Patients with mantle cell lymphoma are refractory to their regimen or have relapsed once or up to three times. MedDRA version: 20.0 Level: PT Classification code 10061275 Term: Mantle cell lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: Revlimid, 5mg hard capsules
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LENALIDOMIDE
CAS Number: 191732-72-6
Cur
Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Patients with histologically proven mantle cell non-Hodgkin's lymphoma [MCL] {including overexpression of cyclin D1 by immunohistochemistry}. In patients whose tumors are negative for the cyclin D1 overexpression or translocation, evidence of overexpression of cyclin D2 or D3 by immunohistochemistry will be acceptable. • Patients who are refractory to their regimen or have relapsed once, twice or three times and who have documented progressive disease (Refractory to prior chemotherapy regimens is defined as not having reached a CR or PR to prior treatment) • Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2 • Must be >18 years of age at the time of signing the informed consent form. • Must have had at least one prior combination chemotherapy regimen with an alkylating agent, and comprising either an anthracycline and/or cytarabine and/or fludarabine (with or without rituximab) • Prior stem cell transplant is allowed. • Must be ineligible for intensive chemotherapy and/or transplant at time of inclusion in the study • Must have measurable disease on cross sectional imaging by CT (or MRI, if CT is contraindicated) that is at least 2 cm in the longest diameter and measurable in two perpendicular dimensions • Must be able to adhere to the study visit schedule and other protocol requirements • Life expectancy of greater than 3 months • Females of childbearing potential (FCBP) must: - Have two negative medically supervised pregnancy tests prior to starting of study therapy. She must agree to ongoing pregnancy testing during the course of the study, and after end of study therapy. This applies even if the patient practices complete and continued sexual abstinence - Either commit to continued abstinence from heterosexual intercourse (which must be reviewed on a monthly basis) or agree to use, and be able to comply with, effective contraception without interruption, 28 days prior to starting study drug, during the study therapy (including dose interruptions), and for 28 days after discontinuation of study therapy • Male patients must: - Agree to use a condom during sexual contact with a FCBP, even if they have had a vasectomy, throughout study drug therapy, during any dose interruption and after cessation of study therapy - Agree to not donate semen or sperm during study drug therapy and for 28 days after end of study drug therapy • All patients must: - Have an understanding that the study drug could have a potential teratogenic risk. - Agree to abstain from donating blood while taking study drug therapy and for 28 days after end of study drug therapy - Agree not to share study medication with another person. - Agree to be counseled about pregnancy precautions and risks of fetal exposure. Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 75 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 175
Exclusion criteria
Exclusion criteria: • Diagnosis of lymphoma other than mantle cell lymphoma • Prior history of malignancies, other than mantle cell lymphoma, unless the patient has been free of the disease for = 5 years. Exceptions include the following: - Basal cell carcinoma of the skin - Squamous cell carcinoma of the skin - Carcinoma in situ of the cervix - Carcinoma in situ of the breast - Incidental histological finding of prostate cancer (TNM stage of T1a or T1b) • Transformed lymphoma • Prior use of lenalidomide • Patients who are candidates for autologous or allogeneic transplantation at the time of inclusion in the study • Prior allogeneic transplantation with persistent donor hematopoiesis • Prior radiotherapy within 4 weeks prior to randomization • Active CNS lymphoma with the exception of those patients whose CNS lymphoma has been treated with chemotherapy, radiotherapy or surgery, have remained asymptomatic for 90 days (3 months) and demonstrate no CNS lymphoma as shown by lumbar puncture, CT/brain MRI are eligible. Patients with a history of CNS involvement or CNS symptoms will be required to have negative CSF cytology examination and a head CT during the screening period (known and active CNS or leptomeningeal involvement). • Known seropositive for or active viral infection with human immunodeficiency virus (HIV) • Known seropositive for or active viral infection with hepatitis B virus: - HBsAg positive. - HBsAg negative, anti-HBs positive and/or anti-HBc positive and detectable viral DNA. - Patients who are HBsAg negative and viral DNA negative are eligible. - Patients who had hepatitis B but have received an antiviral treatment and show no detectable viral DNA for 6 months are eligible. - Patients who are seropositive because of hepatitis B virus vaccine are eligible. • Known seropositive for or active viral infection with hepatitis C virus - Patients who had hepatitis C but have received an antiviral treatment and show no detectable viral RNA for 6 months are eligible. • Patients who are not willing to take DVT prophylaxis, if they are at risk • Patients should not be receiving corticosteroids 7 days prior to randomization, except for prednisone = 10 mg/day or equivalent for purposes other than treating MCL • Pregnant or lactating females • Any of the additional following laboratory abnormalities: - Absolute neutrophil count (ANC) 3.0 x upper limit of normal (ULN), except in patients with documented liver involvement by lymphoma - Serum total bilirubin > 1.5 x ULN, except in case of Gilbert’s Syndrome and documented liver involvement by lymphoma. - Calculated creatinine clearance (Cockcroft-Gault formula) of < 30 mL/min • Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from signing the informed consen
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To compare the progression free survival (PFS) of lenalidomide monotherapy versus investigator’s choice single agent in patients with mantle cell lymphoma (MCL) who are refractory to their regimen or have relapsed once or up to three times.;Primary end point(s): • Progression free survival ; Secondary Objective: • To determine the overall response rate (ORR) of lenalidomide monotherapy or investigator’s choice single agent in patients with relapsed or refractory MCL. • To evaluate the safety of lenalidomide monotherapy or investigator’s choice single agent in patients with relapsed or refractory MCL. • To determine the time to progression, and overall survival of patients with relapsed or refractory MCL who have received treatment with lenalidomide or investigator’s choice single agent. • To investigate the health-related quality of life (QoL) of patients treated with lenalidomide or investigator’s choice single agent treatment. ; Timepoint(s) of evaluation of this end point: • All patients will be followed for progression-free survival and for overall survival after progression every 90 days. • Patients will be followed until death or until either 70% of the patients have died or the median follow-up in responding patients is > 2 years or the median duration of response (overall response and CR/CRu) has been reached, or four years from last patient randomized, whichever comes later • The primary analysis for PFS to be performed on the ITT and FAS populations will be conducted 1 year after the last patient is randomized | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Overall response rate ( [CR], [CRu], [PR]) • Duration of response • Tumor control rate (Rates for CR, CRu, PR, and stable disease [SD]) • Time to progression • Time to treatment failure • Time to tumor response • Overall survival (OS) • Quality of Life (EORTC QLQ-C30) • Safety ; Timepoint(s) of evaluation of this end point: • Secondary endpoints will be analyzed at the time of the primary analysis of response. An update of the time to events endpoints and overall survival will be done at the end of the follow up. • The Follow-Up Phase will continue until either patient death or 70% of the patients have died, or the median follow-up in responding patients is > 2 years, or the median duration of response (overall response and CR/CRu) has been reached, or four years from last patient randomized, whichever comes later. | — |
Countries
Belgium, Czech Republic, Denmark, France, Germany, Greece, Israel, Italy, Russian Federation, Spain, Sweden, United Kingdom
Contacts
Public ContactClinicalTrialDisclosure
Celgene Europe Limited
Outcome results
None listed