A Study of ONTAK and CHOP in Newly Diagnosed, Peripheral T-Cell Lymphoma
- Conditions
- Lymphoma, T-Cell, Peripheral
- Interventions
- Registration Number
- NCT00211185
- Lead Sponsor
- Eisai Inc.
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 49
- Pathological diagnosis of peripheral T-cell lymphoma of one of the following histologies as per the REAL classification: peripheral T-cell lymphoma (unspecified), anaplastic large cell lymphoma CD30+, angioimmunoblastic T-cell lymphoma, nasal/nasal type T/NK cell lymphoma, intestinal T-cell lymphoma, hepatosplenic T-cell lymphoma, subcutaneous panniculitic T-cell lymphoma.
- Treatment naïve except for prior radiation or a single cycle of CHOP.
- Patients must have at least one clear-cut bidimensionally measurable site by physical exam and/or computed tomography.
- Prior radiation therapy for localized disease is allowed as long as the irradiated area is not at the mediastinal area or at the only site of measurable disease. Therapy must be completed at least 4 weeks before the enrollment in study.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2.
- At least 18 years of age.
- Adequate bone marrow reserve, indicated by absolute neutrophil count (ANC) > or equal to 1000/microL, platelets > or equal to 50,000/microL (25,000/MicroL if thrombocytopenia secondary to bone marrow involvement by lymphoma), and hemoglobin > or equal to 8 g/dL.
- Adequate liver function, indicated by bilirubin < or equal to 1.5 times the upper limit of normal (ULN), alanine transaminase (ALT) < or equal to 2 times the ULN or aspartate transaminase (AST) < or equal to 2.0 times the ULN, and albumin > or equal to 3.0 g/dL.
- Adequate renal function, indicated by serum creatinine < or equal to 2.5 mg/dL.
- Women of childbearing potential and sexually active males agree to use an accepted and effective method of contraception.
- Able to give informed consent.
- Diagnosis of Mycosis Fungoides or Sezary Syndrome.
- Active Hepatitis B or Hepatitis C infection.
- Known HIV infection (HIV testing is not required).
- Patients with active infections requiring specific anti-infective therapy are not eligible until all signs of infections have resolved and any continuing treatment if appropriate is given on an outpatient basis.
- Previous doxorubicin therapy with cumulative dose of >100 mg/m2.
- Left Ventricular Ejection Fraction (LVEF) < 50%.
- Patients who are pregnant or breast-feeding.
- Prior invasive malignancies within past 5 years.
- Allergy to or history of allergy to diphtheria toxin or IL-2.
- Preexisting severe cardiovascular disease (e.g. CHF, Severe CAD, cardiomyopathy, MI within the past 3 months, arrhythmia) requiring ongoing treatment.
- Ongoing antineoplastic chemotherapy, radiation, hormonal (excluding contraceptives) or immunotherapy, or investigational medications within past 30 days.
- Patients with deep vein thrombosis within 3 months.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Denileukin diftitox in combination with CHOP Pegfilgrastim Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles. Denileukin diftitox in combination with CHOP Denileukin diftitox Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles. Denileukin diftitox in combination with CHOP Cyclophosphamide Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles. Denileukin diftitox in combination with CHOP Vincristine Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles. Denileukin diftitox in combination with CHOP Doxorubicin Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles. Denileukin diftitox in combination with CHOP Prednisone Unblinded denileukin diftitox at 18 micrograms/kilogram/day (ug/kg/d) was administered intravenously (IV) on Days 1 and 2 of each 21-day cycle. Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) was administered on Day 3 of each 21-day cycle. On Day 4 of each 21-day cycle, pegfilgrastim (a granulocyte colony-stimulating factor (G-CSF)) was started as a prophylaxis to prevent neutropenia. After completion of two 21-day cycles, participants were evaluated for clinical response. Two 21-day cycles with denileukin and CHOP were repeated followed by response evaluations after each set of two 21-day cycles with intent to treat for 6 cycles, with a maximum of 8 cycles.
- Primary Outcome Measures
Name Time Method Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants 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 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.
Summary of All Treatment-Related Adverse Events by Frequency in Greater Than 10% of Treated Participants 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 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.
