Overview

Pom-dex Versus Pom-Cyclo-dex in MM Patients With Biochemical or Clinical Relapse, During Lena Maintenance Treatment

Status:
Terminated
Trial end date:
2019-12-31
Target enrollment:
Participant gender:
Summary
The combination lenalidomide plus low-dose dexamethasone (Rd) is an active treatment for Multiple Myeloma (MM) patients, both at diagnosis and at relapse. Pomalidomide, is an immunomodulatory molecule (IMID), derivative of thalidomide, developed to improve the efficacy and reduce the toxicity of the parent molecule. Pomalidomide and dexamethasone (pom-dex) proved to be an effective and safe treatment in MM patients refractory to lenalidomide and refractory/intolerant to bortezomib. The addition of chemotherapy to novel drugs has been evaluated both at diagnosis and at relapse. The combination of pomalidomide-cyclophosphamide-prednisone proved to be safe and effective in relapsed/refractory MM patients. The combination pomalidomide-cyclophosphamide-dexamethasone (pom-cyclo-dex) was tested in a phase II study in patients with relapsed and refractory MM, demonstrating a good tolerability using pomalidomide at the dose of 4 mg. Pom-cyclo-dex resulted in a superior response rate and Progression-Free Survival (PFS) compared to pom-dex. The increased hematologic toxicities, as a result of the addition of oral cyclophosphamide, were manageable. With an overall response rate of 65% the combination demonstrated a promising efficacy.The first aim of our trial, is to compare the combination of pom-cyclo-dex vs pom-dex. Relapsed myeloma is defined as previously treated myeloma that progresses and requires the initiation of salvage therapy. According to International Myeloma Working Group (IMWG) recommendation, biochemical relapse is defined as an increase of ≥ 25% of tumor burden from lowest value, without any CRAB feature (CRAB is defined as the onset of clinical symptoms: hypercalcemia, renal failure, anemia and bone lesions) and detected in 2 consecutive determinations. Clinical relapse requires one or more direct indicators of progressive disease and end organ dysfunction (CRAB features). Treatment at relapse should start in case of clinical relapse or a significant paraprotein increase (doubling of M-component in 2 months). In case of biochemical relapse the standard is observation only, as in case of asymptomatic MM at diagnosis. However, a recently published trial, showed improved PFS and OS for newly diagnosed asymptomatic patients treated with lenalidomide and dexamethasone in comparison with observation only. Our hypothesis is that similarly, in the relapse setting, patients may benefit from an early intervention, meaning a treatment at biochemical relapse and not only in case of clinical relapse or rapid increase of M-component.
Phase:
Phase 3
Details
Lead Sponsor:
Fondazione EMN Italy Onlus
Fondazione Neoplasie Sangue Onlus
Treatments:
BB 1101
Cyclophosphamide
Dexamethasone
Dexamethasone acetate
Pomalidomide
Thalidomide