A Multicentre Open Randomized Phase II Study of the Efficacy and Safety of Azacitidine Alone or in Combination With Lenalidomide in High-risk Myeloid Disease (High-risk Myelodysplastic Syndrome and Acute Myeloid Leukemia) With a Karyotype Including Del(5q)
This is an prospective open multi-center randomized phase II study of standard dose
azacytidine with or without the addition of lenalidomide in high-risk myeloid disease
(high-risk MDS and AML) with a karyotype including del(5q). Seventy-two patients, eligible
for treatment with azacytidine (Intermedium/INT-2 and High-risk MDS and AML with 20-30 %
marrow blasts according to label) will be included.
Azacytidine will be given in a modified standard dose, azacytidine 5+2 (75 mg/m2/ d
subcutaneously for 5 days, followed by a 2-day weekend break, followed by azacytidine 75
mg/m2/ d for 2 days every 28 days, no individual dose exceeding 200 mg) for 6 cycles. Cycle
interval may be prolonged if toxicity according to predefined criteria occurs. Patients will
be randomized to azacytidine (Arm A) or azacytidine + lenalidomide (Arm B). The initial dose
of lenalidomide is 10 mg 21/28 days, starting day 1 in each azacytidine cycle and leaving
the last week before start of next azacytidine cycle free. The dose should be increased to
20 mg day 1 in cycle 4 if no toxicity according to predefined criteria occurs. The total
study period is 24 weeks + additional weeks caused by prolonged cycle interval. Patients,
who following a response may be eligible for allo-SCT may exit the study after cycle 3, 4 or
5 and then be subject to end-of-study assessment. Patients who at start of treatment, or any
time during study have a neutrophil count <0,5 x 109/l will be treated with
Granulocyte-ColonyStimulatingFactor (G-CSF).
Interventional
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Response according to IWG criteria for MDS and AML
Response according to IWG criteria include hematologic response (including transfusion independence), bone marrow response (blast count) and cytogenetic response (karyotype) after 6 cycles of azacytidine or azacytidine+lenalidomide. For patients who can keep the 4 week interval the Time Frame will be 25 weeks. The cycle interval can be extended up to 8 weeks which makes 44 weeks the maximum Time Frame.
25-44 weeks (after 6 cycles of azacitidine or azacitidine+lenalidomide)
No
Lars Möllgård, MD, PhD
Principal Investigator
Nordic MDS Group
Sweden: Medical Products Agency
NMDSG10B
NCT01556477
March 2012
November 2014
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