Lenalidomide in Relapsed or Refractory Primary-cutaneous Large B-cell Lymphoma Leg-type : Multicentre Prospective Phase II Single Arm Trial of the French Study Group of Cutaneous Lymphoma (REV-LEG)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Bordeaux
ClinicalTrials.gov Identifier:
NCT01556035
First received: March 12, 2012
Last updated: October 28, 2015
Last verified: October 2015
  Purpose

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.


Condition Intervention Phase
Refractory Primary-cutaneous Large B-cell Lymphoma (Leg-type)
Drug: Lenalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by University Hospital, Bordeaux:

Primary Outcome Measures:
  • Overall response rate (complete response CR and partial response PR) at 6 months [ Time Frame: 6 months after study treatment start ] [ Designated as safety issue: Yes ]
    Response will be assessed according to clinical and isotopic criteria.


Secondary Outcome Measures:
  • Overall response rate (complete response CR and partial response PR) at 12 months [ Time Frame: 12 months after study treatment start ] [ Designated as safety issue: Yes ]
    Response will be assessed according to clinical and isotopic criteria.

  • Duration of response [ Time Frame: Every 6 months ] [ Designated as safety issue: Yes ]
    Time between the first PR and progression

  • Progression-free survival [ Time Frame: Every 6 months ] [ Designated as safety issue: Yes ]
    Time between the beginning of the treatment by lenalidomide and progression or death

  • Overall survival and disease specific survival [ Time Frame: Evrey 6 months ] [ Designated as safety issue: Yes ]
  • Safety : description of adverse events occured including grade based on CTCAE v4.0 [ Time Frame: Monthly during treatment duration (up to 12 months) ] [ Designated as safety issue: Yes ]
  • Quality of life [ Time Frame: Every 2 months during treatment duration (up to 12 month) ] [ Designated as safety issue: No ]

Enrollment: 19
Study Start Date: July 2012
Study Completion Date: August 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Lenalidomide treatment Drug: Lenalidomide
Patient orally treated with lenalidomide 25 mg daily for 21 days with 7 days rest of a 28 days cycle.Treatment maintained for 12 months unless progression

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Biopsy-proven Primary cutaneous large B-cell lymphoma leg-type
  • Clinically measurable skin involvement (T1-T3) or skin and nodal (N1-N3) involvement measurable by PET-CT, corresponding to :

Relapse after initial complete response (CR) after R-polychemotherapy Or Partial response or stable disease after R-polychemotherapy

  • Age > 18 years
  • Life expectancy > 3 months
  • WHO performance status 0-2
  • Skin biopsy performed at the inclusion on a skin tumor : new tumor in case of relapsing PCLBCL-LT or initial skin tumor refractory to the previous treatment
  • Signed informed consent for clinical and biological analyses. The Lenalidomide Information Sheet will be given to each patient receiving lenalidomide study therapy. The patient must read this document prior to starting lenalidomide study treatment and each time they receive a new supply of study drug.
  • Social security cover
  • Conditions of global RPP have to be fulfilled by all the patients
  • The Lenalidomide Education and Counseling Guidance Document must be completed and signed by either a trained counselor or the Investigator at the participating clinical center prior to each dispensing of lenalidomide study treatment. A copy of this document must be maintained in the patient records.

Exclusion Criteria:

  • Central nervous system involvement (cerebral CT scan is performed at the inclusion)
  • One or more of the biological abnormalities :

Neutrophil count < 1,500/mm3 ; Platelet count < 60,000/mm3 ; Transaminases > 5 x upper limit of normal ; Total bilirubin > 2.0 mg/dl (34 µmol/L)/ conjugated bilirubin>0.8 mg/dL, except of haemolytic anemia ; Creatinine clearance < 50 mL /min ( measured or calculated according to the method of Cockcroft-Gault)

