Mantle Cell Lymphoma
Conditions
Keywords
mantle cell lymphoma
Brief summary
This is a phase II, multicenter study to determine the efficacy and safety of first-line lenalidomide plus rituximab therapy in patients with mantle cell lymphoma who have received no prior systemic therapy.
Detailed description
Induction Phase (week 1 - 48): * Lenalidomide will be given at 20 mg/day for days 1-21 of a 28-day cycle for 12 cycles. If no excess toxicity is observed the dose will be increased to 25 mg/day. * Rituximab will be administered at 375 mg/m2 per dose for a total of 9 doses. The first 4 doses will be administered weekly starting on day 1 of lenalidomide (e.g. days 1, 8, 15 and 22). Subsequent rituximab doses will be administered for one dose each at weeks 12, 20, 28, 36 and 44. Maintenance Phase (week 49 - progression of disease): * Lenalidomide will be given at 15 mg/day for days 1-21 of a 28-day cycle. * Rituximab at 375 mg/m2 per dose will be administered for one dose every 8 weeks, starting at week 52. Response Assessment * Year 1-2: Conventional restaging CT scan (or MRI) with IV contrast every 3 months from cycle 1 day 1 of the study. * Year 3 onwards: Conventional restaging CT scan (or MRI) with IV contrast every 6 months until progression.
Interventions
DRUGlenalidomide
Induction phase: 20 mg/day for days 1-21 of a 28-day cycle for 12 cycles. If no excess toxicity is observed the dose will be increased to 25 mg/day. Maintenance phase: Lenalidomide will be given at 15 mg/day for days 1-21 of a 28-day cycle.
BIOLOGICALrituximab
Induction phase: Rituximab will be administered at 375 mg/m2 per dose for a total of 9 doses. The first 4 doses will be administered weekly starting on day 1 of lenalidomide (e.g. days 1, 8, 15 and 22). Subsequent rituximab doses will be administered for one dose each at weeks 12, 20, 28, 36 and 44. Maintenance phase: Rituximab at 375 mg/m2 per dose will be administered for one dose every 8 weeks, starting at week 52.
Sponsors
Celgene
Weill Medical College of Cornell University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Understand and voluntarily sign an informed consent form. * Age \> = 18 years at the time of signing the informed consent form. * Able to adhere to the study visit schedule and other protocol requirements. * Histologically confirmed diagnosis of mantle cell Non-Hodgkin's Lymphoma with cyclin D1 overexpression by immunohistochemistry, and a characteristic immunophenotypic profile with CD5(+), CD23(-), CD20(+), and CD10(-). In tumor tissues with negative cyclin D1, evidence of cyclin D2 or D3 overexpression by immunohistochemistry will be acceptable. * No prior systemic therapy for lymphoma including chemotherapy or immunotherapy. Patients may have received involved-field radiation therapy which has been discontinued at least 4 weeks prior to treatment in this study. * Patient has measurable disease as defined by a tumor mass \> 1.5 cm in one dimension. * Low and intermediate-risk disease as defined by MIPI score. * Subject who the investigator considers that chemotherapy is not indicated. * ECOG performance status of \< = 2 at study entry. * Laboratory test results within these ranges: * Absolute neutrophil count \> = 1000 /mm³ * Platelet count \> = 75,000 /mm³ * Calculated creatinine clearance ≥ 30 ml/min by Cockcroft-Gault formula • Total bilirubin \< = 2 x ULN * AST (SGOT) and ALT (SGPT) \< = 3 x ULN. * Disease free of prior malignancies for \> = 5 years with exception of currently treated basal cell, squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer. * All subjects must be registered into the mandatory RevAssist® program, and be willing and able to comply with the requirements of RevAssist®. * Subjects of reproductive potential agree to use birth control throughout their participation in this study, and for three months following study termination. * Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days and again within 24 hours prior to prescribing lenalidomide for Cycle 1 (prescriptions must be filled within 7 days). FCBP must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 28 days before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with a FCBP even if they have had a successful vasectomy. See Appendix: Risks of Fetal Exposure, Pregnancy Testing Guidelines and Acceptable Birth Control Methods. * Able to take aspirin (81 or 325 mg) daily as prophylactic anticoagulation (patients intolerant to ASA may use warfarin or low molecular weight heparin). * Asymptomatic carriers of hepatitis B virus can be considered for study if they agree to and comply with close monitoring and suppressive therapy with lamivudine during treatment and for additional six months after coming off study.
