Refractory Primary-cutaneous Large B-cell Lymphoma (Leg-type) Clinical Trial
Official title:
A Multicentre Prospective Phase II Single Arm Trial Evaluating the Benefit of Therapy With Lenalidomide (Revlimid®) in Relapsed or Refractory Primary-cutaneous Large B-cell Lymphoma (Leg-type) After First Line Treatment by Chemotherapy Plus Rituximab for the French Study Group of Cutaneous Lymphoma (GFELC)
In spite of high initial response rate after a first line treatment by R-polychemotherapy,
cutaneous but also extra-cutaneous recurrences occur after 2 years in about half of the
patients with PCBCL-LT. Thereafter there is no consensus concerning patients care:
radiotherapy has only a palliative effect, advanced age often limits using more aggressive
chemotherapies and no treatment has demonstrated a prolonged efficacy in these relapsing
cases. Therefore new alternatives therapeutic options are needed. Lenalidomide has an
antineoplastic pro-apoptotic effect but also immunomodulatory, and antiangiogenic
properties. Preliminary results suggest its efficacy in relapsing or refractory diffuse
large B-cells lymphomas, especially of nongerminal cells phenotype. By analogy with these
results, lenalidomide appears as an attractive candidate in PCLBCL-LT, more specially as it
has a manageable toxicity even in advanced age patients.
If the lenalidomide efficacy is confirmed in relapsing PCLBCL-LT, this will plead its
evaluation as maintenance therapy after R-chemotherapy in order to avoid recurrences.
To assess benefit and safety of lenalidomide in patients with refractory or relapsing
primary cutaneous large B-cell lymphoma leg type (PCBCL-LT) after a first line treatment by
Rituximab and polychemotherapy. The primary endpoint is overall response rate (complete
response and partial response) at 6 months. Response will be assessed according to clinical
and isotopic criteria.
Optional biological study:
A biological collection (skin and blood samples) will be established. Predictive biological
markers of response or of aggressiveness and resistance to the treatment will be
investigated on the skin biopsies by phenotypic and genetic analyses. The recent discovery
of BLIMP1 inactivation or deletion at 6q21 in activated B-cell like type of diffuse large
B-cell systemic lymphoma points to the need of both a global genetic analysis by Array-CGH
with Single Nucleotide Polymorphism study and a specific investigations of the status of
genes such as CDKN2A, BCL2, BCL6 and BLIMP1 by FISH analysis and/or gene dosage. Xenograft
will be performed from skin biopsies in order to develop animal models for PCLBCL-LT.
Lenalidomide stimulates NK cells immunity and enhances anti-tumor responses. It also seems
to modify the phenotype of NK cells through a decrease of the expression of Killer cell
Immunoglobulin-like Receptors and NKp46. The expression of the NK receptors on blood cells
will be analyzed in order to evidence modifications of the phenotypical and functional
changes under treatment, and to search for a correlation with the clinical response to the
treatment.
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Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment