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

Phase 2TerminatedNCT00632827

University of California, San Francisco21 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Peripheral T-Cell Lymphoma

Interventions

GemcitabineDRUG

Chemotherapy medication used to treat a number of types of cancer

NavelbineDRUG

Navelbine is an chemotherapy medication used to treat a number of types of cancer

Doxorubicin Hydrochloride Liposome InjectionDRUG

Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

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

Locations (1)

Washington University

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Progression Free Survival

Progression-Free Survival will be defined the percentage of participants alive and progression-free at median follow up of 25 months. Patients will be routinely followed for disease progression and those who die without a reported prior progression will be considered to have progressed on the day of their death. Patients who did not progress or die will be censored at the day of their last treatment assessment. Patients who have not received study regimen or did not have on-study treatment assessments will be censored on the day they entered the trial. Patients who receive chemotherapy for reasons other than documented progression of disease or clinical progression without documented progression will be censored on the earliest date of subsequent therapy

Time frame: Up to 3 years

Secondary Outcomes

Overall Survival Rate

Overall Survival will be defined the percentage of participants alive at median follow up of 25 months. If the patient is lost to follow-up, survival will be censored on the last date the patient was known to be alive. The analysis is expected to occur up to 60 months after the first patient is entered the trial.

Time frame: Up to 5 years

Complete Response Rate

The complete response rate will be defined as the total number of patients who have defined complete response using study regimen (intensive induction therapy/progressive chemotherapy/stem cell rescue), divided by the number of patients entered in the trial using response-evaluable patients.

Time frame: Up to 3 years

Median Time to Response

The time to response is measured from the time measurement criteria are met for complete response or partial response (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started) in months.

Time frame: Up to 2 years

Data from ClinicalTrials.gov

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