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Lymphoma, T-Cell, PeripheralPhase 2NCT00211185

A Study of ONTAK and CHOP in Newly Diagnosed, Peripheral T-Cell Lymphoma

A Phase 2 study testing Denileukin diftitox, Cyclophosphamide and Doxorubicin in people with Lymphoma, T-Cell, Peripheral, run by Eisai Inc. at 49 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Lymphoma, T-Cell, Peripheral
What is being tested?
Denileukin diftitox, Cyclophosphamide and Doxorubicin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
49 participants
Where
49 sitesUnited States
Study dates
14 Mar 2004to 23 Dec 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.
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  • 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.

Who cannot join

  • 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%.
Show all 12Show fewer
  • 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.

Trial locations and contacts

49 sites in 1 country.

49 sites in 1 country

United States49 sites

  • New York Oncology Hematology, P.C.

    Albany, New York, 12208

  • Texas Cancer Center

    Arlington, Texas, 76014

  • Marnie McFaddin Ward Cancer Center

    Beaumont, Texas, 77702-1449

  • Texas Oncology,P.A.

    Bedford, Texas, 76022

  • Birmingham Hematology and Oncology

    Birmingham, Alabama, 35205

  • Dana Farber/ Harvard Cancer Center

    Boston, Massachusetts, 02115

  • New England Medical Center

    Boston, Massachusetts

  • Raleigh Hematology Oncology Associates

    Cary, North Carolina, 27511

  • Hematology Oncology Associates of IL

    Chicago, Illinois, 60611

  • Robert H. Lurie Comprehensive Cancer Center

    Chicago, Illinois, 60611

  • Rush University Medical Center

    Chicago, Illinois, 60612

  • Barrett Cancer Center-University of Cincinnati

    Cincinnati, Ohio, 45206

  • Missouri Cancer Associates

    Columbia, Missouri, 65201

  • Texas Cancer Center at Medical City

    Dallas, Texas, 75230-2510

  • The Texas Cancer Center

    Dallas, Texas, 75237

  • Rocky Mountain Cancer Center

    Denver, Colorado, 80218

  • Puget Sound Cancer Center

    Edmonds, Washington, 98026

  • El Paso Cancer Treatment Center

    El Paso, Texas, 79915

  • Texas Oncology

    Fort Worth, Texas, 76104

  • Texas Oncology

    Garland, Texas, 75042-5788

  • Cancer Centers of the Carolinas

    Greenville, South Carolina, 29605

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Kansas City Cancer Centers

    Kansas City, Missouri, 64111

  • Greater Dayton Cancer Center

    Kettering, Ohio, 45409

  • Kansas City Cancer Centers

    Lenexa, Kansas, 66214

  • Longview Cancer Center

    Longview, Texas, 75601

  • Allison Cancer Center

    Midland, Texas, 79701-5946

  • Minnesota Oncology Hematology, P.A.

    Minneapolis, Minnesota, 55404

  • Hematology Oncology Associates of NNJ

    Morristown, New Jersey, 07960

  • Yale University School of Medicine

    New Haven, Connecticut, 06250

  • Cancer Care & Hematology Specialists of Chicagoland

    Niles, Illinois, 60714

  • Virginia Oncology Associates

    Norfolk, Virginia, 23502

  • Ocala Oncology Center

    Ocala, Florida, 34474

  • Cancer Centers of Florida, P.A.

    Ocoee, Florida, 34761

  • West Texas Cancer Center

    Odessa, Texas, 79761

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111-2497

  • Hematology Oncology Associates

    Phoenix, Arizona, 85012

  • St. Joseph Oncology Inc.

    Saint Joseph, Missouri, 64507

  • Oncology and Hematology Associates of SW VA Inc.

    Salem, Virginia, 24153

  • HOAST Medical Dr.

