B-cell Lymphoma, Indolent B-cell Lymphoma
Conditions
Keywords
rituximab
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.
Interventions
DRUGrituximab
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).
Sponsors
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Genentech, Inc.
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas | after a median number of 8 maintenance cycles, up to 24 weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate (ORR) | after a median number of 8 maintenance cycles, up to 24 weeks | 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) | 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 | 24 months | Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab single-arm, open-label, interventional
rituximab: 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). | 40 |
| Total | 40 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
| Overall Study | reason unknown | 2 |
Baseline characteristics
| Characteristic | Rituximab |
|---|---|
| Age, Continuous | 60 years |
| elevated LDH (Lactate dehydrogenase) | 11 Participants |
| Follicular lymphoma prognostic index (FLIPI) FLIPI score not available | 2 Participants |
| Follicular lymphoma prognostic index (FLIPI) High risk | 17 Participants |
| Follicular lymphoma prognostic index (FLIPI) Intermediate risk | 15 Participants |
| Follicular lymphoma prognostic index (FLIPI) Low risk | 6 Participants |
| Hgb<12 g/dL | 9 Participants |
| Involvement of >4 nodal sites | 17 Participants |
| Lymphoma type Follicular | 31 Participants |
| Lymphoma type Indolent B cell, not otherwise specified | 2 Participants |
| Lymphoma type Marginal zone | 4 Participants |
| Lymphoma type Small lymphocytic | 3 Participants |
| Region of Enrollment United States | 40 participants |
| Sex: Female, Male Female | 27 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 40 / 40 |
| serious Total, serious adverse events | 4 / 40 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab | Determine Complete Response Rate (CRR) of Increased Dose Rituximab in Indolent B-cell Lymphomas | 21 Participants |
Secondary
Incidence of Severity of Infusion Reactions, Infections and Neutropenia
Toxicity grades: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening
Time frame: 24 months
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Rituximab | Incidence of Severity of Infusion Reactions, Infections and Neutropenia | Grade 3/4 neutropenia | 3 Participants |
| Rituximab | Incidence of Severity of Infusion Reactions, Infections and Neutropenia | Any allergic reactions with infusions | 19 Participants |
| Rituximab | Incidence of Severity of Infusion Reactions, Infections and Neutropenia | Grade 3 allergic reactions with infusions | 2 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab | Overall Response Rate (ORR) | 32 Participants |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Rituximab | Progression-free Survival (PFS) | 19 Participants |