RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA MedDRA version: 15.1 Level: PT Classification code 10012821 Term: Diffuse large B-cell lymphoma recurrent 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
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Sponsors
Celgene Corporation
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Histologically proven DLBCL following WHO subcategories a.NOS(common morphologic variants,rare morphologic variants,molecular subgroups,and IHC subgroups[CD5+,GCB,non-GCB]) b.Tcell/histiocyte rich c.EBV+of the elderly d.Associated with chronic inflammation e.Submission of an FFPE tumor block or appropriately stained slides from a fresh biopsy is required.If fresh specimen cannot be obtained without putting the patient at unjustifiable risk,then slides prepared from the archival specimen supporting a prior DLBCL diagnosis may be submitted to fulfill this inclusion criterion with medical monitor approval 2.Can wait for subtype results from central pathology prior to randomization.In the event that the patient requires immediate treatment and the sample cannot be submitted to and evaluated by central pathology prior to start of treatment,medical monitor approval for enrollment is required;in this case submission of an appropriate sample(either fresh biopsy acquired prior to Cycle1 Day1 or archival sample) is absolutely required and the sample should be submitted no later than 4 weeks post Cycle1 Day1 3.Relapsed/refractory to a.One combination chemotherapy regimen containing rituximab and an anthracycline or equivalent if anthracycline is contracindicated;and b.At least one additional treatment with either a combination chemotherapy regimen (which must include at least one of:ifosphamide,gemcitabine,etoposide or a platinum agent and rituximad if not previously used)or conditioning regimen containing an alkylating agent followed by autologous or allogenieic SCT.If a patient is documented as ineligible for both the additional combination chemotherapy and SCT at the time of inclusion in the study,they are exempted from requirement 3b c.For patients who have relapsed or progressed after achieving a response(defined as CR or PR),documented,Investigator-assessed relapse or progression after the last treatment is required d.For patients refractory to their last treatment(defined as not having achieved a CR or PR prior to enrollment by Investigatorassessment),documented progression will not be required e.For patients whom the physician considers ineligible for SCT at the time of enrollment because of one or more of the following reasons,documentation of SCT ineligibility is required •Age>65years •Comorbidity for patients<65years(any condition including laboratory abnormalities or clinical symptoms such as e.g. cardiac insufficiency and severe pulmonary diseases that places the patient at an unacceptable risk if he/she undergoes transplant) •Patient declines transplant •Physician considers that patient's disease cannot be adequately treated by autologous transplantation.Possible reasons: active disease following salvage therapy or insufficient CD34 cell collection f.For patients whom the physician considers ineligible for second line combination chemotherapy at the time of enrollment because of one or more of the following reasons,documentation of the ineligibility is required •Poor performance status •Major organ dysfunction or significant medical condition that places the patients at unacceptabl
Exclusion criteria
Exclusion criteria: 1.Diagnosis of lymphoma histologies other than diffuse large B-cell lymphoma. Patients with history of low-grade B-cell NHL;evidence of concurrent,follicular lymphoma;or history of known transformed largecell NHL 2.Prior history of malignancies, other than diffuse large B-cell lymphoma, unless the patient has been free of the disease for=5years.Exceptions to the=5year time limit include history of 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) 3.Prior use of lenalidomide 4.Patients in whom autologous or allogeneic SCT or combination chemotherapy is considered appropriate at the time of inclusion in the study 5.Prior allogeneic SCT with persistent donor hematopoiesis 6.Known seropositive for or history of, active viral infection with human HIV 7. Seropositive for or active viral infection with HBV 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 HBV but have received an antiviral treatment and show no detectable viral DNA for 6 months are eligible •Patients who are seropositive because of HBV vaccination are eligible 8.Known seropositive for or active viral infection with HCV 9.Neuropathy Grade 4 10.The following WHO subcategories of DLBCL a.Active CNS lymphoma with the exception of those patients whose CNS lymphoma has been treated with chemotherapy, radiotherapy or surgery, have remained asymptomatic for 12 weeks(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 cerebrospinal fluid cytology examination and a head CT during the Screening Phase(known and active CNS or leptomeningeal involvement) b.Primary cutaneous,leg type c.Primary mediastinal(thymic) d.Lymphomatoid granulomatosis e.ALK-positive cases f.Plasmablastic lymphoma g.Large B cell lymphoma arising in HHV8 associated multicentric Castleman disease h.Primary effusion lymphoma i.Intravascular large B cell j.Unclassifiable cases with features intermediate between DLBCL and Burkitt k.Unclassifiable cases with features intermediate between DLBCL and classical Hodgkin's lymphoma 11.Patients who are at a high risk for a thromboembolic event and are not willing to take VTE prophylaxis 12.Any of the following laboratory abnormalities a.Absolute neutrophil count<1,500cells/mm3(1.5x10^9/L)unless secondary to bone marrow involvement by lymphoma as demonstrated by recent bone marrow aspirat
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): Stage 1: Overall response rate (CR+CRu+PR) to select adequate subtypes for Stage 2 testing Stage 2: Progression-free survival based on 1999 IWRC ; Main Objective: Stage 1 • To select adequate (e.g., p-value <0.15 in favor of lenalidomide) subtype(s) for Stage 2. Germinal center B-cell (GCB), non-GCB, both subtypes, or neither subtype will be selected based on the overall response rate (ORR) in the individual subtype to lenalidomide monotherapy versus single agent of Investigator’s choice. Stage 2 • To compare the progression free survival (PFS) of lenalidomide monotherapy versus single agent of Investigator’s choice in the subtype(s) selected in Stage 1. ; Secondary Objective: Evaluate concordance between IHC assays for stratification of GCB and non-GCB to gene expression profiles Investigate potential predictive biomarkers of clinical response or resistance to lenalidomide Investigate mechanistic biology parameters Determine efficacy using the 2007 Revised Response Criteria for Malignant Lymphoma with FDG-PET (Cheson 2007) For full secondary objectives, please see protocol. ; Timepoint(s) of evaluation of this end point: Stage 1: Treatment effect on best response will be evaluated after all 50 patients in a particular biomarker -defined subtype complete four cycle of treatment or have discontinued prior to four cycles of treatment Stage 2: 1 year from 122 pts. enrolled | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Stage 2, key ranked: 1. Complete response (CR+CRu) rate 2. Overall Response rate (CR+CRu+PR) 3. Duration of response (CR+CRu+PR) 4. Overall survival (OS) Stage 2, unranked: - Duration of complete response (CR+CRu) - Overall response rate for patients with a duration of response lasting = 16 weeks - Time to progression (TTP) - Safety - Health-related Quality of Life by using EORTC QLQ-C30 and EQ-5D ; Timepoint(s) of evaluation of this end point: 1. Complete response (CR+CRu) rate: 1 Year from 122 pts. enrolled 2. Overall Response rate (CR+CRu+PR): 1 Year from 122 pts. enrolled 3. Duration of response (CR+CRu+PR): 1 Year from 122 pts. enrolled 4. Overall survival (OS): at the time of PFS analysis and at the end of the follow-up phase - Duration of complete response (CR+CRu): 1 Year from 122 pts. enrolled - Overall response rate for patients with a duration of response lasting = 16 weeks: 1 Year from 122 pts. enrolled - Time to progression (TTP): Up to four years from last patient randomized - Safety: Up to 4 years from last patient randomised - Health-related Quality of Life by using EORTC QLQ-C30 and EQ-5D: Every 8 weeks while on treatment | — |
Countries
Australia, Austria, Czech Republic, France, Italy, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Trial Disclosure
Celgene Corporation
Outcome results
None listed