Summary of Treatment-Related Adverse Events Greater Than or Equal to Grade 3 by System Organ Class 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 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.
Summary of Study Drug-Related (Possible, Probable, or Definite) Serious Adverse Events 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 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.
- Secondary Outcome Measures
Name Time Method Overall Response in the Intent To Treat (ITT) Population From the start of the treatment to the date of participant's death assessed up to 5 years 9 months 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.
Overall Response in the Efficacy Analyzable (EA) Population From the start of the treatment to the date of the participant's death assessed up to 5 years 9 months 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.
Duration of Response 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 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.
Progression-Free Survival 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 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.
Percentage of Participants With Overall Survival From date of randomization until death, or administrative close of study, whichever came first, assessed up to 5 years 9 months 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.
Trial Locations
- Locations (47)
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
Raleigh Hematology Oncology Associates
🇺🇸Cary, North Carolina, United States
Greater Dayton Cancer Center
🇺🇸Kettering, Ohio, United States
Texas Cancer Center at Medical City
🇺🇸Dallas, Texas, United States
The Texas Cancer Center
🇺🇸Dallas, Texas, United States
Dana Farber/ Harvard Cancer Center
🇺🇸Boston, Massachusetts, United States
Barrett Cancer Center-University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
HOAST Medical Dr.
🇺🇸San Antonio, Texas, United States
Rocky Mountain Cancer Center
🇺🇸Denver, Colorado, United States
Kansas City Cancer Centers
🇺🇸Kansas City, Missouri, United States
Hematology Oncology Associates of NNJ
🇺🇸Morristown, New Jersey, United States
St. Joseph Oncology Inc.
🇺🇸Saint Joseph, Missouri, United States
Waco Cancer Care and Research Center
🇺🇸Waco, Texas, United States
Siouxland Hematology Oncology
🇺🇸Sioux City, Iowa, United States
Birmingham Hematology and Oncology
🇺🇸Birmingham, Alabama, United States
Cancer Centers of Florida, P.A.
🇺🇸Ocoee, Florida, United States
Yale University School of Medicine
🇺🇸New Haven, Connecticut, United States
Texas Oncology,P.A.
🇺🇸Bedford, Texas, United States
Stanford Cancer Center
🇺🇸Stanford, California, United States
New England Medical Center
🇺🇸Boston, Massachusetts, United States
Minnesota Oncology Hematology, P.A.
🇺🇸Minneapolis, Minnesota, United States
Hematology Oncology Associates
🇺🇸Phoenix, Arizona, United States
Ocala Oncology Center
🇺🇸Ocala, Florida, United States
Northwest Cancer Specialists
🇺🇸Vancouver, Washington, United States
Longview Cancer Center
🇺🇸Longview, Texas, United States
West Texas Cancer Center
🇺🇸Odessa, Texas, United States
Fox Chase Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Oncology and Hematology Associates of SW VA Inc.
🇺🇸Salem, Virginia, United States
Cancer Care Northwest
🇺🇸Spokane, Washington, United States
Cancer Care & Hematology Specialists of Chicagoland
🇺🇸Niles, Illinois, United States
Missouri Cancer Associates
🇺🇸Columbia, Missouri, United States
Arch Medical Services
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
New Mexico Cancer Care Associates
🇺🇸Santa Fe, New Mexico, United States
New York Oncology Hematology, P.C.
🇺🇸Albany, New York, United States
Cancer Centers of the Carolinas
🇺🇸Greenville, South Carolina, United States
Marnie McFaddin Ward Cancer Center
🇺🇸Beaumont, Texas, United States
Texas Cancer Center
🇺🇸Arlington, Texas, United States
Allison Cancer Center
🇺🇸Midland, Texas, United States
El Paso Cancer Treatment Center
🇺🇸El Paso, Texas, United States
Texas Oncology
🇺🇸Garland, Texas, United States
Tyler Cancer Center
🇺🇸Tyler, Texas, United States
Puget Sound Cancer Center
🇺🇸Edmonds, Washington, United States
Virginia Oncology Associates
🇺🇸Norfolk, Virginia, United States
Yakima Valley Memorial Hospital/North Star Lodge
🇺🇸Yakima, Washington, United States