Study of ONTAK and CHOP (chemotherapy drugs) to find out their ability to make Peripheral T-cell lymphoma disappear (for any period of time) and potentially lengthen life. The study will also compare what kind of side effects these drugs cause and how often they occur. The hypothesis is that patients with newly diagnosed peripheral T-Cell lymphoma, when given ONTAK + CHOP, will tolerate the treatment and will have a 20% improvement in response rate when compared to CHOP alone.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
49
Denileukin diftitox will be administered intravenously (IV) at a dosage of 18 micrograms/kilogram/day (ug/kg/d) on Days 1 and 2 of each 21-Day cycle for a total of 6 cycles, with a maximum of 8 cycles.
Cyclophosphamide will be administered IV at a dosage of 750 milligrams/meter squared (mg/m\^2) on Day 3 of each 21-day cycle for 6 cycles, with a maximum of 8 cycles.
Doxorubicin will be administered IV at a dosage of 50 mg/m\^2 on Day 3 of each 21-day cycle for 6 cycles, with a maximum of 8 cycles.
Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants
An adverse event (AE) was any medical occurrence in a participant who was administered denileukin diftitox and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), and did not necessarily have a causal relationship with this treatment. An AE included any side effect, injury, toxicity, sensitivity reaction, or any undesirable clinical or laboratory event that was not normally observed in the participant. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.
Time frame: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants
A treatment-related adverse event was any medical occurrence in a participant who was administered denileukin diftitox and CHOP and was determined to be possibly, probably, or definitely related to study treatment. An AE included any side effect, injury, toxicity, sensitivity reaction, or any undesirable clinical or laboratory event that was not normally observed in the participant. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.
Time frame: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months
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Vincristine will be administered IV at a dosage of 1.4 mg/m\^2 on Day 3 of each 21-day cycle for 6 cycles, with a maximum of 8 cycles.
Prednisone will be administered orally at a dosage of 100 mg on Days 3 to 7 of each 21-day cycle for 6 cycles, with a maximum of 8 cycles.
Pegfilgrastim will be administered at a dosage of 6 mg subcutaneously on Day 4 to help prevent neutropenia. Alternatively, participants received filgrastim 5 ug/kg/d starting on Day 4 and continued until absolute neutrophil count (ANC) was less than 5000/millimeter squared (mm\^2) for 2 days post-nadir.
Birmingham Hematology and Oncology
Birmingham, Alabama, United States
Hematology Oncology Associates
Phoenix, Arizona, United States
Stanford Cancer Center
Stanford, California, United States
Rocky Mountain Cancer Center
Denver, Colorado, United States
Yale University School of Medicine
New Haven, Connecticut, United States
Ocala Oncology Center
Ocala, Florida, United States
Cancer Centers of Florida, P.A.
Ocoee, Florida, United States
Hematology Oncology Associates of IL
Chicago, Illinois, United States
Robert H. Lurie Comprehensive Cancer Center
Chicago, Illinois, United States
Rush University Medical Center
Chicago, Illinois, United States
...and 39 more locations
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class
Treatment-related AEs were medical occurrences determined to be possibly, probably, or definitely related to study treatment. Severity grading of the AE was according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) severity scale (grades 1 - 5) with grade 3 representing a severe AE. Safety was assessed for all participants who received at least one dose of study medication and was monitored throughout the study. Safety evaluations were based on the incidence, intensity, and type of AE, and clinically significant changes in the participant's medical history, physical examination findings, vital signs, and clinical laboratory results. Participants also notified the study staff of any problems that occurred between visits by telephone, and if necessary, were evaluated by the investigator or study staff at an unscheduled interim visit.
Time frame: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events
A serious adverse event (SAE) was any AE that occurred at any dose and resulted in any of the following outcomes: death, a life-threatening adverse drug experience, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant disability/incapacity, or a congenital anomaly/birth defect. Important medical events that did not result in death, were life-threatening, or required hospitalization were considered a SAE when based upon appropriate medical judgment, jeopardized the participant and required medical or surgical intervention to prevent one of the outcomes listed above. Possibly Related (Poss Rel) applied to AEs judged to be perhaps related to study medication, Probably Related (Prob Rel) applied to AEs judged to have a high degree of certainty as related to study medication, and Definitely Related (Def Rel) related applied to AEs that were judged to be without a doubt related to study medication.
