Clinical Trial: High Dose Rituximab for Initial Treatment of Indolent B-Cell Lymphomas

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

Official Title: Phase II Trial of Increased Dose Rituximab Plus Maintenance Rituximab for Initial Systemic Treatment of Indolent B-Cell Lymphomas

Brief Summary: 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.

Detailed Summary:

  • 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.

Sponsor: Massachusetts General Hospital

Current Primary Outcome: Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas [ Time Frame: after a median number of 8 maintenance cycles ]

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


Original Primary Outcome: Determine complete response rate of increased dose rituximab in indolent B-cell lymphomas [ Time Frame: 3 years ]

Current Secondary Outcome:

  • Overall Response Rate (ORR) [ Time Frame: after a median number of 8 maintenance cycles ]

    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.

  • Progression-free Survival (PFS) [ Time Frame: 5 years ]

    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.
  • Incidence of Severity of Infusion Reactions, Infections and Neutropenia [ Time Frame: 24 months ]
    Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening


Original Secondary Outcome:

  • Overall response rate [ Time Frame: 3 years ]
  • Progression-free survival [ Time Frame: 3 years ]
  • Pharmacokinetics of increased dose rituximab [ Time Frame: 3 years ]
  • Pharmacodynamics of B cell depletion [ Time Frame: 3 years ]
  • Incidence of Severity of Infusion Reactions, Infections and Neutropenia [ Time Frame: 3 years ]
  • Duration of hypogammaglobulinemia [ Time Frame: 3 years ]


Information By: Massachusetts General Hospital

Dates:
Date Received: May 6, 2009
Date Started: July 2009
Date Completion:
Last Updated: March 29, 2017
Last Verified: March 2017