Lymphoma
Conditions
Keywords
stage III grade 1 follicular lymphoma, stage III grade 2 follicular lymphoma, stage IV grade 1 follicular lymphoma, stage IV grade 2 follicular lymphoma
Brief summary
RATIONALE: 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. Combinations of biological substances in denileukin diftitox may be able to carry cancer-killing substances directly to cancer cells. Giving rituximab together with denileukin diftitox may kill more cancer cells. PURPOSE: This phase II trial is studying how well giving rituximab together with denileukin diftitox works in treating patients with previously untreated stage III or stage IV follicular B-cell non-Hodgkin's lymphoma.
Detailed description
OBJECTIVES: Primary * Determine the response rate (complete response \[CR\], unconfirmed CR, and partial response) in patients with previously untreated stage III or IV follicular B-cell non-Hodgkin's lymphoma treated with rituximab and denileukin diftitox. * Assess the overall survival, time-to-progression, duration of response, and time-to-new therapy in patients treated with this regimen. Secondary * Determine whether this regimen depletes or inhibits the function of regulatory T cells in these patients. OUTLINE: This is a multicenter study. Patients receive rituximab IV on days 1, 8, 15, and 22. Patients also receive denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. Blood is collected at baseline; on day 1 of courses 2-4; and 1 and 4 months after completion of study treatment for research studies. Research studies include analysis of peripheral blood lymphocyte subsets expressing CD3, CD4, CD8, CD19, CD25, and CD26 by flow cytometry; quantitation of CD4+, CD25+ regulatory T cells by flow cytometry; tumor-specific γ-interferon-secreting T cells by enzyme-linked immunospot assay; tumor-specific cytotoxic T-lymphocyte activity; and immune activation by enzyme-linked immunosorbent assay. After completion of study treatment, patients are followed periodically for up to 5 years after registration. PROJECTED ACCRUAL: A total of 53 patients will be accrued for this study.
Interventions
BIOLOGICALdenileukin diftitox
BIOLOGICALrituximab
Sponsors
National Cancer Institute (NCI)
Alliance for Clinical Trials in Oncology
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
DISEASE CHARACTERISTICS: * Pathologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL) * Stage III or IV disease * Grade 1 or 2 disease * Previously untreated disease * Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques * Clearly defined bidimensional diameter ≥ 2 x 2 cm on physical examination OR \> 2.0 cm in 1 of the dimensions by CT scan, MRI, or plain radiograph imaging * Splenic enlargement may be used as a measurable parameter if the spleen is palpable ≥ 3 cm below the left costal margin * Circulating tumor cells \< 5,000/mm³ * Must have paraffin-embedded tissue blocks/slides available * No CNS lymphoma PATIENT CHARACTERISTICS: * ECOG performance status 0-2 * Life expectancy ≥ 1 year * WBC ≥ 3,400/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 10.0 g/dL * Bilirubin ≤ 1.5 times upper limit of normal (ULN) * Alkaline phosphatase ≤ 3 times ULN * AST ≤ 3 times ULN * Creatinine ≤ 1.5 times ULN * Albumin ≥ 3 g/dL * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 1 year after completion of study therapy * No HIV infection * No other active malignancies * No active uncontrolled infection * No known hypersensitivity to denileukin diftitox or any of its components, including diphtheria toxin, aldesleukin, or excipients PRIOR CONCURRENT THERAPY: * No prior chemotherapy, immunotherapy, vaccines, or radiotherapy for NHL
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response) | Up to 5 years | A confirmed tumor response is defined to be either a CR, CRu or PR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Survival Time | Up to 5 years | Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier. |
| Time to Disease Progression | Up to 5 years | Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier. Progression is defined using the response criteria for non-Hodgkin's lymphoma, as at least a 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or non-responders, or appearance of any new lesion during or at the end of therapy. |
| Duration of Response | Up to 5 years | Duration of response (DOR) is defined as the time from the date at which the patient's objective status is first noted to be either a CR, CRu or PR to the earliest date of progression. The distribution of DOR will be estimated using Kaplan-Meier methods. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease. |
| Time to Subsequent Therapy | Up to 5 years | Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab + Denileukin Diftitox Patients receive 375 mg/m\^2 rituximab IV on days 1, 8, 15, and 22. Patients also receive 18 mcg/kg/day denileukin diftitox IV over 15-60 minutes on days 1-5. Treatment with denileukin diftitox repeats every 21 days for up to 4 courses in the absence of disease progression or unacceptable toxicity. | 23 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 1 |
Baseline characteristics
| Characteristic | Rituximab + Denileukin Diftitox |
|---|---|
| Age, Continuous | 60.0 years |
| Region of Enrollment United States | 23 participants |
| Sex: Female, Male Female | 11 Participants |
| Sex: Female, Male Male | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 23 |
| serious Total, serious adverse events | 7 / 23 |
Outcome results
Primary
Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response)
A confirmed tumor response is defined to be either a CR, CRu or PR. The proportion of successes will be estimated by the number of successes divided by the total number of evaluable patients. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.
Time frame: Up to 5 years
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Rituximab + Denileukin Diftitox | Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response) | 0.48 proportion of participants |
Secondary
Duration of Response
Duration of response (DOR) is defined as the time from the date at which the patient's objective status is first noted to be either a CR, CRu or PR to the earliest date of progression. The distribution of DOR will be estimated using Kaplan-Meier methods. Response criteria for non-Hodgkin's lymphoma (NHL) will be followed. Complete response (CR): (a) Complete disappearance of all detectable disease and disease-related symptoms; (b) All lymph nodes and nodal masses must have regressed to normal size; (c) the spleen must have regressed; CR/unconfirmed (CRu): Those patients who fulfill the criteria in (a) and (c), but with a residual lymph node mass that has regressed by more that 75% in the sum of the products of the greatest diameters (SPD). Partial response (PR): ≥50% decrease in SPD of the six largest dominant nodes or nodal masses; no increase in the size of other nodes, liver, or spleen. Splenic and hepatic nodules must regress by at least 50% in the SPD; No new sites of disease.
Time frame: Up to 5 years
Population: Overall Number of Participants Analyzed reflects only the number of participants with reported data for this outcome.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab + Denileukin Diftitox | Duration of Response | 22.5 months |
Secondary
Survival Time
Survival time is defined as the time from registration to death due to any cause. The distribution of survival time will be estimated using the method of Kaplan-Meier.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab + Denileukin Diftitox | Survival Time | NA |
Secondary
Time to Disease Progression
Time to disease progression is defined as the time from registration to the earliest date of documentation of disease progression. If a patient dies without a documentation of disease progression the patient will be considered to have had tumor progression at the time of their death unless there is sufficient documented evidence to conclude no progression occurred prior to death. The distribution of time to disease progression will be estimated using the method of Kaplan-Meier. Progression is defined using the response criteria for non-Hodgkin's lymphoma, as at least a 50% increase from nadir in the sum of the products of the greatest diameters (SPD) of any previously identified abnormal node for PRs or non-responders, or appearance of any new lesion during or at the end of therapy.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab + Denileukin Diftitox | Time to Disease Progression | NA |
Secondary
Time to Subsequent Therapy
Time to subsequent therapy is defined to be the time from the end of active treatment date to the date subsequent therapy is initiated. The distribution of time to subsequent therapy will be estimated using the method of Kaplan-Meier.
Time frame: Up to 5 years
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Rituximab + Denileukin Diftitox | Time to Subsequent Therapy | NA months |