A Phase 2 interventional study of denileukin diftitox and rituximab in Lymphoma, sponsored by Alliance for Clinical Trials in Oncology. Completed at 165 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2017-04-18.
Sponsored by Alliance for Clinical Trials in Oncology · Phase 2, Interventional, and Treatment
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.
OBJECTIVES:
Primary
Secondary
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.
5,578 studies on the registry are indexed under Lymphoma; 825 are open to participants now.
This study's enrollment of 24 is below the median of 40 across 4,508 interventional studies indexed under Lymphoma.
Browse Lymphoma studies →Alliance for Clinical Trials in Oncology is the lead sponsor of 499 studies on the registry; 27 are open to participants now.
Of its 6 completed or terminated interventional studies of FDA-regulated products, 6 (100%) have results posted.
Counted across the registry records on this site, refreshed daily.
DISEASE CHARACTERISTICS:
Pathologically confirmed follicular B-cell non-Hodgkin's lymphoma (NHL)
Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques
PATIENT CHARACTERISTICS:
PRIOR CONCURRENT THERAPY:
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.
Biological: denileukin diftitox · Biological: rituximab
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
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
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
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
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
| Milestone | Rituximab + Denileukin Diftitox |
|---|---|
| Started | 24 |
| Completed | 23 |
| Not completed | 1 |
| Withdrew: Death | 1 |
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.
| proportion of participants | Rituximab + Denileukin Diftitox |
|---|---|
| Proportion of Confirmed Tumor Response (Complete Response [CR], Unconfirmed CR, and Partial Response) | 0.48 (0.27 to 0.69) |
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.
| Measure | Rituximab + Denileukin Diftitox |
|---|---|
| Survival Time | NA (NA to NA) |
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.
| Measure | Rituximab + Denileukin Diftitox |
|---|---|
| Time to Disease Progression | NA (NA to NA) |
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.
| months | Rituximab + Denileukin Diftitox |
|---|---|
| Duration of Response | 22.5 (7.3 to 22.5) |
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.
| months | Rituximab + Denileukin Diftitox |
|---|---|
| Time to Subsequent Therapy | NA (8.5 to NA) |
Collected over Adverse events are assessed during Treatment (weekly while receiving treatment and prior to the start of a new cycle) and during Observation (1 month after completing treatment, at 4, 7, and 10 months after completing treatment, 1 year after treatment, and every 6 months for years 2-5); up to 5 years.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Rituximab + Denileukin Diftitox | — | 7/23 (30.4%) | 22/23 (95.7%) |
| Event | Rituximab + Denileukin Diftitox |
|---|---|
| Capillary leak syndromeVascular disorders | 5/23 |
| FatigueGeneral disorders | 2/23 |
| Creatine phosphokinase increasedInvestigations | 2/23 |
| Cardiac valve diseaseCardiac disorders | 1/23 |
| Left ventricular dysfunctionCardiac disorders | 1/23 |
| Myocardial ischemiaCardiac disorders | 1/23 |
| Premature ventricular contractionsCardiac disorders | 1/23 |
| Ventricular bigeminyCardiac disorders | 1/23 |
| Abdominal painGastrointestinal disorders | 1/23 |
| ConstipationGastrointestinal disorders | 1/23 |
| Event | Rituximab + Denileukin Diftitox |
|---|---|
| Hemoglobin decreasedBlood and lymphatic system disorders | 11/23 |
| Serum albumin decreasedMetabolism and nutrition disorders | 9/23 |
| Platelet count decreasedInvestigations | 7/23 |
| HypersensitivityImmune system disorders | 6/23 |
| Alanine aminotransferase increasedInvestigations | 6/23 |
| Aspartate aminotransferase increasedInvestigations | 6/23 |
| Lymphocyte count decreasedInvestigations | 4/23 |
| Blood glucose increasedMetabolism and nutrition disorders | 4/23 |
| ChillsGeneral disorders | 3/23 |
| FatigueGeneral disorders | 3/23 |
| Age, Continuous(years) | Rituximab + Denileukin Diftitox |
|---|---|
| Median | 60.0 (27.0 to 79.0) |
| Sex: Female, Male(Participants) | Rituximab + Denileukin Diftitox |
|---|---|
| Female | 11 |
| Male | 12 |
| Region of Enrollment(participants) | Rituximab + Denileukin Diftitox |
|---|---|
| United States | 23 |
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