Lenalidomide Plus Rituxan for Untreated Mantle Cell Lymphoma

Sponsor
Weill Medical College of Cornell University (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT01472562
Collaborator
Celgene (Industry)
38
Enrollment
4
Locations
1
Arm
134.1
Anticipated Duration (Months)
9.5
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or DiseaseIntervention/TreatmentPhase
Phase 2

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
38 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase II Study of Lenalidomide Plus Rituximab in Patients With Previously Untreated Mantle Cell Lymphoma
Actual Study Start Date :
Jul 29, 2011
Actual Primary Completion Date :
Apr 1, 2014
Anticipated Study Completion Date :
Oct 1, 2022

Arms and Interventions

ArmIntervention/Treatment
Experimental: all patients

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.

Drug: lenalidomide
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.
Other Names:
  • revlimid
  • Biological: rituximab
    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.
    Other Names:
  • rituxan
  • Outcome Measures

    Primary Outcome Measures

    1. 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 Outcome Measures

    1. Progression-free Survival [10 years]

      PFS will be defined as the time from first treatment day until objective or symptomatic progression or death.

    2. Overall Survival [10 years]

      Overall survival will be defined as the time from first treatment day until death.

    3. Time to Next Treatment [10 years]

      Median amount of time (in months) from start of study treatment to next treatment

    4. Safety as Measured by Number of Subjects Who Experience an Adverse Event While on Study Treatment [10 years]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts 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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Moffitt Cancer CenterTampaFloridaUnited States33612
    2University of ChicagoChicagoIllinoisUnited States60637
    3Weill Cornell Medical CollegeNew YorkNew YorkUnited States10065
    4University of PennsylvaniaPhiladelphiaPennsylvaniaUnited States19104

    Sponsors and Collaborators

    • Weill Medical College of Cornell University
    • Celgene

    Investigators

    • Principal Investigator: Jia Ruan, MD, PhD, Weill Medical College of Cornell University

    Study Documents (Full-Text)

    None provided.

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    Weill Medical College of Cornell University
    ClinicalTrials.gov Identifier:
    NCT01472562
    Other Study ID Numbers:
    • 1103011566
    First Posted:
    Nov 16, 2011
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Mar 1, 2022
    Keywords provided by Weill Medical College of Cornell University
    Additional relevant MeSH terms:

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group TitleAll Patients
    Arm/Group DescriptionStudy Treatment Arm
    Period Title: Induction Phase (Week 1- 48)
    STARTED38
    COMPLETED27
    NOT COMPLETED11
    Period Title: Induction Phase (Week 1- 48)
    STARTED27
    COMPLETED4
    NOT COMPLETED23

    Baseline Characteristics

    Arm/Group TitleAll Patients
    Arm/Group DescriptionStudy Treatment Arm
    Overall Participants38
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    65
    Sex: Female, Male (Count of Participants)
    Female
    11
    28.9%
    Male
    27
    71.1%

    Outcome Measures

    1. Primary Outcome
    TitleOverall Response Rate
    DescriptionThe primary endpoint of overall response rate will be estimated and a 95% confidence interval will be estimated via binomial proportions.
    Time Frame30 months

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group TitleAll Patients
    Arm/Group DescriptionStudy Treatment Arm
    Measure Participants33
    Number (95% Confidence Interval) [percentage of patients]
    92
    2. Secondary Outcome
    TitleProgression-free Survival
    DescriptionPFS will be defined as the time from first treatment day until objective or symptomatic progression or death.
    Time Frame10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    3. Secondary Outcome
    TitleOverall Survival
    DescriptionOverall survival will be defined as the time from first treatment day until death.
    Time Frame10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    4. Secondary Outcome
    TitleTime to Next Treatment
    DescriptionMedian amount of time (in months) from start of study treatment to next treatment
    Time Frame10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description
    5. Secondary Outcome
    TitleSafety as Measured by Number of Subjects Who Experience an Adverse Event While on Study Treatment
    Description
    Time Frame10 years

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title
    Arm/Group Description

