Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Relapsed Multiple Myeloma (REVALLO)
Allogeneic stem cell transplantation (Allo-SCT) in multiple myeloma (MM) remains a controversial topic because of a high risk of relapse and a significant transplant-related mortality (TRM). In an effort to reduce the TRM, most allogeneic transplants in MM are now performed after reduced-intensity conditioning regimens. In these conditions, TRM usually range from 10 to 20%. However, reducing the intensity of the conditioning invariably increases the incidence of relapse to 45 to 60%. As a consequence, post-transplant strategies to reduce the incidence of relapse after reduced-intensity Allo-SCT should be considered and evaluated.
|Study Design:||Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Safety of a Maintenance Therapy With Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Chemosensitive Relapsed Multiple Myeloma|
- Safety of lenalidomide [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
The main judgement criteria will be the occurrence of adverse events (AE) requiring the definitive interruption of lenalidomide :
- Grade 3 or 4 adverse event according to the Common Terminology Criteria for Adverse Events (CTCAE) v3.0 occurring at the lowest dose of lenalidomide or
- Steroid-refractory acute (Seattle criteria) or chronic (National Institutes of Health (NIH) criteria) graft versus host disease or
- Transplant-related death
- One-year Progression-Free Survival [ Time Frame: one year ] [ Designated as safety issue: No ]Progression defined according to International Myeloma Working Group (IMWG) criteria
- One-year Overall Survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]all-cause death
- One-year Transplant Related Mortality [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- One-year incidence of Relapse/Progression [ Time Frame: one year ] [ Designated as safety issue: No ]Progression defined according to IMWG criteria
- Incidences of acute and chronic Graft versus Host Disease [ Time Frame: one year ] [ Designated as safety issue: Yes ]Acute graft versus host disease according to Seattle criteria. Chronic graft versus host disease according to NIH criteria.
- Immunophenotypic analysis of blood B, T, NK and dendritic cells [ Time Frame: one year ] [ Designated as safety issue: Yes ]
- Chimerism analysis [ Time Frame: one year ] [ Designated as safety issue: No ]
- safety of lenalidomide [ Time Frame: one year ] [ Designated as safety issue: Yes ]all adverse events, graded according to NCI-CTCAE v3
|Study Start Date:||August 2011|
|Estimated Study Completion Date:||August 2015|
|Estimated Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Start between Day+100 and Day+120 post-transplant
- Initial dose: 5 mg/day every day
In the absence of thrombocytopenia < 75000/mm3 or neutropenia < 1000/mm3 (with or without G-CSF), increase to the upper level than the ongoing one every third month up to the maximal dose of 15 mg/day every day.
Lenalidomide has a significant clinical activity in patients with relapsed or refractory MM and in patients relapsing after Allo-SCT. The mechanisms of action involve immunomodulation, anti-angiogenesis activity, direct anti tumor activity and effects on microenvironment. So far, the experience with lenalidomide after Allo-SCT has been limited to patients with progressive disease. In such patients, some responses are observed but most of them are transient with median progression-free survivals of less than one year. Lenalidomide used as maintenance therapy in patients with persistent rather than progressive disease might be a better approach.
Lenalidomide is interesting in the Allo-SCT setting also because some recent studies focusing on its immunological properties have suggested that the molecule could stimulate the graft versus myeloma effect. First, it has been demonstrated in vitro that lenalidomide can inhibit the proliferation and the suppressor function of regulatory T cells. Secondly, a clinical study using lenalidomide as salvage therapy after Allo-SCT demonstrated an increase of activated T cells and NK cells. Finally, a case report described a patient's response to lenalidomide associated with the development of an acute graft versus host disease.
Taken together, these data suggest that patients with MM who have a persistent disease after a reduced-intensity Allo-SCT might benefit from a post-transplant maintenance strategy with lenalidomide by a direct anti-tumor effect and a stimulation of the graft versus myeloma effect. The primary objective of this study is to evaluate the safety of such a strategy.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01421927
|Contact: Stephane Vigouroux, Dremail@example.com|
|CHU Bordeaux - Hôpital Haut-Lévêque||Recruiting|
|Pessac, France, 33600|
|Contact: Stephane Vigouroux, Dr firstname.lastname@example.org|
|Principal Investigator: Stephane Vigouroux, Dr|
|Sub-Investigator: Gérald Marit, Pr|
|Sub-Investigator: Noel Milpied, Pr|
|Sub-Investigator: Reza Tabrizi, Dr|
|Sub-Investigator: Krimo Bouabdallah, Dr|
|Sub-Investigator: Anna Schmitt, Dr|
|Sub-Investigator: Thibaut Leguay, Dr|
|Sub-Investigator: Arnaud Pigneux, Dr|
|Sub-Investigator: Marie-Sarah Dilhuydy|
|Principal Investigator:||Stephane Vigouroux, Dr||University Hospital, Bordeaux|
|Study Chair:||Adélaïde DOUSSAU, Dr||University Hospital, Bordeaux|