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Treatment of PTCL With Aggressive Induction Therapy Followed by Autologous SCT Using Denileukin Diftitox (Ontak)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Esai Pharmaceuticals
Washington University Early Recognition Center
Wake Forest School of Medicine
University of Chicago
University of North Carolina
Roswell Park Cancer Institute
Weill Medical College of Cornell University
Information provided by (Responsible Party):
Lawrence Kaplan, University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00632827
First received: February 28, 2008
Last updated: October 3, 2014
Last verified: October 2014
  Purpose

This study examines the use of denileukin diftitox (Ontak) for patients with peripheral T-cell lymphoma who are candidates for autologous stem cell transplants.


Condition Intervention Phase
Peripheral T-Cell Lymphoma
Drug: REGIMEN
Drug: REGIMEN B
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Treatment of Peripheral T-cell Lymphoma With Aggressive Induction Chemotherapy Followed by Autologous Stem Cell Transplant Using Denileukin Diftitox (Ontak) for In-vivo Purging and Post-Transplant Therapy: A Multicenter Phase II Clinical Trial

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • The primary endpoint of this trial is improvement in 3-year progression-free survival from 30% to 50% under the study regimen. [ Time Frame: 3 years ] [ Designated as safety issue: No ]

Enrollment: 21
Study Start Date: June 2008
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment A
Gemcitabine/Navelbine/Doxil Days 1 and 8 G-CSF Days 4-6 and 10-15
Drug: REGIMEN
Induction chemotherapy
Experimental: Treatment B
Cyclophosphamide/Doxorubicin/Vincristine on Day 1 Prednisone Days 1-5 Methotrexate Day 15
Drug: REGIMEN B
Induction Chemotherapy

Detailed Description:

This protocol proposes first to increase the proportion of patients who achieve adequate initial disease control and are able to proceed to autologous stem cell transplant (ASCT) in first complete or partial remission. It administers intensive and novel induction therapy.

Two cycles of GND (gemcitabine, vinorelbine, Doxil) will be used followed by two cycles of augmented dose CHOP (Cyclophosphamide) plus high-dose MTX. Patients will be restaged after two cycles of GND to assess response to GND alone and again after the second cycle of augmented CHOP/high-dose MTX.

Those achieving a remission status will receive intensive consolidation with HDAC/etoposide followed by stem cell mobilization. A five-day course of denileukin diftitox (Ontak) will be administered at and will serve as an in vivo purge. This will be followed by autologous stem cell transplant.

Those not achieving partial remission or better following the four induction courses will receive 2 cycles of denileukin diftitox(Ontak) for 5 days. Those achieving partial remission or better to this regimen will go on to consolidation/mobilization and autologous stem cell transplant.

Post-transplant, denileukin diftitox will also be used as an additional module of therapy.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Histologic diagnosis of any of the following:

    • Peripheral T-cell lymphoma not otherwise specified (PTCL-U),(IPI >2)
    • Angioimmunoblastic T-cell lymphoma (IPI >2)
    • Non-primary cutaneous Alk-1-negative anaplastic large cell lymphoma
    • Extranodal NK/T lymphoma (Excluding stage I/II nasal disease)
    • Blastic NK cell lymphoma
    • Enteropathy type T-cell lymphoma
    • Subcutaneous panniculitis-like T-cell lymphoma
    • Hepatosplenic T-cell lymphoma
  • Measurable or assessable disease is not required.
  • Age >18 and < 70 years
  • Previously untreated or 1 prior cycle of chemotherapy
  • Creatinine < 2.0 mg/dL
  • Total bilirubin < 2.0 mg/dL, AST < 3x upper limit of normal
  • Patients who test positive for HepBSAg or HepC Ab are eligible provided all of the following criteria are met:

    • bilirubin ≤ 2 x upper limit of normal;
    • AST ≤ 3 x upper limit of normal;
    • liver biopsy demonstrates ≤ grade 2 fibrosis and no cirrhosis.

Hepatitis B surface Ag(+) patients will be treated with amivudine (3TC) or investigator's preferred antiviral regimen throughout protocol therapy and for 6-12 months thereafter.

  • Neutrophils >1000/uL platelets > 100,000/uL
  • Albumin > 3.0 mg/dL
  • HIV-negative
  • No known hypersensitivity to denileukin diftitox or any of its components: diptheria toxin, interleukin-2, or excipients
  • Non-pregnant, non-nursing: Treatment under this protocol would expose an unborn child to significant risks. Women and men of reproductive potential should agree to use an effective means of birth control.
  • Patients with a "currently active" second malignancy, other than non-melanoma skin cancers are not eligible. (This includes Waldenstrom's Macroglobulinemia, since such patents have experienced transient increases in IgM following initiation of rituximab, with the potential for hyperviscosity syndrome requiring plasmapheresis). Patients are not considered to have a "currently active" malignancy if they have completed anti-cancer therapy, and are considered by their physician to be at less than 30% risk of relapse.

Exclusion Criteria:

  • PTCL-U / AILT with IPI 0 or 1 Extranodal NK/T nasal stage I/II T-lymphoblastic lymphoma Adult T-cell leukemia/lymphoma
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00632827

Locations
United States, Missouri
Washington University
St. Louis, Missouri, United States, 63110
United States, New York
Weill Cornell Medical College
New York, New York, United States, 10021
United States, North Carolina
Wake Forest University Health Sciences
Winston-Salem, North Carolina, United States, 27157
Sponsors and Collaborators
University of California, San Francisco
Esai Pharmaceuticals
Washington University Early Recognition Center
Wake Forest School of Medicine
University of Chicago
University of North Carolina
Roswell Park Cancer Institute
Weill Medical College of Cornell University
  More Information

Additional Information:
No publications provided

Responsible Party: Lawrence Kaplan, Clinical Professor of Medicine; Director, Adult Lymphoma Program, University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00632827     History of Changes
Other Study ID Numbers: UC-PTCL-ONTAK
Study First Received: February 28, 2008
Last Updated: October 3, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Lymphoma
Lymphoma, T-Cell
Lymphoma, T-Cell, Peripheral
Immune System Diseases
Immunoproliferative Disorders
Lymphatic Diseases
Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Neoplasms
Neoplasms by Histologic Type
Denileukin diftitox
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014