    San Antonio, Texas, 78229

  • New Mexico Cancer Care Associates

    Santa Fe, New Mexico, 87505

  • Siouxland Hematology Oncology

    Sioux City, Iowa, 51101

  • Cancer Care Northwest

    Spokane, Washington, 99218

  • Arch Medical Services

    St Louis, Missouri, 63141

  • Stanford Cancer Center

    Stanford, California, 94305-5826

  • Tyler Cancer Center

    Tyler, Texas, 75702

  • Northwest Cancer Specialists

    Vancouver, Washington, 98684

  • Waco Cancer Care and Research Center

    Waco, Texas, 76712

  • Yakima Valley Memorial Hospital/North Star Lodge

    Yakima, Washington, 98902

Other trials in United States

About this study

Official title: A Pilot Phase II Study to Determine the Safety and Efficacy of the Combination of ONTAK With CHOP in Peripheral T-Cell Lymphoma.

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.

Being tested
Denileukin diftitox, Cyclophosphamide, Doxorubicin, Vincristine, Prednisone
Medical subject headings
Lymphoma, T-Cell, Peripheral

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Denileukin diftitoxDrug

    Also called ONTAK, DAB389 IL-2

    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.

  • CyclophosphamideDrug

    Also called CHOP

    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.

  • DoxorubicinDrug

    Also called CHOP

    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.

  • VincristineDrug

    Also called CHOP

    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.

  • PrednisoneDrug

    Also called CHOP

    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.

  • PegfilgrastimOther

    Also called Neulasta, granulocyte-colony stimulating factor, G-CSF

    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.

Study groups in NCT00211185
Study groupRoleWhat they receive
Denileukin diftitox in combination with CHOPExperimentalUnblinded 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.
Receives: Drug: Denileukin diftitox; Drug: Cyclophosphamide; Drug: Doxorubicin; Drug: Vincristine; Drug: Prednisone; Other: Pegfilgrastim

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 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

  2. 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.

    Measured: 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

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

Secondary outcomes (5)

  1. 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.

    Measured: From the start of the treatment to the date of participant's death assessed up to 5 years 9 months

  2. 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.

    Measured: From the start of the treatment to the date of the participant's death assessed up to 5 years 9 months

  3. 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.

    Measured: 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

  4. 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.

    Measured: 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

  5. 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.

    Measured: From date of randomization until death, or administrative close of study, whichever came first, assessed up to 5 years 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Sep 2005 (estimated)
  2. Study start14 Mar 2004
  3. Primary completionAug 2008
  4. Study completion23 Dec 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
49 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00211185
Sponsor's protocol ID
#35
Status last verified
Mar 2020
First submitted
13 Sep 2005
Last updated
18 Mar 2020
Data monitoring committee
Yes

Publications

  • Francine M. Foss, Nelida Sjak-Shie, Andre Goy, Ranjana Advani, Eric Jacobsen, and Mark Acosta A Phase II Study of Denileukin Diftitox (Ontak®) with CHOP Chemotherapy in Patients with Newly-Diagnosed Aggressive T-Cell Lymphomas, the CONCEPT Trial: Interim Analysis. Blood (ASH Annual Meeting Abstracts), Nov 2006; 108: 2461.

  • Foss FM, Sjak-Shie N, Goy A, Jacobsen E, Advani R, Smith MR, Komrokji R, Pendergrass K, Bolejack V. A multicenter phase II trial to determine the safety and efficacy of combination therapy with denileukin diftitox and cyclophosphamide, doxorubicin, vincristine and prednisone in untreated peripheral T-cell lymphoma: the CONCEPT study. Leuk Lymphoma. 2013 Jul;54(7):1373-9. doi: 10.3109/10428194.2012.742521. Epub 2013 Jan 29.

    PubMed 23278639

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Denileukin diftitox, Cyclophosphamide and Doxorubicin in people with Lymphoma, T-Cell, Peripheral, run by Eisai Inc. at 49 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 18 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 49 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 18 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Summary of All Adverse Events by Frequency in Greater Than 20% of Treated Participants (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). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00211185, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Mar 2020.

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