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

This study is currently recruiting participants.
Verified January 2014 by University Hospital, Bordeaux
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01421927
First received: August 22, 2011
Last updated: January 31, 2014
Last verified: January 2014

August 22, 2011
January 31, 2014
August 2011
August 2014   (final data collection date for primary outcome measure)
Safety of lenalidomide [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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
Safety of lenalidomide [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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 CTCAE v3.0 occurring at the lowest dose of lenalidomide or
  • Steroid-refractory acute (Seattle criteria) or chronic (NIH criteria) graft versus host disease or
  • Transplant-related death
Complete list of historical versions of study NCT01421927 on ClinicalTrials.gov Archive Site
  • One-year Progression-Free Survival [ Time Frame: one year ] [ Designated as safety issue: No ]
    Progression defined according to International Myeloma Working Group (IMWG) criteria
  • One-year Overall Survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    all-cause death
  • One-year Transplant Related Mortality [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • One-year incidence of Relapse/Progression [ Time Frame: one year ] [ Designated as safety issue: No ]
    Progression defined according to IMWG criteria
  • Incidences of acute and chronic Graft versus Host Disease [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Chimerism analysis [ Time Frame: one year ] [ Designated as safety issue: No ]
  • safety of lenalidomide [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    all adverse events, graded according to NCI-CTCAE v3
  • One-year Progression-Free Survival [ Time Frame: one year ] [ Designated as safety issue: No ]
    Progression defined according to IMWG criteria
  • One-year Overall Survival [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    all-cause death
  • One-year Transplant Related Mortality [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • One-year incidence of Relapse/Progression [ Time Frame: one year ] [ Designated as safety issue: No ]
    Progression defined according to IMWG criteria
  • Incidences of acute and chronic Graft versus Host Disease [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: one year ] [ Designated as safety issue: Yes ]
  • Chimerism analysis [ Time Frame: one year ] [ Designated as safety issue: No ]
  • safety of lenalidomide [ Time Frame: one year ] [ Designated as safety issue: Yes ]
    all adverse events, graded according to NCI-CTCAE v3
Not Provided
Not Provided
 
Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Relapsed Multiple Myeloma
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.

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.

Interventional
Phase 1
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Multiple Myeloma
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
Experimental: lenalidomide
Intervention: Drug: Lenalidomide
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
13
August 2015
August 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years to 65 Years
No
Contact: Stephane Vigouroux, Dr stephane.vigouroux@chu-bordeaux.fr
France
 
NCT01421927
CHUBX 2010/01
Yes
University Hospital, Bordeaux
University Hospital, Bordeaux
Not Provided
Principal Investigator: Stephane Vigouroux, Dr University Hospital, Bordeaux
Study Chair: Adélaïde DOUSSAU, Dr University Hospital, Bordeaux
University Hospital, Bordeaux
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP