Treatment of Peripheral T-Cell Lymphoma With Aggressive Induction Chemotherapy Followed by Autologous Stem Cell Transplant Using Denileukin Diftitox (Ontak)

This study is currently recruiting participants.

Verified by University of California, San Francisco, February 2009

First Received: February 28, 2008 Last Updated: February 17, 2009 History of Changes

Sponsors and Collaborators:	University of California, San Francisco Eisai Limited Washington University School of Medicine Wake Forest University University of Chicago University of North Carolina Roswell Park Cancer Institute Weill Medical College of Cornell University
Information provided by:	University of California, San Francisco
ClinicalTrials.gov Identifier:	NCT00632827

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 II

Study Type:	Interventional
Study Design:	Treatment, Open Label, Single Group Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Lymphoma

Drug Information available for: Denileukin diftitox

U.S. FDA Resources

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 ]

Estimated Enrollment:	45
Study Start Date:	June 2008
Estimated Study Completion Date:	June 2012
Estimated Primary Completion Date:	June 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Treatment A: Experimental Gemcitabine/Navelbine/Doxil Days 1 and 8 G-CSF Days 4-6 and 10-15	Drug: REGIMEN Induction chemotherapy
Treatment B: Experimental 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

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

Contacts

Contact: Beth Davis, C.C.R.A.	415.502.3176	bdavis@medicine.ucsf.edu
Contact: Natalie Jeha, M.A.	415.476.4126	njeha@medicine.ucsf.edu

Locations

United States, California
University of California San Francisco	Recruiting
San Francisco, California, United States, 94143
Contact: Beth Davis, C.C.R.A. 415-502-3176 bdavis@medicine.ucsf.edu
Contact: Natalie Jeha, M.A. 415.476.4126 njeha@medicine.ucsf.edu
Principal Investigator: Lawrence Kaplan, M.D.
Sub-Investigator: Charles Linker, M.D.
Sub-Investigator: Lloyd Damon, M.D.
Sub-Investigator: Jeffrey Wolf, M.D.
Sub-Investigator: Wei Ai, M.D.
Sub-Investigator: Karin Gaensler, M.D.
Sub-Investigator: Kristen Hege, M.D.
Sub-Investigator: Peter Sayre, M.D.
Sub-Investigator: Caroline Behler, M.D.
United States, Missouri
Washington University	Recruiting
St. Louis, Missouri, United States, 63110
Contact: Justina First 314-362-4206 jfirst@dom.wustl.edu
Principal Investigator: Nancy Barlett, M.D.
United States, New York
Weill Cornell Medical College	Recruiting
New York, New York, United States, 10021
Contact: Sara Marcus 212-746-1493 sam2020@med.cornell.edu
Principal Investigator: Rebecca Elstrom, M.D.
United States, North Carolina
Wake Forest University Health Sciences	Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Jennifer H. Black, BS, CCRP 336-806-7882 jhblack@wfubmc.edu
Principal Investigator: David Hurd, M.D.

Sponsors and Collaborators

University of California, San Francisco

Eisai Limited

Washington University School of Medicine

Wake Forest University

University of Chicago

University of North Carolina

Roswell Park Cancer Institute

Weill Medical College of Cornell University

More Information

Additional Information:

UCSF Cancer Center This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	University of California San Francisco ( Lawrence Kaplan, M.D. and Charles Linker, M.D. )
Study ID Numbers:	UC-PTCL-ONTAK
Study First Received:	February 28, 2008
Last Updated:	February 17, 2009
ClinicalTrials.gov Identifier:	NCT00632827 History of Changes
Health Authority:	United States: Food and Drug Administration

Study placed in the following topic categories:

Lymphatic Diseases
Peripheral T-cell Lymphoma
Immunoproliferative Disorders
Denileukin diftitox
Lymphoma, T-Cell

Lymphoma, Non-Hodgkin
Lymphoproliferative Disorders
Aggression
Lymphoma, T-Cell, Peripheral
Lymphoma

Additional relevant MeSH terms:

Neoplasms by Histologic Type
Immunoproliferative Disorders
Immune System Diseases
Antineoplastic Agents
Lymphoma, T-Cell, Peripheral
Pharmacologic Actions
Lymphatic Diseases

Neoplasms
Lymphoma, T-Cell
Denileukin diftitox
Therapeutic Uses
Lymphoproliferative Disorders
Lymphoma, Non-Hodgkin
Lymphoma

ClinicalTrials.gov processed this record on September 10, 2009