Revlimid®, and Metronomic Melphalan in the Management of Higher Risk Myelodysplastic Syndromes (MDS) and CMML: a Phase 2 Study"
1. Determine the overall response rates of low dose melphalan used in combination with
lenalidomide in higher risk MDS
1. Determine the frequency of hematologic improvement of low dose melphalan used in
combination with lenalidomide in higher risk MDS·
2. Determine the safety and tolerability of low dose melphalan used in combination with
lenalidomide in higher risk MDS·
3. Determine the effects of low dose melphalan used in combination with lenalidomide on
biomarkers of angiogenesis in higher risk MDS·
4. Determine the frequency of cytogenetic remissions of low dose melphalan used in
combination with lenalidomide in higher risk MDS
This study is a single center, open-label, non-randomized Phase II study. Patients with
higher risk MDS are included. This patient population will be defined by either high
intermediate or high risk IPSS scores or proliferative CMML with symptomatic cytopenias or
hypersplenism (IPSS score does not apply). If cytogenetics are unavailable, patients with
transfusion dependent RAEB-1 will be eligible.
This is an open label, single center non-randomized Phase II study of melphalan 2 mg po and
lenalidomide, 10 mg po daily on days 1 - 21 of a 28 day cycle in adult patients with higher
risk MDS. Patients may continue to receive drug for a maximum of 12 months or until one of
the following occur: death; disease progression (for definition, see appendix D);
intercurrent illness that prevents further administration of treatment; unacceptable adverse
event(s); patient decides to withdraw from the study; or if general or specific changes in
the patient's condition make the patient unsuitable for further treatment, or if after 4
cycles the patient is not deriving clinical benefit from the treatment in the judgment of
the investigator. After 12 months, responding patients may continue on oral lenalidomide
alone daily (at the dose tolerated by the patient) for 21 days of a 28 day cycle until
disease progression, toxicity or death.
Response to treatment and disease progression will be assessed by collecting and evaluating
bone marrow aspirates within 10 days of the first dose of cycles 3 and 5 and every three
cycles thereafter (every 12 weeks) until confirmation of a complete response. Once
confirmed 1 month later, patients will not undergo bone marrow assessments until there is
evidence of progression.
Blood tests will include weekly CBC with differential and platelet count, electrolytes, BUN
and creatinine for the first 8 weeks, then every 2 weeks until on stable doses, then every 4
weeks thereafter or as clinically indicated. Liver profile will be measured monthly. Bone
marrow biopsies/aspirates will be centrally reviewed during or at the end of the study.
Approximately 30 days after receiving the last dose of study drug, patients will be
reassessed for toxicity, patient status and relapse/progression if applicable. Thereafter,
patients will be re-assessed every 3 months until death or loss to follow-up.
Biomarkers of angiogenesis will be measured at the following frequencies: CECs and CEPs at
baseline, monthly x 3 then q 3 monthly x 2 then at time of progression or coming off
study.Marrow and peripheral blood soluble VEGF and VEGFR-1 and 2 will be measured by ELISA
at the same frequency as the bone marrows.Cytogenetics will be performed at baseline, at 3
months and at completion of the study.
STUDY DURATION: 12 months for lenalidomide + melphalan; option to remain on lenalidomide
alone if ongoing response at 12 months TOTAL SAMPLE SIZE: 20
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Overall Response Rate (RR) (as defined by modified international working group standardized response criteria)
Rena J Buckstein, MD FRCPC
Odette Cancer Center
Canada: Canadian Institutes of Health Research