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

NCT00632827 | Terminated Phase 2 Results DMC FDA Drug

• 2 other identifiers: 072518NCI-2011-01285
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Peripheral T-Cell Lymphoma

Outcome Measures

Primary Outcomes (1)

• 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

  Up to 3 years

Secondary Outcomes (3)

• Overall Survival Rate

  Up to 5 years

• Complete Response Rate

  Up to 3 years

• Median Time to Response

  Up to 2 years

Study Arms (1)

Treatment Plan

EXPERIMENTAL

(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

Drug: Gemcitabine; Drug: Navelbine; Drug: Doxorubicin Hydrochloride Liposome Injection; Drug: Granulocyte-colony stimulating factor (G-CSF); Drug: Pegfilgrastim; Drug: Cyclophosphamide; Drug: Vincristine; Drug: Leucovorin; Drug: Methotrexate; Drug: Doxorubicin Hydrochloride; Drug: Cytarabine; Drug: Etoposide; Drug: Carmustine; Drug: Denileukin diftitox

Interventions

Gemcitabine DRUG

Chemotherapy medication used to treat a number of types of cancer

Also known as: Gemzar

Treatment Plan

Navelbine DRUG

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

Also known as: Vinorelbine

Treatment Plan

Doxorubicin Hydrochloride Liposome Injection DRUG

Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug

Also known as: Doxil

Treatment Plan

Granulocyte-colony stimulating factor (G-CSF) DRUG

G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.

Also known as: G-CSF

Treatment Plan

Pegfilgrastim DRUG

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

Also known as: Neulasta

Treatment Plan

Cyclophosphamide DRUG

Cancer medication that interferes with the growth and spread of cancer cells in the body

Also known as: Cyclophosphamide 2000 MG, Cytoxan

Treatment Plan

Vincristine DRUG

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

Also known as: Vincrex, Vincasar PFS, Oncovin

Treatment Plan

Leucovorin DRUG

Leucovorin is used to prevent harmful effects of methotrexate when methotrexate is used to treat certain types of cancer.

Also known as: Wellcovorin

Treatment Plan

Methotrexate DRUG

Methotrexate is a chemotherapy medication used to treat cancer

Also known as: Rheumatrex, Trexall

Treatment Plan

Doxorubicin Hydrochloride DRUG

Doxorubicin Hydrochloride is a chemotherapy medication used to treat cancer

Also known as: Adriamycin

Treatment Plan

Cytarabine DRUG

Medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma

Also known as: Ara-C, HiDAC

Treatment Plan

Etoposide DRUG

Etoposide is a is a chemotherapy medication used to treat cancer

Also known as: Etopophos

Treatment Plan

Carmustine DRUG

Carmustine is a chemotherapy medication used to treat cancer

Also known as: BCNU

Treatment Plan

Denileukin diftitox DRUG

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

Also known as: Ontak

Treatment Plan

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:

You may not qualify if:

• 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• Eisai Inc.: collaborator
• Washington University School of Medicine: collaborator

Study Sites (1)

Washington University

St Louis, Missouri, 63110, United States

Location

MeSH Terms

Conditions

Lymphoma, T-Cell, Peripheral

Interventions

Gemcitabine; Vinorelbine; liposomal doxorubicin; Granulocyte Colony-Stimulating Factor; pegfilgrastim; Cyclophosphamide; Vincristine; Leucovorin; Methotrexate; Doxorubicin; Cytarabine; Etoposide; etoposide phosphate; Carmustine; denileukin diftitox

Condition Hierarchy (Ancestors)

Lymphoma, T-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Vinca Alkaloids; Secologanin Tryptamine Alkaloids; Indole Alkaloids; Alkaloids; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Indolizidines; Indolizines; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Coenzymes; Enzymes and Coenzymes; Aminopterin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Polycyclic Compounds; Aminoglycosides; Glycosides; Arabinonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Glucosides; Nitrosourea Compounds; Urea; Amides; Nitroso Compounds

Limitations and Caveats

Enrollment was terminated prematurely due to manufacturing shortages of Doxil and Denileukin Diftitox (Ontak). All eligible patients who received at least one dose of study regimen were included in the analyses

Results Point of Contact

• Title: Lawrence Kaplan, MD
• Organization: University of California, San Francisco

LKaplan@ucsf.edu

(415) 353-2661

Study Officials

• Lawrence Kaplan, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 28, 2008
• First Posted: March 11, 2008
• Study Start: July 1, 2008
• Primary Completion: June 23, 2014
• Study Completion: June 23, 2016
• Last Updated: April 27, 2020
• Results First Posted: April 27, 2020

Record last verified: 2020-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)