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group TitleAll Patients
    Arm/Group DescriptionStudy Treatment Arm
    All Cause Mortality
    All Patients
    Affected / at Risk (%)# Events
    Total/ (NaN)
    Serious Adverse Events
    All Patients
    Affected / at Risk (%)# Events
    Total11/38 (28.9%)
    Blood and lymphatic system disorders
    Tumor Flare2/38 (5.3%) 2
    Blood Bilirubin Increase1/38 (2.6%) 1
    Cardiac disorders
    Ventricular Fibrillation1/38 (2.6%) 1
    Gastrointestinal disorders
    Cholangitis1/38 (2.6%) 1
    General disorders
    Fever1/38 (2.6%) 1
    Pneumonia2/38 (5.3%) 2
    Shortness of Breath1/38 (2.6%) 1
    Hepatobiliary disorders
    Cholecystitis1/38 (2.6%) 1
    Injury, poisoning and procedural complications
    Hip Fracture1/38 (2.6%) 1
    Infusion Reaction1/38 (2.6%) 1
    Skin and subcutaneous tissue disorders
    Basal Cell Carcinoma1/38 (2.6%) 1
    Melanoma1/38 (2.6%) 1
    Merkel Cell Carcinoma1/38 (2.6%) 1
    Pruritic Rash1/38 (2.6%) 1
    Other (Not Including Serious) Adverse Events
    All Patients
    Affected / at Risk (%)# Events
    Total31/38 (81.6%)
    Blood and lymphatic system disorders
    Thrombocytopenia15/38 (39.5%)
    Leukopenia23/38 (60.5%)
    Neutropenia28/38 (73.7%)
    Blood Bilirubin Increased9/38 (23.7%)
    Anemia23/38 (60.5%)
    Neutropenic Fever2/38 (5.3%)
    Tumor Flare13/38 (34.2%)
    Cardiac disorders
    Hypertension6/38 (15.8%)
    Endocrine disorders
    Hypothyroidism6/38 (15.8%)
    Hyperthyroidism3/38 (7.9%)
    Gastrointestinal disorders
    Constipation17/38 (44.7%)
    Diarrhea21/38 (55.3%)
    General disorders
    Nausea12/38 (31.6%)
    Vomit5/38 (13.2%)
    Fever22/38 (57.9%)
    Fatigue28/38 (73.7%)
    Night Sweats9/38 (23.7%)
    Dyspnea11/38 (28.9%)
    Sore Throat9/38 (23.7%)
    Cough21/38 (55.3%)
    Abdominal Pain9/38 (23.7%)
    Head Pain/Headache/Migraine10/38 (26.3%)
    Rigors4/38 (10.5%)
    Edema16/38 (42.1%)
    Chills5/38 (13.2%)
    Serum Sickness3/38 (7.9%)
    Hepatobiliary disorders
    Elevated Alanine Aminotransferase13/38 (34.2%)
    Elevated Aspartate Aminotransferase11/38 (28.9%)
    Elevated Alkaline Phosphatase9/38 (23.7%)
    Metabolism and nutrition disorders
    Anorexia11/38 (28.9%)
    Hypoalbuminemia13/38 (34.2%)
    Hyperalbuminemia13/38 (34.2%)
    Hypocalcemia17/38 (44.7%)
    Hyponatremia12/38 (31.6%)
    Hypomagnesemia9/38 (23.7%)
    Hyperkalemia3/38 (7.9%)
    Hypoglycemia13/38 (34.2%)
    Hyperglycemia19/38 (50%)
    Musculoskeletal and connective tissue disorders
    Arthralgia10/38 (26.3%)
    Myalgia7/38 (18.4%)
    Cramping6/38 (15.8%)
    Gout Flares4/38 (10.5%)
    Nervous system disorders
    Dysgeusia7/38 (18.4%)
    Dizziness8/38 (21.1%)
    Neuropathy6/38 (15.8%)
    Tinnitus5/38 (13.2%)
    Product Issues
    Infusion Related Reaction13/38 (34.2%)
    Renal and urinary disorders
    Urinary tract Infection7/38 (18.4%)
    Elevated Creatinine8/38 (21.1%)
    Respiratory, thoracic and mediastinal disorders
    Upper Respiratory Infection15/38 (39.5%)
    Pneumonia3/38 (7.9%)
    Bronchial Infection/ Lung Infection5/38 (13.2%)
    Skin and subcutaneous tissue disorders
    Nasal Congestion12/38 (31.6%)
    Macro Papular25/38 (65.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/TitleJia Ruan M.D, Ph.D
    OrganizationWeill Cornell Medicine
    Phone646.962.2064
    Emailamr2017@med.cornell.edu
    Responsible Party:
    Weill Medical College of Cornell University
    ClinicalTrials.gov Identifier:
    NCT01472562
    Other Study ID Numbers:
    • 1103011566
    First Posted:
    Nov 16, 2011
    Last Update Posted:
    Mar 29, 2022
    Last Verified:
    Mar 1, 2022