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

NCT00895661 | Completed Phase 2 Results DMC

• 1 other identifier: 09-054
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 2

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.

Conditions

B-cell Lymphoma; Indolent B-cell Lymphoma

Keywords

rituximab

Outcome Measures

Primary Outcomes (1)

• 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

  after a median number of 8 maintenance cycles, up to 24 weeks

Secondary Outcomes (3)

• Overall Response Rate (ORR)

  after a median number of 8 maintenance cycles, up to 24 weeks

• Progression-free Survival (PFS)

  5 years

• Incidence of Severity of Infusion Reactions, Infections and Neutropenia

  24 months

Study Arms (1)

rituximab

OTHER

single-arm, open-label, interventional

Drug: rituximab

Interventions

rituximab DRUG

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).

Also known as: Rituxan

rituximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Indolent B-Cell NHL of the following histologies:
• Follicular lymphoma (grades 1-3A);
• marginal zone lymphoma (extranodal, nodal or splenic):
• Extranodal marginal zone lymphomas (MALT lymphomas) may not be candidates for cure with antibiotics or local radiotherapy. Patients who have failed antibiotics or local therapy are eligible for the protocol as long as they have measurable disease and are naive to chemotherapy and monoclonal antibody;
• splenic marginal zone lymphoma patients may have received prior splenectomy as long as they have measureable disease and are naive to chemotherapy and monoclonal antibody therapy;
• Small lymphocytic lymphoma (must have less than 5000 circulating clonal B-lymphocytes);
• Indolent CD20+ B-cell lymphoma not otherwise specified with CD20+ expression
• Measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as 20mm or greater with conventional techniques or as 10mm or greater with spiral CT scan
• No previous chemotherapy, antibody therapy or radioimmunotherapy for NHL. Patients previously treated with external bean radiation alone, surgery, or with antibiotics are eligible
• years of age or older
• Life expectancy of greater than 3 months
• ECOG performance status of 2 or less
• Adequate bone marrow function
• Use of adequate contraception

You may not qualify if:

• Prior chemotherapy, monoclonal antibody therapy or radioimmunotherapy for lymphoma
• Receiving any other investigational agent
• Known brain metastases
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to rituximab
• HIV positivity
• Active hepatitis B infection
• Candidate for curative radiotherapy, unless radiation therapy is considered too toxic (as in abdominal disease), or is refused by the patient
• NYHA Classification III or IV disease
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection that is not optimally treated with antibiotics, unstable angina pectoris, or psychiatric illness/social situations that would limit compliance with study requirements
• Pregnant women
• Individuals with a history of a different malignancy except for the following circumstances:
• disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy;
• localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ; and
• non-melanoma skin cancers

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Dana-Farber Cancer Institute: collaborator
• Brigham and Women's Hospital: collaborator
• Genentech, Inc.: collaborator

Study Sites (2)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Lymphoma, B-Cell

Interventions

Rituximab

Condition Hierarchy (Ancestors)

Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Jeremy Abramson, MD
• Organization: Massachusetts General Hospital Cancer Center

jabramson@mgh.harvard.edu

617-724-4000

Study Officials

• Jeremy Abramson, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Lymphoma Program

Study Record Dates

• First Submitted: May 6, 2009
• First Posted: May 8, 2009
• Study Start: July 1, 2009
• Primary Completion: October 1, 2010
• Study Completion: August 1, 2015
• Last Updated: June 9, 2017
• Results First Posted: May 9, 2017

Record last verified: 2017-05

Locations

US (2)