Clinical trial NCT01421927: Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Relapsed Multiple Myeloma
Official title: Safety of a Maintenance Therapy With Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Chemosensitive Relapsed Multiple Myeloma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Myeloma
Keywords: lenalidomide
Lead sponsor: University Hospital, Bordeaux
Sponsor class: OTHER
First posted: 2011-08-23
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Safety of lenalidomide
timeFrame: 1 year
Secondary outcomes:
measure: One-year Progression-Free Survival
timeFrame: one year
measure: One-year Overall Survival
timeFrame: one year
measure: One-year Transplant Related Mortality
timeFrame: one year
measure: One-year incidence of Relapse/Progression
timeFrame: one year
measure: Incidences of acute and chronic Graft versus Host Disease
timeFrame: one year
measure: Immunophenotypic analysis of blood B, T, NK and dendritic cells
timeFrame: one year
measure: Chimerism analysis
timeFrame: one year
measure: safety of lenalidomide
timeFrame: one year
Other outcomes:
Locations:
city: Pessac
country: France
facility: CHU Bordeaux - Hôpital Haut-Lévêque
Study officials:
affiliation: University Hospital, Bordeaux
name: Stephane Vigouroux, Dr
role: PRINCIPAL_INVESTIGATOR
affiliation: University Hospital, Bordeaux
name: Adélaïde DOUSSAU, Dr
role: STUDY_CHAIR
References: