is of child bearing potential.-Breast feeding females are excluded.-Prior therapy with decitabine or azacitidine is not allowed.
Transfusion-dependent subjects will be randomized to AZA 75 mg/m2 IV/SC for 5 days, AZA 75 mg/m2 IV/SC for 3 days, or DAC 20 mg/m2 IV for 3 days on an even basis at the beginning, then, based on efficacy and following a Bayesian design, patients will be assigned to the superior arm. Transfusion-independent subjects will be randomized to either BSC or one of the 3 arms mentioned above on an even basis at the beginning, then, based on efficacy and following a Bayesian design, patients will be assigned to the superior arm.Transfusion-independent subjects assigned to BSC will be assigned to one of the 3 above arms once they start requiring blood transfusion. That would be considered an event. Transfusion-dependent group will be defined as patients requiring blood transfusion at any time. Patients will be randomized to receive:Decitabine 20 mg/m2 IV daily for 3 days (days 1-3) approximately every 28 daysorAzacitidine 75 mg/m2 SC or IV daily for 3 days (days 1-3) approximately every 28 daysorAzacitidine 75 mg/m2 SC or IV daily for 5 days (days 1-5) approximately every 28 daysorBSC (for transfusion-independent subjects only)Patients may receive their second course of therapy without interruption, regardless of their degree of myelosuppression. After the first course of therapy, the interval between subsequent cycles of therapy could be shortened or prolonged at the discretion of the investigator. Subsequent cycles can be given prior to peripheral blood count recovery if considered to be in the best interest for the patient and after discussion with the principal investigator and the discussion documented in the patient’s medical record.
03/05/2019 05:03 AM