Clinical Trial: Rituximab, Lenalidomide, and Bortezomib in Mantle Cell Lymphoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary: 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).

Detailed Summary:

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.


Sponsor: SCRI Development Innovations, LLC

Current Primary Outcome:

  • Maximum Tolerated Dose of Lenalidomide Combined With Bortezomib and Rituximab in Phase I Participants [ Time Frame: Collected from day of first dose to the end of the first treatment cycle, up to 21 days ]

    Determination of the maximum tolerated dose (MTD) of lenalidomide combined with bortezomib and rituximab, defined as the highest dose at which ≤1 of 6 patients experiences a dose-limiting toxicity according to the NCI CTCAE v. 4.03.

    MTD of Lenalidomide was tested, included with 1.3 mg/m2 subcutaneous (D1, 4, 8, 11) bortezomib, 375 mg/m2 (D1, 8, 15 of Cycle 1, D1 on subsequent cycles) rituximab.

    Three dose limiting toxicities were reported in two patients (grade 4 neutropenia and grade 3 neuropathy, grade 3 rash)

  • Incidence of Non-Serious Adverse Events as a Measure of Safety and Tolerability, Phase II [ Time Frame: Collected from day of first dose to 30 days after the last dose of study medication, a maximum of 18 weeks and 30 days after last study treatment ]

    A count of affected participants with non-serious adverse events (regardless of relationship to study treatments) occurring in >= 15% of treated patients enrolled in the Phase II section of the study.

    Lenalidomide DL-1 dose (10 mg orally, once daily (PO QD)) Day 1-14 followed by 7 days of rest, Rituximab 375 mg/m2 IV Days 1, 8, and 15 of Cycle 1; Cycles 2-6: 375 mg/m2 IV Day 1, Bortezomib 1.3 mg/m2 subcutaneous Days 1, 4, 8, and 11 for Cycles 1-6



Original Primary Outcome:

  • To determine the maximum tolerated dose (MTD) of the combination of lenalidomide, bortezomib, and rituximab in patients with relapsed or refractory mantle cell lymphoma (MCL) who have received one prior therapy. [ Time Frame: 18 months ]
  • To determine the safety and tolerability of the combination of lenalidomide, bortezomib, and rituximab in patients with previously untreated MCL and patients with relapsed or refractory MCL who have received one prior therapy [ Time Frame: 18 months ]


Current Secondary Outcome:

  • Overall Response Rate (ORR) of Phase I and Phase II Participants [ Time Frame: Every 6 weeks until treatment discontinuation then every 3 months thereafter, projected average 24 months ]
    Response to treatment (Complete Response (CR) or Partial Response (PR)) determined using Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses, no increase in the size of other nodes, liver or spleen, no new sites of disease, patients who achieve CR but have persistent morphologic bone marrow involvement; Stable Disease (SD): failing to attain PR or CR, but not fulfilling criteria for progressive disease; Progressive Disease (PD)/Relapse: appearance of new lesions more than 1.5 cm in any axis, 50% or greater increase from nadir SPD of any previously involved sites, 50% or greater increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in short axis.
  • Overall Response Rate (ORR) of Previously Treated and Previously Untreated Participants [ Time Frame: Every 6 weeks until treatment discontinuation then every 3 months thereafter, projected average 24 months ]
    Response to treatment (Complete Response (CR) or Partial Response (PR)) determined using Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of all detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of the product of the diameters (SPD) of up to 6 of the largest dominant nodes or extranodal masses, no increase in the size of other nodes, liver or spleen, no new sites of disease, patients who achieve CR but have persistent morphologic bone marrow involvement; Stable Disease (SD): failing to attain PR or CR, but not fulfilling criteria for progressive disease; Progressive Disease (PD)/Relapse: appearance of new lesions more than 1.5 cm in any axis, 50% or greater increase from nadir SPD of any previously involved sites, 50% or greater increase in the longest diameter of any single previously identified node or extranodal mass more than 1 cm in short axis.
  • Time to Best Response of Phase I and Phase II Participants [ Time Frame: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years ]

    Measured from the time of study entry to the documented beginning of response (CR or PR). This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement.

    Time to Best Response will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification.

  • Time to Best Response of Previously Treated and Previously Untreated Participants [ Time Frame: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years ]
    Measured from the time of study entry to the documented beginning of response (CR or PR). This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement.
  • Duration of Response (DoR) of Phase I and Phase II Participants [ Time Frame: Every 3 months (+/- 2 weeks) after discontinuation of study treatment for 2 years or until documented disease progression ]

    Measured from the documented beginning of response (CR or PR) to the time of relapse. This is measured in responders per Non-Hodgkin's Lymphoma Revised Response Criteria for Malignant Lymphoma (Cheson et al. 2007.) CR: complete disappearance of detectable clinical evidence of disease and disease-related symptoms; PR: 50% or greater decrease in sum of product of diameters (SPD) of up to 6 of the largest dominant nodes or nodal masses, no increase in size of other nodes, liver or spleen, no new disease sites, patients with CR and persistent morphologic bone marrow involvement.

    Duration of Response will be examined using time-to-event analysis methods. Kaplan-Meier figures will be generated and the log-rank test will be used to examine differences existing between various levels of stratification.

  • Duration of Response (DoR) of Previously Treated and Previously

    Original Secondary Outcome:

    • To make preliminary estimates of the efficacy of the combination of lenalidomide, bortezomib, and rituximab in patients with previously untreated MCL and patients with relapsed or refractory MCL who have received one prior therapy. [ Time Frame: 18 months ]
    • To determine time to best response, duration of response, progression-free survival (PFS), and overall survival. [ Time Frame: 18 months ]


    Information By: SCRI Development Innovations, LLC

    Dates:
    Date Received: March 4, 2008
    Date Started: June 2008
    Date Completion:
    Last Updated: December 6, 2016
    Last Verified: December 2016