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

Multiple Myeloma Clinical Trial

— REVALLO  

Official title:

Safety of a Maintenance Therapy With Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Chemosensitive Relapsed Multiple Myeloma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01421927
• Other study ID #: CHUBX 2010/01
• Status: Completed
• Phase: Phase 1
• First received: August 22, 2011
• Last updated: July 22, 2015
• Start date: August 2011
• Est. completion date: October 2014

Study information

• Verified date: July 2015
• Source: University Hospital, Bordeaux
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 13
• Est. completion date: October 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell

Intervention

Drug:
• Lenalidomide
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. - Duration until persistent stringent complete response for 3 months or progression defined by IMWG criteria12 or unacceptable toxicity or one year after transplant

Locations

Country	Name	City	State
France	CHU Bordeaux - Hôpital Haut-Lévêque	Pessac

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Bordeaux

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety of lenalidomide	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	1 year	Yes
Secondary	One-year Progression-Free Survival	Progression defined according to International Myeloma Working Group (IMWG) criteria	one year	No
Secondary	One-year Overall Survival	all-cause death	one year	Yes
Secondary	One-year Transplant Related Mortality		one year	Yes
Secondary	One-year incidence of Relapse/Progression	Progression defined according to IMWG criteria	one year	No
Secondary	Incidences of acute and chronic Graft versus Host Disease	Acute graft versus host disease according to Seattle criteria. Chronic graft versus host disease according to NIH criteria.	one year	Yes
Secondary	Immunophenotypic analysis of blood B, T, NK and dendritic cells		one year	Yes
Secondary	Chimerism analysis		one year	No
Secondary	safety of lenalidomide	all adverse events, graded according to NCI-CTCAE v3	one year	Yes