  • Pregnant or lactating females, potentially childbearing females defined by sexually mature female who: 1) has not undergone a hysterectomy (the surgical removal of the uterus) or bilateral oophorectomy (the surgical removal of both ovaries) or 2) has not been naturally postmenopausal (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time during the preceding 24 consecutive months.
  • Patients should not receive steroids continuously except for prednisone for tumoral flare treatment
  • Uncontrolled infectious and thromboembolic diseases
  • Subjects not willing to take deep venous thrombosis prophylaxis
  • Prior history of malignancies unless the subject has been free of the disease for ≥5 years. Exceptions include basal cell skin carcinoma, carcinoma in situ of the cervix or of the breast
  • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form
  • Known seropositive for or active viral infection with HIV, Hepatitis B and C virus.
  • Uncontrolled intercurrent illness including, but not limited to ongoing or active infection requiring parenteral antibiotics, uncontrolled diabetes mellitus as defined by the investigator
  • Chronic symptomatic congestive heart failure (III or IV of the NYHA Classification for Heart Disease)
  • Unstable angina pectoris, angioplasty or myocardial infarctions within 6 months
  • Clinically significant cardiac arrhythmia that is symptomatic or requires treatment, or asymptomatic sustained ventricular tachycardia.
  • Prior ≥ Grade 3 allergic reaction/hypersensitivity or desquamative rash while taking thalidomide
  • Any standard or experimental anti-cancer drug therapy or radiation within 3 weeks of the initiation of study drug therapy.
  • Participation in another clinical trial
  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: NCT01556035

Locations
France
CHU Amiens, Hôpital Sud
Amiens, France, 80054
CHU Besançon, Hôpital Saint-Jacques
Besançon, France, 25030
AP-HP Hôpital Avicenne
Bobigny, France, 93009
AP-HP Hôpital Ambroise Paré
Boulogne-billancourt, France, 92104
CHU de Clermont-Ferrand, Estaing
Clermont-ferrand, France, 63003
AP-HP Hôpital Henri Mondor
Creteil, France, 94010
CHU de Dijon, Le Bocage
Dijon, France, 21079
CHU de Grenoble
Grenoble, France, 38043
CHU de Lille Hôpital Claude Huriez
Lille, France, 59037
Centre Léon Bérard
Lyon, France, 69373
AP-HM Hôpital Nord
Marseille, France, 13915
CHRU de Montpellier Hôpital Saint-Eloi
Montpellier, France, 34295
CHU de Nantes, Hôtel Dieu
Nantes, France, 44093
CHU de Nice Groupe hospitalier l'Archet
Nice, France, 06202
AP-HP Groupe hospitalier Cochin
Paris, France, 75679
AP-HP- Hôpital Saint Louis
Paris, France, 75475
AP-HP Groupe hospitalier Bichat - Claude Bernard
Paris, France, 75877
AP-HP Hôpital Tenon
Paris, France, 75970
CHU de Bordeaux Hôpital du Haut Lévèque
Pessac, France, 33604
CHU Lyon Sud
Pierre Benite, France, 69450
CHU de Reims, Hôpital Robert Debré
Reims, France, 51092
CHU de Rouen, Hôpital Charles Nicolle
Rouen, France, 76031
CHU de Toulouse Hôpital Larrey
Toulouse, France, 31059
CHU de Tours- Hôpital Trousseau
Tours, France, 37044
Sponsors and Collaborators
University Hospital, Bordeaux
Investigators
Study Chair: Adelaïde DOUSSAU, MD University Hospital Bordeaux, USMR
  More Information

Responsible Party: University Hospital, Bordeaux
ClinicalTrials.gov Identifier: NCT01556035     History of Changes
Other Study ID Numbers: CHUBX 2011/28 
Study First Received: March 12, 2012
Last Updated: October 28, 2015
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by University Hospital, Bordeaux:
oncodermatology
hematology
cutaneous B cell lymphoma
lenalidomide

Additional relevant MeSH terms:
Lymphoma
Lymphoma, B-Cell
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Lymphoma, Non-Hodgkin
Lenalidomide
Thalidomide
Immunologic Factors
Physiological Effects of Drugs
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents
Immunosuppressive Agents
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on July 24, 2016