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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01421927
First received: August 22, 2011
Last updated: August 6, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Multiple Myeloma
Drug: Lenalidomide
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety of a Maintenance Therapy With Lenalidomide After Reduced-intensity Allogeneic Stem Cell Transplantation for Chemosensitive Relapsed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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


Estimated Enrollment: 13
Study Start Date: August 2011
Estimated Study Completion Date: August 2015
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01421927

Locations
France
CHU Bordeaux - Hôpital Haut-Lévêque
Pessac, France, 33600
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Principal Investigator: Stephane Vigouroux, Dr University Hospital, Bordeaux
Study Chair: Adélaïde DOUSSAU, Dr University Hospital, Bordeaux
  More Information

No publications provided

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01421927     History of Changes
Other Study ID Numbers: CHUBX 2010/01
Study First Received: August 22, 2011
Last Updated: August 6, 2014
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
lenalidomide

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 16, 2014