Rationale and design of the German-speaking myeloma multicenter group (GMMG) trial HD6: a randomized phase III trial on the effect of elotuzumab in VRD induction/consolidation and lenalidomide maintenance in patients with newly diagnosed myeloma

• Published in: BMC cancer Vol. 19; no. 1; p. 504
• Main Authors: Salwender, Hans, Bertsch, Uta, Weisel, Katja, Duerig, Jan, Kunz, Christina, Benner, Axel, Blau, Igor W, Raab, Marc Steffen, Hillengass, Jens, Hose, Dirk, Huhn, Stefanie, Hundemer, Michael, Andrulis, Mindaugas, Jauch, Anna, Seidel-Glaetzer, Andrea, Lindemann, Hans-Walter, Hensel, Manfred, Fronhoffs, Stefan, Martens, Uwe, Hansen, Timon, Wattad, Mohammed, Graeven, Ullrich, Munder, Markus, Fenk, Roland, Haenel, Mathias, Scheid, Christof, Goldschmidt, Hartmut
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 28.05.2019; BioMed Central; BMC
• Subjects: Autografts; autologous stem cell transplant; Bortezomib; Care and treatment; Chemotherapy; Clinical trials; Complications and side effects; Dexamethasone; Dosage and administration; Drug dosages; Drug therapy; elotuzumab; Gene expression; Glucocorticoids; Hematopoietic stem cells; high-dose chemotherapy; Immunosuppressive agents; Immunotherapy; Induction therapy; Lenalidomide; Malignancy; Medical imaging; Melphalan; Monoclonal antibodies; Multiple myeloma; Objectives; Patients; Peripheral blood; Quality of life; Stem cell transplantation; Stem cells; Steroids (Organic compounds); Studies; Study Protocol; Surgery; Targeted cancer therapy; Tomography; Toxicity; Transplants & implants; Working groups; Germany; United States > US; elotuzumab; autologous stem cell transplant; Multiple myeloma; high-dose chemotherapy
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-019-5600-x

Despite major advances in therapy, multiple myeloma is still an incurable malignancy in the majority of patients. To increase survival, deeper remissions (i.e. CR) translating into longer PFS need to be achieved. Incorporation of new drugs (i.e. bortezomib and lenalidomide) as induction and maintenance treatment in an intensified treatment concept, including high dose melphalan (200 mg/m ), has resulted in increased CR rates, and is considered the standard of care for younger patients. Elotuzumab in combination with lenalidomide and dexamethasone has given better results as lenalidomide and dexamethasone alone in a phase III trial. The GMMG-HD6 trial will be the first phase III trial investigating the role of elotuzumab in combination with bortezomib, lenalidomide and dexamethasone (VRD) induction/consolidation and lenalidomide maintenance within a high dose concept. GMMG-HD6 is a randomized, open, multicenter phase III trial. The planned recruitment number is 564 NDMM patients. All patients will receive 4 VRD cycles as induction and undergo peripheral blood stem cell mobilization and harvesting. Thereafter they will be treated with high dose melphalan therapy plus autologous stem cell transplantation followed by 2 cycles of VRD consolidation and lenalidomide maintenance. Patients in arm B1 + B2 will additionally receive elotuzumab in the induction phase, whereas patients in A2 + B2 will be treated with elotuzumab added to consolidation and maintenance. The primary endpoint of the trial is PFS. Secondary objectives and endpoints are OS, CR rates after induction therapy comparing the two arms VRD (A1 + A2) vs VRD + elotuzumab (B1 + B2), CR rates after consolidation treatment, best response to treatment during the study, time to progression (TTP), duration of response (DOR), toxicity and quality of life. Since this is the publication of a study protocol of an ongoing study, no results can be presented. This phase III trial is designed to evaluate whether the addition of elotuzumab to an intensified treatment concept with high dose melphalan chemotherapy plus autologous stem cell transplantation and induction, consolidation and maintenance treatment with bortezomib and lenalidomide is able to improve PFS compared to the same concept without elotuzumab. NCT02495922 on June 24th, 2015.