Time frame: From date of first dose up to approximately 4 weeks after discontinuation of denileukin diftitox and CHOP, or after early withdrawal for any reason, up to approximately 5 years 9 months
Overall Response in the Intent To Treat (ITT) Population
Response rate was defined as the percentage of the ITT population who achieved a Complete Response (CR), Unconfirmed Complete Response (CRu), or Partial Response (PR). The International Working Group recommendations on non-Hodgkin's lymphoma response criteria were used to determine response to therapy. Largely, the protocol defined the response criteria as: 1) CR, loss of all detectable clinical and radiographic evidence of disease and disease-related symptoms if present before therapy; 2) CRu, CR with the caveats, response to therapy was accompanied with a 75% reduction in measurable lesion size and/or an indeterminate bone marrow biopsy (if initially positive); and 3) PR, less than or equal to 50% decrease in the sum of the measurements of tumor diameters, no increase in the size of other nodes, liver, or spleen, hepatic or spleen nodules regressed by at least 50%, and/or no new sites of disease.
Time frame: From the start of the treatment to the date of participant's death assessed up to 5 years 9 months
Overall Response in the Efficacy Analyzable (EA) Population
Response rate was defined as the percentage of the EA population who achieved a CR, CRu, or PR. The International Working Group recommendations on non-Hodgkin's lymphoma response criteria were used to determine response to therapy. Largely, the protocol defined the response criteria as: 1) CR, loss of all detectable clinical and radiographic evidence of disease and disease-related symptoms if present before therapy; 2) CRu, CR with the caveats, response to therapy was accompanied with a 75% reduction in measurable lesion size and/or an indeterminate bone marrow biopsy (if initially positive); and 3) PR, less than or equal to 50% decrease in the sum of the measurements of tumor diameters, no increase in the size of other nodes, liver, or spleen, hepatic or spleen nodules regressed by at least 50%, and/or no new sites of disease.
Time frame: From the start of the treatment to the date of the participant's death assessed up to 5 years 9 months
Duration of Response
Duration of response was defined as the length of time from the first date at which the response criteria were met (taking the earliest date at which a PR, CRu, or the confirmed CR occurred) until the date that recurrent or PD or death was accurately documented, per the criteria defined for progression-free survival (PFS). All participants within the EA population who achieved a response per the criteria defined were included in the duration of the response analysis. Participants lost to follow-up prior to PD or death were censored at the date they were last known to still be responding to treatment. Duration of response was estimated using the Kaplan-Meier method with the median duration of response summarized.
Time frame: From the date of the first documented CR (confirmed or unconfirmed) or PR until the date of first documentation of recurrent or PD or death, assessed up to 5 years 9 months
Progression-Free Survival
PFS was defined as the period of time from treatment start to the first documentation of PD, recurrence, or death. PD was defined as a greater than or equal to 50% increase from baseline in the sum of the products of the greatest diameters of any previously identified abnormal node for PRs or non-responders, or the appearance of any new lesions during or at the end of therapy. PFS was censored at the last date for which the response assessment resulted in the absence of PD for participants who did not demonstrate objective progression or recurrence. Participants who withdrew prior to evidence of disease progression or recurrence, PFS was censored at the last date assessment showed an absence of PD.
Time frame: From the date of first dose of study drug until date of first documentation of PD, recurrence, or death from any cause, assessed up to 5 years 9 months
Percentage of Participants With Overall Survival
Overall Survival (OS) was defined as the time from the date of registration to the date of the participant's death. OS was determined by reviewing all participant's records every 6 months until the study was administratively closed or all participants died, whichever occurred first. Participants who were lost to follow-up but were still alive at the date of last contact were censored at the date of last contact. Participants who did not have a recorded date of death were censored for OS at the last date at which they were known to be alive.
Time frame: From date of randomization until death, or administrative close of study, whichever came first, assessed up to 5 years 9 months