Clinical trial NCT00632827: Treatment of PTCL With Aggressive Induction Therapy Followed by Autologous SCT Using Denileukin Diftitox (Ontak)
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Peripheral T-Cell Lymphoma
Lead sponsor: University of California, San Francisco
Sponsor class: OTHER
Collaborators: name: Eisai Inc.
name: Washington University School of Medicine
First posted: 2008-03-11
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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 gemcitabine, vinorelbine, Doxil (GND) will be used followed by two cycles of augmented dose Cyclophosphamide (CHOP) plus high-dose methotrexate (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 HiDAC/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 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 (AILT) (IPI \>2)
  * Non-primary cutaneous Alk-1-negative anaplastic large cell lymphoma
  * Extranodal natural killer (NK)/T lymphoma (Excluding stage I/II nasal disease)
  * Blastic NK cell lymphoma
  * Enteropathy type T-cell lymphoma
  * Cutaneous 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, aspartate aminotransferase (AST) \< 3x upper limit of normal
* Patients who test positive for Hepatitis B surface Ag (HepBSAg) or Hepatitis C antibody (HepCAb) are eligible provided all of the following criteria are met:

  * bilirubin ≤ 2 x upper limit of normal;
  * aspartate aminotransferase (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 lamivudine (3TC) or investigator's preferred antiviral regimen throughout protocol therapy and for 6-12 months thereafter.

* Neutrophils ≥ 1000/microlitre (uL) platelets \> 100,000/uL
* HIV-negative
* Left ventricular ejection fraction (LVEF) of ≥ 45%
* 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 inImmunoglobulin M (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
* Adult T-cell leukemia/lymphoma

Primary outcomes:
measure: Progression Free Survival
timeFrame: Up to 3 years
Secondary outcomes:
measure: Overall Survival Rate
timeFrame: Up to 5 years
measure: Complete Response Rate
timeFrame: Up to 3 years
measure: Median Time to Response
timeFrame: Up to 2 years
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
Study officials:
affiliation: University of California, San Francisco
name: Lawrence Kaplan, MD
role: PRINCIPAL_INVESTIGATOR
References: