Rituximab, Lenalidomide, and Bortezomib in Mantle Cell Lymphoma

This study is ongoing, but not recruiting participants.
Millennium Pharmaceuticals, Inc.
Celgene Corporation
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
First received: March 4, 2008
Last updated: April 30, 2015
Last verified: April 2015
This is a Phase I/II multicenter, open-label, dose-escalation study of rituximab, bortezomib, and lenalidomide in the first-line or second-line treatment of patients with Mantle Cell Lymphoma (MCL).

Condition Intervention Phase
Mantle Cell Lymphoma
Drug: Rituximab
Drug: Bortezomib
Drug: Lenalidomide
Phase 1
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: Phase I/II Study Evaluating Rituximab, Lenalidomide, and Bortezomib in the First-Line or Second-Line Treatment of Patients With Mantle Cell Lymphoma

Resource links provided by NLM:

Further study details as provided by SCRI Development Innovations, LLC:

Primary Outcome Measures:
  • Number of patients with dose-limiting toxicities as a measure of safety and tolerability [ Time Frame: every 3 weeks, projected 18 months ] [ Designated as safety issue: Yes ]
    The maximum tolerated dose (MTD) of lenalidomide combined with bortezomib and rituximab will be determined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity according to the NCI CTCAE v. 4.03..

Secondary Outcome Measures:
  • Progression Free Survival (PFS) [ Time Frame: every 3 weeks until treatment discontinuation then every 3 months thereafter, projected average 24 months ] [ Designated as safety issue: No ]
    Measured from Day 1 of study drug administration to disease progression or death on study.

  • Duration of Response (DoR) [ Time Frame: every 3 weeks until treatment discontinuation, expected average 18 months ] [ Designated as safety issue: No ]
    Defined as time from first date of complete or partial response (CR or PR) to disease progression or death as defined by RECIST v1.1 criteria.

  • Overall Survival (OS) [ Time Frame: every 3 weeks until treatment discontinuation then every 3 months thereafter, projected average 24 months ] [ Designated as safety issue: No ]
    Measured from Day 1 of study drug administration to date of death from any cause.

Enrollment: 39
Study Start Date: June 2008
Estimated Study Completion Date: December 2015
Primary Completion Date: April 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: rituximab/bortezomib/lenalidomide

Patients in Phase I & II will receive treatment with rituximab, bortezomib and lenalidomide in 21-day cycles.

Phase I: patients in Cohort 1 will receive Dose Level 1:

  • Cycle 1: rituximab 375 mg/m2 intravenously (IV) on Days 1, 8, 15; bortezomib 1.3 mg/ m2 SC on Days 1, 4, 8, 11; lenalidomide 15 mg by mouth (PO) daily on Days 1-14.
  • Cycles 2-6: rituximab 375 mg/m2 IV on Day 1; bortezomib 1.3 mg/ m2 SC on Days 1, 4, 8, 11; lenalidomide 15 mg PO daily on Days 1-14.

Doses will be escalated in subsequent cohorts as per protocol; doses may be de-escalated if necessary. Patients in Phase II will be treated with the DL-1 dose determined in Phase I. If patients experience no treatment-related AEs after 2 cycles, the treating physician has the option of escalating to DL1 for subsequent cycles.

Drug: Rituximab
Other Names:
  • Rituxan
  • MabThera
Drug: Bortezomib
Other Name: Velcade
Drug: Lenalidomide
Other Name: Revlimid

Detailed Description:

The combination of lenalidomide with bortezomib has not been studied in patients with MCL, but feasibility and tolerability has been demonstrated in patients with multiple myeloma. Thus, almost every 2-drug combination of rituximab, lenalidomide, and bortezomib has been tested, or is being tested. We hypothesize that all three drugs are important in MCL, and therefore propose to combine all 3 agents (rituximab, bortezomib, and lenalidomide) in a schedule that is convenient to lymphoma patients.

Approximately 18 patients may be enrolled in the Phase I portion of the study. Approximately 45 patients are planned for enrollment in Phase II.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. All study participants must be registered into the Mandatory Revllimid Risk Evaluation and Mitigation Strategies (REMS) Program, and be willing and able to comply with the requirements of the REMS program.
  2. Histology: biopsy-proven mantle cell lymphoma (MCL).
  3. Prior therapy: both newly diagnosed patients and relapsed or refractory patients who have received one prior therapy are eligible. Patients who have previously received high-dose chemotherapy with peripheral stem cell support are eligible. Newly diagnosed patients are eligible for the Phase II portion of the study only.
  4. Presence of at least one lymph node evaluable or mass measurable for response.
  5. Platelets > 75,000/µL and absolute neutrophil count (ANC) > 1,000/µL within 14 days of study registration (unless the treating physician deems the neutropenia is related to bone marrow involvement, then an ANC of > 750/mm3 is allowed).
  6. Renal fnction assessed by calculated creatinine clearance between ≥ 30 ml/min and ˂60ml/min by the Cockcroft-Gault method within 14 days of study registration:
  7. ECOG performance of 0, 1, or 2.
  8. Recovery from any previous treatment therapy.
  9. Females of childbearing potential (FCBP) must adhere to the scheduled pregnancy testing required in the Revlimid REMS® program, must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 14 days prior and again within 24 hours of starting lenalidomide for Cycle 1 (prescriptions must be filled within 7 days as required by Revlimid REMS Program) and 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.
  10. All study participants must be registered into the mandatory Revlimid REMS® program, and be willing and able to comply with the requirements of Revlimid REMS® program.
  11. Ability to understand and willingness to voluntarily sign a written informed consent document before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

