Efficacy Study of Revlimid® and Low Dose Continuously Administered Melphalan to Treat High Risk MDS (REMMYDYS)
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|ClinicalTrials.gov Identifier: NCT00744536|
Recruitment Status : Completed
First Posted : September 1, 2008
Last Update Posted : June 9, 2017
|Condition or disease||Intervention/treatment||Phase|
|Myelodysplastic Syndromes Leukemia, Myelomonocytic, Chronic Angiogenesis||Drug: Lenalidomide and melphalan||Phase 2|
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1. Determine the overall response rates of low dose melphalan used in combination with lenalidomide in higher risk MDS
- Determine the frequency of hematologic improvement of low dose melphalan used in combination with lenalidomide in higher risk MDS·
- Determine the safety and tolerability of low dose melphalan used in combination with lenalidomide in higher risk MDS·
- Determine the effects of low dose melphalan used in combination with lenalidomide on biomarkers of angiogenesis in higher risk MDS·
- 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
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Revlimid®, and Metronomic Melphalan in the Management of Higher Risk Myelodysplastic Syndromes (MDS) and CMML: A Phase 2 Study"|
|Study Start Date :||January 2008|
|Actual Primary Completion Date :||January 2012|
|Actual Study Completion Date :||December 2012|
Experimental: Lenalidomide and Melphalan
Lenalidomide + Melphalan both given metronomically
Drug: Lenalidomide and melphalan
Lenalidomide (Revlimid) 10 mg po daily for 21d/28 Melphalan (Melphalan) 2 mg po daily for 21d/28
- Overall Response Rate (RR) (as defined by modified international working group standardized response criteria) [ Time Frame: 3 years ]Overall Response Rate (RR) (as defined by modified international working group standardized response criteria).
- Percent with hematologic improvement [ Time Frame: 3 years ]Percent with hematologic improvement.
- Percent with cytogenetic remission [ Time Frame: 3 years ]Percent with cytogenetic remission.
- Overall, progression-free and leukemia-free-survival [ Time Frame: 3 yrs ]Overall, progression-free and leukemia-free-survival.
- Percent reduction in baseline biomarkers of angiogenesis including: circulating endothelial cells (CEC) and precursors (CEP), plasma and marrow VEGF and VEGFR 1-2 levels [ Time Frame: 3 yrs ]Percent reduction in baseline biomarkers of angiogenesis including: circulating endothelial cells (CEC) and precursors (CEP), plasma and marrow VEGF and VEGFR 1-2 levels.
- Safety (type, frequency, severity, and relationship of adverse events to study therapy) [ Time Frame: 3 yrs ]Safety (type, frequency, severity, and relationship of adverse events to study therapy).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00744536
|Sunnybrook Health Sciences Centre, Odette Cancer Center|
|Toronto, Ontario, Canada, M4N3M5|
|Principal Investigator:||Rena J Buckstein, MD FRCPC||Odette Cancer Center|