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

Phase 1

Completed

• Conditions: Multiple Myeloma
• Interventions: Drug: Lenalidomide

• Registration Number: NCT01421927
• Lead Sponsor: University Hospital, Bordeaux

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.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2011-08
• Study First Submitted: 2011-08-22
• Study First Submitted QC: 2011-08-22
• Study First Posted: 2011-08-23
• Primary Completion: 2014-10
• Study Completion: 2014-10
• Status Verified: 2015-07
• Last Update Submitted: 2015-07-22
• Last Update Posted: 2015-07-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 13

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

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
lenalidomide	Lenalidomide	-

Primary Outcome Measures

Name	Time	Method
Safety of lenalidomide	1 year	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

Secondary Outcome Measures

Name	Time	Method
One-year Overall Survival	one year	all-cause death
Incidences of acute and chronic Graft versus Host Disease	one year	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	one year
One-year incidence of Relapse/Progression	one year	Progression defined according to IMWG criteria
One-year Progression-Free Survival	one year	Progression defined according to International Myeloma Working Group (IMWG) criteria
One-year Transplant Related Mortality	one year
Chimerism analysis	one year
safety of lenalidomide	one year	all adverse events, graded according to NCI-CTCAE v3

Trial Locations

Locations (1)

CHU Bordeaux - Hôpital Haut-Lévêque; 🇫🇷 Pessac, France