Lymphoma
Conditions
Keywords
recurrent grade 1 follicular lymphoma, recurrent grade 2 follicular lymphoma, recurrent grade 3 follicular lymphoma
Brief summary
Monoclonal antibodies, such as rituximab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Biological therapies, such as lenalidomide, may stimulate the immune system in different ways and stop cancer cells from growing. Lenalidomide may also stop the growth of non-Hodgkin's lymphoma by blocking blood flow to the cancer. Giving rituximab together with lenalidomide may kill more cancer cells. This randomized phase II trial is studying how well rituximab and/or lenalidomide work in treating patients with follicular non-Hodgkin's lymphoma that is not refractory to rituximab.
Detailed description
Outline: This is a randomized, multicenter study. Patients are randomized to 1 of 3 treatment arms. Please see the Arms section for a description of each treatment arm. The primary and secondary objectives of the study are provided below. Primary Objectives: * To determine the response rate (overall and complete) after lenalidomide therapy and rituximab + lenalidomide in follicular NHL patients who have relapsed. * To determine time to progression after lenalidomide therapy and rituximab and lenalidomide in follicular NHL patients who have relapsed. Secondary Objectives: * To compare the time to progression of the previous rituximab regimen to that obtained subsequently to lenalidomide therapy and rituximab + lenalidomide. * To determine the toxicity profile of lenalidomide therapy and of rituximab and lenalidomide in follicular NHL patients who have received a previous rituximab regimen. * To correlate Fc receptor polymorphism profiling with response to lenalidomide or rituximab + lenalidomide in previously treated patients with follicular NHL who have relapsed. * To evaluate changes in Natural Killer (NK) cells, activated NK cells, activated T-cells and several plasma cytokines followed by rituximab therapy and correlation of observed changes to objective response rates. After completion of study treatment, patients are followed for up to 10 years from study entry.
Interventions
BIOLOGICALrituximab
Given IV
DRUGlenalidomide
Given orally
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Documentation of Disease * Previously treated, histologically confirmed follicle center cell lymphoma, World Health Organization (WHO) classification, grade 1, 2, or 3a * Institutional flow cytometry or immunohistochemistry must confirm Cluster of Differentiation 20 (CD20) antigen expression. * Prior Treatment * Patient must have been treated with rituximab either alone or in combination with chemotherapy. * Patient must have a time to progression of ≥ 6 months from last rituximab dose. * No corticosteroids within two weeks prior to study, except for maintenance therapy for a non-malignant disease. Maintenance therapy dose may not exceed 20 mg/day prednisone or equivalent. * No prior radioimmunotherapy within 12 months of study entry. * Age ≥ 18 years. * Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2. * Measurable disease must be present either on physical examination or imaging studies. Non-measurable disease alone is not acceptable. Any tumor mass \>1 cm is acceptable.Lesions that are considered non-measurable include the following: * Bone lesions * Ascites * Pleural/pericardial effusion * Lymphangitis cutis/pulmonis * Bone marrow * No known Central Nervous System (CNS) involvement by lymphoma. * No known Human Immunodeficiency Virus (HIV) infection. * Non-pregnant and non-nursing. * Patients with a currently active second malignancy, other than non-melanoma skin cancers, are not eligible. * Patients with a recent history (within 3 months of study entry) of Deep Vein Thrombosis/Pulmonary Embolism (DVT/PE) are not eligible. * Required Initial Laboratory Values: * Absolute Neutrophil Count (ANC) ≥ 1000/µL * Platelet count ≥ 75,000/µL * Creatinine \< 1.5 x Upper Limit of Normal (ULN) unless attributed to lymphoma or calculated clearance \> 50 mL/min (patients on dialysis are not eligible) * Total Bilirubin ≤ 2 x ULN unless attributed to lymphoma or Gilbert's disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | Duration of treatment (12 cycles) | Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a \>/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease. |
| Time to Progression | Up to 10 years | Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method. |
Countries
United States
Participant flow
Recruitment details
Between October 2006 and April 2011, 97 participants were accrued to the study.
Pre-assignment details
Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.
Participants by arm
| Arm | Count |
|---|---|
| Arm I - Rituximab Patients receive rituximab 375 mg/m\^2 IV on days 1, 8, 15, and 22. | 0 |
| Arm II - Lenalidomide Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12. Treatment repeats every 28 days. | 45 |
| Arm III - Lenalidomide and Rituximab Patients receive oral lenalidomide 15 mg once daily on days 1-21 in cycle 1, then 20 mg once daily on days 1-21 cycle 2-12 Patients also receive rituximab 375 mg/m\^2 IV on days 8, 15, 22 and 29. | 46 |
| Total | 91 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 3 | 0 |
Baseline characteristics
| Characteristic | Arm II - Lenalidomide | Total | Arm III - Lenalidomide and Rituximab |
|---|---|---|---|
| Age, Continuous | 63 years | 63 years | 64 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 1 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 4 Participants | 4 Participants | 0 Participants |
| Race (NIH/OMB) White | 37 Participants | 81 Participants | 44 Participants |
| Region of Enrollment United States | 45 participants | 91 participants | 46 participants |
| Sex: Female, Male Female | 18 Participants | 37 Participants | 19 Participants |
| Sex: Female, Male Male | 27 Participants | 54 Participants | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 44 / 45 | 41 / 45 |
| serious Total, serious adverse events | 0 / 0 | 8 / 45 | 12 / 45 |
Outcome results
Primary
Overall Response Rate
Response is assessed by investigator according to International Working Group (IWG) criteria. A complete response requires disappearance of all evidence of disease. A partial response is a \>/= 50% decrease in the sum of products of 6 largest dominant nodes or nodal masses as well as for splenic and hepatic nodules. No increase in size of nodes, liver or spleen and no new sites of disease.
Time frame: Duration of treatment (12 cycles)
Population: Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm II - Lenalidomide | Overall Response Rate | 53.3 percentage of participants |
| Arm III - Lenalidomide and Rituximab | Overall Response Rate | 76.1 percentage of participants |
p-value: 0.29Fisher Exact
Primary
Time to Progression
Time to progression (TTP) is defined as the time from study entry until progression or death without progression. The median TTP with 95% CI was estimated using the Kaplan-Meier method.
Time frame: Up to 10 years
Population: Three participants assigned to the lenalidomide arm alone arm never began treatment, and the rituximab arm was discontinued early.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm II - Lenalidomide | Time to Progression | 1.1 years |
| Arm III - Lenalidomide and Rituximab | Time to Progression | 2 years |
p-value: 0.002Log Rank