A Point Nomme/Just in Time

A Trial of Single Autologous Transplant With or Without Consolidation Therapy Versus Tandem Autologous Transplant With Lenalidomide Maintenance for Patients With Multiple Myeloma (BMT CTN 0702)

NCT01109004

National Heart, Lung, and Blood Institute (NHLBI)

Blood and Marrow Transplant Clinical Trials Network and National Cancer Institute (NCI)

63 study sites throughout the United States

750 patients

This is a phase III, multicenter trial. There are three comparison arms: tandem autologous transplants followed by maintenance therapy; a single autologous transplant followed by consolidation therapy with lenalidomide, bortezomib, and dexamethasone followed by maintenance therapy; and a single autologous transplant followed by maintenance therapy. Eligible patients are those with symptomatic myeloma, age 70 years or younger, and have a Karnofsky performance score of ≥ 70 percent who have received at least two cycles of any regimen as initial systemic therapy and are within two to 12 months of the first dose of initial therapy. Comparisons will be made between the two single transplant arms and between each single transplant arm and the tandem transplant arm. The primary outcome measure is three-year progression-free survival. Secondary endpoints include myeloma-stable survival measured at four years, three-year overall survival, incidence of progression, incidence of toxicities, incidence of infection, treatment related mortality, non-compliance with medications, and quality of life.

The focus of this study is on evaluating the benefit of consolidation in patients with myeloma who undergo high-dose chemotherapy with melphalan followed by stem cell rescue. The following two types of consolidation are included in the study: a second round of high-dose chemotherapy with melphalan followed by autologous stem cell rescue (ASCR) (i.e., tandem transplant) and the myeloma active regimen of lenalidomide, dexamethasone, and bortezomib (i.e., RVD) (lenalidomide 15 mg/day on days 1-14; dexamethasone 40 mg on days 1, 8, and 15; and bortezomib 1.3 mg/m2 on days 1, 4, 8, and 11 of every 21 day cycle; patients will receive four cycles). Patients on the third arm of the study receive no consolidation. Patients on all three arms receive maintenance therapy with lenalidomide starting at 10 mg daily for three months and subsequently increasing to 15 mg daily for the duration of the study. The study addresses two important questions about management of patients with myeloma who undergo high-dose chemotherapy followed by ASCR: Does consolidation improve outcome? If so, which consolidation strategy is better, tandem transplant or combination therapy with the highly active myeloma regimen RVD?

The use of a second course of high-dose chemotherapy followed by a second autologous transplant (i.e., tandem transplant) as a form of consolidation therapy for treatment of myeloma antedated the development of highly active therapeutic combinations that include immunomodulatory drugs such as lenalidomide and proteasome inhibitors such bortezomib in combination with dexamethasone. The current study investigates the efficacy and safety of the RVD regimen when used as consolidation therapy following high-dose melphalan with ASCR and compares the results with the tandem transplant as consolidation. The study will also examine whether consolidation of either type is necessary given the proven efficacy of maintenance therapy following treatment with high-dose chemotherapy followed ASCR (N. Engl. J. Med. 2012; 366:1770-1781 and N. Engl. J. Med. 2012; 366:1782-1791). Importantly, in ongoing trials, IFM/DFCI 2009 (NCT01191060) and DFCI 10-106 (NCT01208662), the efficacy and safety of high-dose chemotherapy followed by ASCR is being compared directly with the RVD regimen as initial therapy for patients with myeloma 65 years old or younger. The results of this study when combined with the results of the current study should provide clinicians with a consensus, evidence-based approach to treatment of myeloma in transplant eligible patients, a point nommé.