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

Primary Purpose

B-cell Lymphoma, Indolent B-cell Lymphoma

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

rituximab

About this trial

This is an interventional treatment trial for B-cell Lymphoma focused on measuring rituximab

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Indolent B-Cell NHL of the following histologies:
1. Follicular lymphoma (grades 1-3A);
2. 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;
3. Small lymphocytic lymphoma (must have less than 5000 circulating clonal B-lymphocytes);
4. 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
18 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

Exclusion Criteria:

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:
1. disease-free for at least 1 year and are deemed by the investigator to be at low risk for recurrence of that malignancy;
2. localized prostate cancer, prostate cancer with elevated PSA but no measurable disease on CT scans or bone scan, cervical cancer in situ; and
3. non-melanoma skin cancers

Sites / Locations

Massachusetts General Hospital
Dana-Farber Cancer Institute

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

rituximab

Arm Description

single-arm, open-label, interventional

Outcomes

Primary Outcome Measures

Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas

CR requires all of the following: 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). 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. If bone marrow is known to be involved at the beginning, then repeat biopsy documents clearance

Secondary Outcome Measures

Overall Response Rate (ORR)

Complete Response (CR): see definition in primary outcome Partial Response (PR): ≥50% decrease in SPD of up to 6 largest dominant masses No new sites of disease or increase in the size of the other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD. Overall Response (OR) = CR + PR.

Progression-free Survival (PFS)

Progressive Disease (PD) or Relapsed Disease (RD): 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. >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

Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening

Full Information

NCT ID

NCT00895661

First Posted

May 6, 2009

Last Updated

May 9, 2017

Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute, Brigham and Women's Hospital, Genentech, Inc.

1. Study Identification

Unique Protocol Identification Number

NCT00895661

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2017

Overall Recruitment Status

Completed

Study Start Date

July 2009 (Actual)

Primary Completion Date

October 2010 (Actual)

Study Completion Date

August 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Dana-Farber Cancer Institute, Brigham and Women's Hospital, Genentech, Inc.

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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 Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

B-cell Lymphoma, Indolent B-cell Lymphoma

Keywords

rituximab

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

40 (Actual)

8. Arms, Groups, and Interventions

Arm Title

rituximab

Arm Type

Other

Arm Description

single-arm, open-label, interventional

Intervention Type

Drug

Intervention Name(s)

rituximab

Other Intervention Name(s)

Rituxan

Intervention Description

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).

Primary Outcome Measure Information:

Title

Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas

Description

Time Frame

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

Secondary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

Time Frame

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

Title

Progression-free Survival (PFS)

Description

Time Frame

5 years

Title

Incidence of Severity of Infusion Reactions, Infections and Neutropenia

Description

Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening

Time Frame

24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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 18 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 Exclusion Criteria: 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeremy Abramson, MD

Organizational Affiliation

Massachusetts General Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Massachusetts General Hospital

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

Facility Name

Dana-Farber Cancer Institute

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

12. IPD Sharing Statement

Learn more about this trial

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

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