NCT02928419

Efficacy of Eltrombopag Plus Lenalidomide Combination Therapy in Patients With IPSS Low and Intermediate-risk Myelodysplastic Syndrome With Isolated del5q

Efficacy of Eltrombopag Plus Lenalidomide Combination Therapy in Patients With IPSS Low and Intermediate-risk Myelodysplastic Syndrome With Isolated del5q: a Multicenter, Randomized, Double-blind, Placebo Controlled Study - QOL-ONE Rev2MDS

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 2 (actual)
• Sponsor: Associazione Qol-one · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Myelodysplastic syndromes (MDS) prevail in elderly patients and are characterized by inefficient erythropoiesis and peripheral cytopenias. Supportive care still represents the main therapeutic option in most patients. Quality of life is deteriorated mostly by anemia and by limitations due to dependence on transfusions, thrombocytopenia, and neutropenia. The only treatment available for severe thrombocytopenia consists of PLT transfusions, mainly in the presence of bleeding. In patients with low and intermediate-1 risk MDS with an isolated deletion 5q cytogenetic abnormality, red blood cell (RBC) transfusion-dependence is a prevalent condition. For these latter patients reaching transfusion-dependence, lenalidomide, an immunomodulatory drug, has been approved by FDA and EMA. It has been shown that the drug induces significant erythroid (about 65%) and cytogenetic responses which have been associated with a survival benefit. In patients with MDS with del5q and serum erythropoietin levels \> 500 miU/L, lenalidomide dosing of 10 mg/day for 21 days every 28, rather than 5 mg dosing, induces higher rates of transfusion-independence and cytogenetic responses with a trend to survival advantage. As a consequence, the recommended starting dose of lenalidomide is 10 mg orally once daily on days 1-21 of repeated 28-day cycles. Lenalidomide treatment must not be started if the Absolute Neutrophil Counts (ANC) \< 0.5 Gi/L and/or PLT counts \< 25 Gi/L. For patients who are dosed initially at 10 mg and who experience thrombocytopenia \< 25 Gi/L (45-75%), it is recommended to interrupt lenalidomide treatment until PLT count returns to ≥ 25 Gi/L on at least 2 occasions for ≥ 7 days or when the PLT count recovers to ≥ 50 Gi/L at any time, to resume lenalidomide at 50% dose reduction. Eltrombopag is an orally bioavailable agonist of the thrombopoietin receptor. It has been shown that in patients affected by MDS and by acute myeloid leukemia, Eltrombopag neither increases the proliferation, nor the clonogenic growth capacity of bone marrow blasts. Furthermore, Eltrombopag induces an increase in the megakaryocytic differentiation and in the formation of normal megakaryocytic colonies. These results provide the rationale for pursuing further research on Eltrombopag for the treatment of thrombocytopenia in case of MDS. Preliminary results of an ongoing randomized trial, EQoL-MDS, for the evaluation of efficacy, safety of eltrombopag for thrombocytopenia of low and intermediate-1 IPSS risk MDS has shown that eltrombopag is able to significantly raise PLT counts in about 65% of patients without additional toxicity Furthermore, the combination of lenalidomide and eltrombopag resulted in significant inhibitory effects on the growth of leukemic colonies in the majority of primary MDS and AML samples. Most importantly, eltrombopag was able to reverse the anti-megakaryopoietic effects of lenalidomide in primary MDS patient samples. These results provide a preclinical rationale for the use of this combination in MDS and AML

Conditions

• Myelodysplastic Syndromes

Interventions

Type	Name	Description
DRUG	Eltrombopag/Revolade	From day 1, patients presenting with PLT counts ≤ 100 Gi/L at any time will receive oral eltrombopag for a maximum of 36 months. Starting dose will depend on PLT count determined on the day of first dose of eltrombopag. For patients experiencing PLT count 70 to 100 Gi/L, initial dosing is 50 mg/day. For subjects presenting with PLT counts \< 70 Gi/L initial dosing is 100 mg/day. The dose of study medication must be increased sequentially by 50 mg every 7 days, up to a maximum dose of 300 mg/day until PLT ≥ 100 Gi/L. For East Asian subjects, a maximum dose of 150 mg is permitted.
OTHER	Placebo	From day 1, patients presenting with PLT counts ≤ 100 Gi/L at any time will receive oral placebo for a maximum of 36 months. Starting dose will depend on PLT count determined on the day of first dose of placebo. For patients experiencing PLT count 70 to 100 Gi/L, initial dosing is 50 mg/day. For subjects presenting with PLT counts \< 70 Gi/L initial dosing is 100 mg/day. The dose of study medication must be increased sequentially by 50 mg every 7 days, up to a maximum dose of 300 mg/day until PLT ≥ 100 Gi/L. For East Asian subjects, a maximum dose of 150 mg is permitted.
DRUG	Lenalidomide	All patients will receive oral lenalidomide 10 mg/day for 21 days every 28 days. Patients will receive lenalidomide dosing according to the lenalidomide product information. Patients obtaining an erythroid response according to IWG 2006 criteria within the first 24 weeks will continue lenalidomide treatment until progression or other reasons for permanent discontinuation

Timeline

• Start date: 2015-05-01
• Primary completion: 2018-09-01
• Completion: 2018-09-01
• First posted: 2016-10-10
• Last updated: 2018-09-25

Locations

50 sites across 3 countries: France, Greece, Italy