Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Relapsed Multiple Myeloma (REVALLO)

University Hospital of Bordeaux

Status and phase

Completed

Phase 1

Conditions

Multiple Myeloma

Treatments

Drug: Lenalidomide

Study type

Interventional

Funder types

Other

Identifiers

NCT01421927

CHUBX 2010/01

Details and patient eligibility

About

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.

Full description

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.

Enrollment

13 patients

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Patients aged 18 to 65 years
Multiple Myeloma in 2nd or 3rd complete or partial response*
Disease never refractory to lenalidomide
Lenalidomide treatment ≤ 9 months
HLA related or unrelated donor (matched 10/10 or mismatched 9/10 HLA-C high resolution level or HLA-DQ high or low resolution level)
Insured under Social Security
Information and consent signed

Exclusion criteria

Stable or progressive disease
Hypersensitivity to lenalidomide or excipients
Lenalidomide treatment > 9 months
Absence of efficient contraception in women or men
Cardiac insufficiency (ejection fraction < 50% by echocardiography)
Pulmonary disease characterized by DLCO < 60%
Severe renal insufficiency (clearance of creatinin < 30 ml/min)
Hepatic disease characterized by ASAT and/or ALAT and/or total bilirubin > 2 times the upper normal value except in case of Gilbert's disease
Bacterial, Viral or Fungal uncontrolled infections
No contraceptive method for Female subjects of childbearing potential
No use of condoms for males subjects
Pregnant or breast feeding woman
History of previous cancer (other than myeloma) except if the patient is in complete remission for more than 5 years.