The purpose of this clinical trial is to see if increased doses of rituximab are safe and effective for the initial treatment of indolent B-cell lymphomas. Rituximab (Rituxan) is a type of drug called an "antibody" that specifically targets B-cell lymphoma cells, and is approved by the FDA for the treatment of indolent B-cell non-hodgkin lymphomas and certain other types of non-hodgkin lymphomas. Standard doses currently used may not be achieving maximal efficacy. Higher doses have been shown to be safe in other clinical trials, and may offer superior efficacy to the current standard dose. This trial also employs intermittent maintenance doses of rituximab at the standard dose, which has been shown to prolong remissions and survival in patients with relapsed indolent B-cell lymphomas. This trial is designed to show that higher dose rituximab plus maintenance rituximab can achieve similarly good results to chemotherapy approaches, but without chemotherapy-related toxicity.
* All participants will receive increased-dose rituximab through a vein in the arm once a week for 4 weeks (on Days 1, 8, 15, and 22 of the initial 28-day study cycle). This first cycle of study treatment is called the Induction Phase. If the participant responds well to the Induction Phase, they then may continue to the Maintenance Therapy Phase, where they will receive a lower dose of rituximab once every three months for up to 2 years. * During the Induction Phase, the following procedures will take place before the participant receives each dose of rituximab: medical review, physical exam, performance status, and ECG. Blood tests will be drawn about 30-60 minutes after the first dose of rituximab on Day 1. Samples will be drawn immediately before each dose and again 30-60 minutes after each dose on Days 1, 8, 15 and 22. * During the Maintenance Therapy Phase, the following procedures will take place before the participant receives each dose of rituximab: medical review, physical exam, performance status, ECG, blood tests and response assessments by CT scan.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Increased dose (750 mg/m2) intravenously for 4 weekly doses followed by maintenance dosing once every three months for up to 2 years. Maintenance dose is standard (375 mg/m2).
Massachusetts General Hospital
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
Boston, Massachusetts, United States
Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas
CR requires all of the following: 1. Regression to normal size on CT (≤ 1.5 cm in their greatest transverse diameter for nodes ≥ 1.5 cm before therapy). Previously involved nodes that were 1.1 to 1.5 cm in their greatest transverse diameter before treatment must have decreased to \<1 cm in their greatest transverse diameter after treatment, or by more than 75% in the sum of the products of the greatest diameters (SPD). 2. The spleen, if considered to be enlarged before therapy on the basis of a CT scan, must have regressed in size and must not be palpable on physical examination. 3. If bone marrow is known to be involved at the beginning, then repeat biopsy documents clearance
Time frame: after a median number of 8 maintenance cycles, up to 24 weeks
Overall Response Rate (ORR)
Complete Response (CR): see definition in primary outcome Partial Response (PR): 1. ≥50% decrease in SPD of up to 6 largest dominant masses 2. No new sites of disease or increase in the size of the other nodes, liver, or spleen. 3. Splenic and hepatic nodules must regress by at least 50% in the SPD. Overall Response (OR) = CR + PR.
Time frame: after a median number of 8 maintenance cycles, up to 24 weeks
Progression-free Survival (PFS)
Progressive Disease (PD) or Relapsed Disease (RD): 1. Appearance of a new lesion(s) \> 1.5 cm in any axis, ≥ 50% increase in SPD of more than one node, or ≥50% increase in longest diameter of a previously identified node \> 1 cm in short axis. 2. \>50% increase from nadir in the SPD of any previous lesions PFS is number of participants who have not died or had PD or RD.
Time frame: 5 years
Incidence of Severity of Infusion Reactions, Infections and Neutropenia
Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening
Time frame: 24 months
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