Exclusion criteria
* Any serious medical condition, laboratory abnormality, or psychiatric illness that would prevent the subject from signing the informed consent form. * Pregnant or breast feeding females. * Any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study. * Use of any other experimental drug or therapy within 28 days of baseline. * Patient on corticosteroids within two weeks prior to study entry, except for prednisone \< = 10 mg/day or equivalent for purposes other than treating MCL. * Known hypersensitivity to thalidomide. * Any prior use of lenalidomide. * Known seropositive for or active viral infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV). Patients who are seropositive because of hepatitis B virus vaccine are eligible. * Known central nervous system (CNS) involvement by lymphoma. * Patient at high risk for deep vein thrombosis not willing to take DVT prophylaxis. * Patient has had major surgery within the last 3 weeks
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | 30 months | The primary endpoint of overall response rate will be estimated and a 95% confidence interval will be estimated via binomial proportions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Progression-free Survival | 10 years | Secondary endpoints of progression-free survival (PFS), overall survival (OS), and time to the next treatment will be assessed by Kaplan-Meier survival analysis.PFS will be defined as the time from the first treatment day until objective or symptomatic progression or death. The outcome measure is the number of participants who achieved PFS. |
| Number of Participants With Overall Survival | 10 years | Secondary endpoints of progression-free survival (PFS), overall survival (OS), and time to next treatment will be assessed by Kaplan-Meier survival analysis. Overall survival will be defined as the time from first treatment day until death. The outcome measures is the number of participants who achieved OS. |
| Time to Next Treatment | 10 years | Median amount of time (in months) from start of study treatment to next treatment |
| Safety as Measured by Number of Subjects Who Experience an Adverse Event While on Study Treatment | 6 years | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Patients Study Treatment Arm | 38 |
| Total | 38 |
Baseline characteristics
| Characteristic | All Patients |
|---|---|
| Age, Continuous | 65 years |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 31 / 38 |
| serious Total, serious adverse events | 11 / 38 |
Outcome results
Primary
Overall Response Rate
The primary endpoint of overall response rate will be estimated and a 95% confidence interval will be estimated via binomial proportions.
Time frame: 30 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Overall Response Rate | 92 percentage of patients |
Secondary
Number of Participants With Overall Survival
Secondary endpoints of progression-free survival (PFS), overall survival (OS), and time to next treatment will be assessed by Kaplan-Meier survival analysis. Overall survival will be defined as the time from first treatment day until death. The outcome measures is the number of participants who achieved OS.
Time frame: 10 years
Population: We enrolled a total of 38 patients (all evaluable for safety), but only 36 were evaluable for responses. Two patients could not be evaluated because they had an inflammatory syndrome (tumor flare) during the first cycle and were withdrawn before response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Number of Participants With Overall Survival | 24 participants |
Secondary
Number of Participants With Progression-free Survival
Secondary endpoints of progression-free survival (PFS), overall survival (OS), and time to the next treatment will be assessed by Kaplan-Meier survival analysis.PFS will be defined as the time from the first treatment day until objective or symptomatic progression or death. The outcome measure is the number of participants who achieved PFS.
Time frame: 10 years
Population: We enrolled a total of 38 patients (all evaluable for safety), but only 36 were evaluable for responses. Two patients could not be evaluated because they had an inflammatory syndrome (tumor flare) during the first cycle and were withdrawn before response assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| All Patients | Number of Participants With Progression-free Survival | 21 participants |
Secondary
Safety as Measured by Number of Subjects Who Experience an Adverse Event While on Study Treatment
Time frame: 6 years
Population: We enrolled a total of 38 patients (all evaluable for safety), but only 36 were evaluable for responses. Two patients could not be evaluated because they had an inflammatory syndrome (tumor flare) during the first cycle and were withdrawn before response assessment.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| All Patients | Safety as Measured by Number of Subjects Who Experience an Adverse Event While on Study Treatment | 38 Participants |
Secondary
Time to Next Treatment
Median amount of time (in months) from start of study treatment to next treatment
Time frame: 10 years
Population: Data was not collected on this outcome measure