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

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

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 Overview

• Status: Terminated
• Conditions: Multiple Myeloma
• Intervention / Treatment: Drug: Lenalidomide

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.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 1

Contacts and Locations

Study Locations

• France
  • Pessac, France, 33600
    • CHU Bordeaux - Hôpital Haut-Lévêque

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: lenalidomide

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
One-year Progression-Free Survival	Progression defined according to International Myeloma Working Group (IMWG) criteria	one year
One-year Overall Survival	all-cause death	one year
One-year Transplant Related Mortality		one year
One-year incidence of Relapse/Progression	Progression defined according to IMWG criteria	one year
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
Immunophenotypic analysis of blood B, T, NK and dendritic cells		one year
Chimerism analysis		one year
safety of lenalidomide	all adverse events, graded according to NCI-CTCAE v3	one year

Collaborators and Investigators

• Sponsor: University Hospital, Bordeaux
• Investigators: Principal Investigator: Stephane Vigouroux, Dr, University Hospital, Bordeaux; Study Chair: Adélaïde DOUSSAU, Dr, University Hospital, Bordeaux

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: August 22, 2011
• First Submitted That Met QC Criteria: August 22, 2011
• First Posted (Estimated): August 23, 2011

Study Record Updates

• Last Update Posted (Actual): May 22, 2026
• Last Update Submitted That Met QC Criteria: May 20, 2026
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: lenalidomide
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Neoplasms; Immune System Diseases; Neoplasms by Histologic Type; Hematologic Diseases; Lymphoproliferative Disorders; Immunoproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders; Hemic and Lymphatic Diseases; Multiple Myeloma; Organic Chemicals; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Carboxylic Acids; Piperidines; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Piperidones; Isoindoles; Lenalidomide
• Other Study ID Numbers: CHUBX 2010/01; 2010-023203-98 (EudraCT Number)