Exclusion Criteria:

  1. Patient has 1.5 x ULN total bilirubin.
  2. Peripheral neuropathy ≥ CTCAE grade 2.
  3. Pregnant or breastfeeding females. (Lactating females must agree not to breastfeed while taking lenalidomide.)
  4. Thrombolic or embolic events (such as a cerebrovascular accident, including transient ischemic attacks) within the past 6 months.
  5. Pulmonary hemorrhage/bleeding event less than or equal to CTCAE grade 2 within 28 days of the first dose of study drug.
  6. Female patients who have a positive serum pregnancy test during the screening period, or a positive urine pregnancy test on DAY 1 before first dose of study drug, if applicable.
  7. Thrombolic or embolic events (such as a cerebrovascular accident, including transient ischemic attacks) within the past 6 months.
  8. Pulmonary hemorrhage/bleeding event ≥ CTCAE grade 2 within 28 days of the first dose of study drug.
  9. Any other hemorrhage/bleeding event ≥ CTCAE grade 3 ≤ 28 days of the first dose of study drug
  10. Known brain metastasis. Patients with neurological symptoms must undergo a CT scan/MRI of the brain to exclude brain metastasis.
  11. Central nervous system (CNS) involvement by lymphoma at time of enrollment.
  12. Other medical conditions or psychiatric illness that would potentially interfere with patient participation in this trial.
  13. A second malignancy, other than basal cell carcinoma of the skin or in situ carcinoma of the cervix, unless the tumor was treated with curative intent at least 2 years previously.
  14. Previous evidence of hypersensitivity to bortezomib, boron, mannitol, thalidomide, (and development of erythema nodosum if characterized by a desquamating rash), or rituximab (true anaphylaxis, not a rituximab-infusion reaction).
  15. Known human immunodeficiency virus (HIV) infection or chronic hepatitis A, B, or C. Patients who are HIV positive or who are positive for chronic hepatitis A, B, or C will be excluded due to increased risk for bone marrow suppression and other toxicities.
  16. Active, clinically serious infection > CTCAE grade 2. Patients may be eligible upon resolution of the infection.
  17. Evidence or history of bleeding diathesis or coagulopathy.
  18. Major surgery, open biopsy, or significant traumatic injury within 28 days of the first dose of study drug.
  19. Use of any other standard chemotherapy, radiation therapy, or experimental drug for the treatment of MCL within 28 days of starting treatment.
  20. Any condition that impairs a patient's ability to swallow whole pills. Impairment of gastrointestinal function (GI) or GI disease that may significantly alter the absorption of lenalidomide (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome, or small bowel resection).
  21. Patients with grade 3/4 cardiac problems, as defined by the New York Heart Association (NYHA) criteria or any of the following:

    • History of uncontrolled or symptomatic angina
    • History of arrhythmias requiring medications, or clinically significant, with the exception of asymptomatic atrial fibrillation requiring anticoagulation
    • Myocardial infarction < 6 months from study entry
    • Uncontrolled or symptomatic congestive heart failure
    • Ejection fraction below the institutional normal limit
    • Electrocardiographic evidence of acute ischemia or active conduction system
    • Any other cardiac condition that, in the opinion of the treatment physician, would make this protocol unreasonably hazardous for the patient

21. Uncontrolled hypertension (systolic blood pressure [BP] > 180 or diastolic BP > 100mm Hg) or uncontrolled cardiac arrhythmias.

22. Any prior use of lenalidomide.

  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: NCT00633594

United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
RHHP/ Hope Cancer Center
Terre Haute, Indiana, United States, 47802
United States, Missouri
St. Louis Cancer Care
Chesterfield, Missouri, United States, 63017
United States, New Jersey
Hematology-Oncology Associates of Northern NJ
Morristown, New Jersey, United States, 07960
United States, Ohio
Oncology Hematology Care Inc.
Cincinnati, Ohio, United States, 45242
United States, Tennessee
Chattanooga Oncology Hematology Associates
Chattanooga, Tennessee, United States, 37404
Tennessee Oncology, PLLC
Nashville, Tennessee, United States, 37023
Sponsors and Collaborators
SCRI Development Innovations, LLC
Millennium Pharmaceuticals, Inc.
Celgene Corporation
Study Chair: Ian W Flinn, M.D. SCRI Development Innovations, LLC
  More Information

No publications provided

Responsible Party: SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier: NCT00633594     History of Changes
Other Study ID Numbers: SCRI LYM 58
Study First Received: March 4, 2008
Last Updated: April 30, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by SCRI Development Innovations, LLC:
Mantle Cell Lymphoma
Phase 1/2

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

ClinicalTrials.gov processed this record on November 24, 2015