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

Primary Purpose

Peripheral T-Cell Lymphoma

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Gemcitabine
Navelbine
Doxorubicin Hydrochloride Liposome Injection
Granulocyte-colony stimulating factor (G-CSF)
Pegfilgrastim
Cyclophosphamide
Vincristine
Leucovorin
Methotrexate
Doxorubicin Hydrochloride
Cytarabine
Etoposide
Carmustine
Denileukin diftitox
Sponsored by
University of California, San Francisco
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Peripheral T-Cell Lymphoma

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Washington University

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Treatment Plan

Arm Description

(1) Induction Chemo A; Two 21-day cycles of Gemcitabine 1000 mg/m2 days (D) 1, 8, Navelbine 20 mg/m2 D1, D8; Doxil 15 mg/m2 Days 1 and 8, G-CSF Days 4-6 and 10-15 (2) Induction Chemo B: Two 21-day cycles of Cyclophosphamide 2000 mg/m2 day 1; Doxorubicin 50 mg/m2 day 1; Vincristine 1.4 mg/m2 day 1; Prednisone 100 mg/m2 days 1-5; Methotrexate 3000 mg/m2 IV over 4h day 15; Leucovorin rescue (3) Disease Evaluation (4) High-dose Consolidation Chemo, high dose Ara-C, Denileukin diftitox (Ontak) and Stem Cell Collection (5) Consolidation Cytarabine 2000 mg/m2 IV over 2 h q 12h days 1-4, Etoposide 40 mg/m2 continuous intravenous infusion (CIVI), days 1-4, Denileukin Diftitox (Ontak) 9 mcg/kg/day days 6-10, G-CSF 10 mcg/kg/day day 14+, Stem cell collection day 22 (6) Autologous Stem Cell Transplant Carmustine 550 mg/m2 day -6, Etoposide 60 mg/kg IV over 4h day -4, Cyclophosphamide 100 mg/kg day -2, Stem cell infusion D0 (7) Post-transplant: Denileukin Diftitox (Ontak) 18 mcg/kg/day days 1- 5

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
February 28, 2008
Last Updated
April 14, 2020
Sponsor
University of California, San Francisco
Collaborators
Eisai Inc., Washington University School of Medicine
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1. Study Identification

Unique Protocol Identification Number
NCT00632827
Brief Title
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

2. Study Status

Record Verification Date
April 2020
Overall Recruitment Status
Terminated
Why Stopped
Manufacturing shortage of both Diftitox and Doxil
Study Start Date
July 1, 2008 (Actual)
Primary Completion Date
June 23, 2014 (Actual)
Study Completion Date
June 23, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of California, San Francisco
Collaborators
Eisai Inc., Washington University School of Medicine

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Peripheral T-Cell Lymphoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Plan
Arm Type
Experimental
Arm Description
(1) Induction Chemo A; Two 21-day cycles of Gemcitabine 1000 mg/m2 days (D) 1, 8, Navelbine 20 mg/m2 D1, D8; Doxil 15 mg/m2 Days 1 and 8, G-CSF Days 4-6 and 10-15 (2) Induction Chemo B: Two 21-day cycles of Cyclophosphamide 2000 mg/m2 day 1; Doxorubicin 50 mg/m2 day 1; Vincristine 1.4 mg/m2 day 1; Prednisone 100 mg/m2 days 1-5; Methotrexate 3000 mg/m2 IV over 4h day 15; Leucovorin rescue (3) Disease Evaluation (4) High-dose Consolidation Chemo, high dose Ara-C, Denileukin diftitox (Ontak) and Stem Cell Collection (5) Consolidation Cytarabine 2000 mg/m2 IV over 2 h q 12h days 1-4, Etoposide 40 mg/m2 continuous intravenous infusion (CIVI), days 1-4, Denileukin Diftitox (Ontak) 9 mcg/kg/day days 6-10, G-CSF 10 mcg/kg/day day 14+, Stem cell collection day 22 (6) Autologous Stem Cell Transplant Carmustine 550 mg/m2 day -6, Etoposide 60 mg/kg IV over 4h day -4, Cyclophosphamide 100 mg/kg day -2, Stem cell infusion D0 (7) Post-transplant: Denileukin Diftitox (Ontak) 18 mcg/kg/day days 1- 5
Intervention Type
Drug
Intervention Name(s)
Gemcitabine
Other Intervention Name(s)
Gemzar
Intervention Description
Chemotherapy medication used to treat a number of types of cancer
Intervention Type
Drug
Intervention Name(s)
Navelbine
Other Intervention Name(s)
Vinorelbine
Intervention Description
Navelbine is an chemotherapy medication used to treat a number of types of cancer
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride Liposome Injection
Other Intervention Name(s)
Doxil
Intervention Description
Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug
Intervention Type
Drug
Intervention Name(s)
Granulocyte-colony stimulating factor (G-CSF)
Other Intervention Name(s)
G-CSF
Intervention Description
G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
Intervention Type
Drug
Intervention Name(s)
Pegfilgrastim
Other Intervention Name(s)
Neulasta
Intervention Description
Colony-stimulating factor 3 (CSF 3) and, is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream. May be used instead of G-CSF
Intervention Type
Drug
Intervention Name(s)
Cyclophosphamide
Other Intervention Name(s)
Cyclophosphamide 2000 MG, Cytoxan
Intervention Description
Cancer medication that interferes with the growth and spread of cancer cells in the body
Intervention Type
Drug
Intervention Name(s)
Vincristine
Other Intervention Name(s)
Vincrex, Vincasar PFS, Oncovin
Intervention Description
Vincristine is a chemotherapy medication used to treat cancer. Vincristine works by stopping the cancer cells from separating into 2 new cells to stops the growth of the cancer
Intervention Type
Drug
Intervention Name(s)
Leucovorin
Other Intervention Name(s)
Wellcovorin
Intervention Description
Leucovorin is used to prevent harmful effects of methotrexate when methotrexate is used to treat certain types of cancer.
Intervention Type
Drug
Intervention Name(s)
Methotrexate
Other Intervention Name(s)
Rheumatrex, Trexall
Intervention Description
Methotrexate is a chemotherapy medication used to treat cancer
Intervention Type
Drug
Intervention Name(s)
Doxorubicin Hydrochloride
Other Intervention Name(s)
Adriamycin
Intervention Description
Doxorubicin Hydrochloride is a chemotherapy medication used to treat cancer
Intervention Type
Drug
Intervention Name(s)
Cytarabine
Other Intervention Name(s)
Ara-C, HiDAC
Intervention Description
Medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma
Intervention Type
Drug
Intervention Name(s)
Etoposide
Other Intervention Name(s)
Etopophos
Intervention Description
Etoposide is a is a chemotherapy medication used to treat cancer
Intervention Type
Drug
Intervention Name(s)
Carmustine
Other Intervention Name(s)
BCNU
Intervention Description
Carmustine is a chemotherapy medication used to treat cancer
Intervention Type
Drug
Intervention Name(s)
Denileukin diftitox
Other Intervention Name(s)
Ontak
Intervention Description
Denileukin diftitox is an antineoplastic agent, an engineered protein combining Interleukin-2 and Diphtheria toxin. Denileukin diftitox could bind to Interleukin-2 receptors and introduce the diphtheria toxin into cells that express those receptors, killing the cells
Primary Outcome Measure Information:
Title
Progression Free Survival
Description
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 Outcome Measure Information:
Title
Overall Survival Rate
Description
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
Title
Complete Response Rate
Description
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
Title
Median Time to Response
Description
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

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lawrence Kaplan, MD
Organizational Affiliation
University of California, San Francisco
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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