Clinical trial NCT01125293
Conditions: Waldenstrom's Macroglobulinemia
Keywords: everolimus rituximab bortezomib RAD001 Rituxan Velcade
Sponsor: Dana-Farber Cancer Institute
Start date: 2010-04-01; Completion date: 2014-08-01
Enrollment: 46 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this research study is to test the safety of the combination of everolimus, rituximab and bortezomib. Everolimus is a drug that works by preventing cells in your body from growing and dividing. Information from basic and other clinical research suggests that everolimus may also inhibit tumor growth in people with relapsed or refractory lymphoma. The FDA has approved everolimus for the treatment of multiple myeloma, a cancer that is closely related to Waldenstrom's Macroglobulinemia. Rituximab is approved by the FDA for the treatment of non-Hodgkin's lymphoma, which included Waldenstrom's Macroglobulinemia.

Funding Source - FDA OOPD

Detailed description:
Study Design

This is a phase I/II study. The phase I portion of the study will determine the maximum tolerated dose of everolimus, rituximab, and bortezomib combination, while the phase II portion will evaluate the depth of responses to the everolimus, rituximab, and bortezomib combination. If patients show response, they will continue on therapy for a total of 6 cycles, and then go on maintenance therapy with everolimus alone until progression. Patients on maintenance will be monitored every 3 months for response. Because of the potential of an IgM flare after rituximab, patients who show an increase in IgM after rituximab in the first 3 months will not be deemed as having progressive disease unless they show evidence of clinical progression and not just an increase of IgM levels. If biochemical progression is confirmed by m-spike, but the participant is clinically benefitting from therapy, the participant may continue on treatment for a few additional points of assessment and re-discuss benefit of therapy. Additionally, if the participant progressed because the treatment was held, participant may remain on study at the discretion of the overall Principal Investigator. Relapse from CR is defined by the reappearance of monoclonal IgM protein and/or recurrence of bone marrow involvement, lymphadenopathy/splenomegaly or symptoms attributable to active disease (Owen et al., 2012). Progression from PR is defined by ≥ 25% increase in IgM level from lowest recorded value and confirmed by a repeat assessment. The development of new signs and symptoms of disease, including Bing Neel syndrome and histological transformation, is also considered as evidence of disease progression. An absolute increase of at least 5 g/l is required to define progression when the IgM level is the only applicable criterion (Owen et al., 2012).

Arms: arm 1: Combination of everolimus \& rituximab for 6 cycles:

Everolimus 5 mg: Taken orally on a daily basis x 28 days

Rituximab 375 mg/Kg: Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only

(1 cycle = 28 days)

Maintenance:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

(1 cycle = 28 days)

Participants are treated on everolimus maintenance until progression, unacceptable toxicity or withdrawal for other reasons. arm 2: Combination of everolimus \& rituximab for 6 cycles:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

Rituximab 375 mg/Kg: Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only

(1 cycle = 28 days)

Maintenance:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

(1 cycle = 28 days)

Participants are treated on everolimus maintenance until progression, unacceptable toxicity or withdrawal for other reasons. arm 3: Combination of everolimus \& rituximab with bortezomib for 6 cycles:

Everolimus 5 mg: Taken orally on a daily basis x 28 days

Rituximab 375 mg/Kg: Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only

Bortezomib 1.6 mg/m\^2: Given intravenously on days 1, 8 and 15 of every cycle (1 cycle = 28 days)

Maintenance:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

(1 cycle = 28 days)

Participants are treated on everolimus maintenance until progression, unacceptable toxicity or withdrawal for other reasons. arm 4: Combination of everolimus \& rituximab with bortezomib for 6 cycles:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

Rituximab 375 mg/Kg: Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only

Bortezomib 1.6 mg/m\^2: Given intravenously on days 1, 8 and 15 of every cycle

(1 cycle = 28 days)

Maintenance:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

(1 cycle = 28 days)

Participants are treated on everolimus maintenance until progression, unacceptable toxicity or withdrawal for other reasons. arm 5: Combination of everolimus \& rituximab with bortezomib for 6 cycles:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

Rituximab 375 mg/Kg: Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only

Bortezomib 1.6 mg/m\^2: Given intravenously on days 1, 8 and 15 of every cycle

(1 cycle = 28 days)

Maintenance:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

(1 cycle = 28 days)

Participants are treated on everolimus maintenance until progression, unacceptable toxicity or withdrawal for other reasons. arm 6: Combination of everolimus \& rituximab with bortezomib for 6 cycles:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

Rituximab 375 mg/Kg: Given intravenously on days 1, 8, 15 and 22 of Cycle 1 and Cycle 4 only

Bortezomib 1.6 mg/m\^2: Given intravenously on days 1, 8 and 15 of every cycle

Maintenance:

Everolimus 10 mg: Taken orally on a daily basis x 28 days

(1 cycle = 28 days)

Participants are treated on everolimus maintenance until progression, unacceptable toxicity or withdrawal for other reasons.
Interventions: intervention 1: Everolimus intervention 2: Rituximab intervention 3: Bortezomib
Intervention descriptions: intervention 1: None intervention 2: None intervention 3: None

Protocol documents: