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

Peripheral T-Cell Lymphoma Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00632827
• Other study ID #: 072518
• Secondary ID: NCI-2011-01285
• Status: Terminated
• Phase: Phase 2
• Start date: July 1, 2008
• Est. completion date: June 23, 2016

Study information

• Verified date: April 2020
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: June 23, 2016
• Est. primary completion date: June 23, 2014
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, T-Cell
• Lymphoma, T-Cell, Peripheral
• Peripheral T-Cell Lymphoma

Intervention

Drug:
• Gemcitabine
Chemotherapy medication used to treat a number of types of cancer
• Navelbine
Navelbine is an chemotherapy medication used to treat a number of types of cancer
• Doxorubicin Hydrochloride Liposome Injection
Doxorubicin Hydrochloride Liposome Injection is an anti-cancer chemotherapy drug
• Granulocyte-colony stimulating factor (G-CSF)
G-CSF is a glycoprotein that stimulates the bone marrow to produce granulocytes and stem cells and release them into the bloodstream.
• Pegfilgrastim
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
• Cyclophosphamide
Cancer medication that interferes with the growth and spread of cancer cells in the body
• Vincristine
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
• Leucovorin
Leucovorin is used to prevent harmful effects of methotrexate when methotrexate is used to treat certain types of cancer.
• Methotrexate
Methotrexate is a chemotherapy medication used to treat cancer
• Doxorubicin Hydrochloride
Doxorubicin Hydrochloride is a chemotherapy medication used to treat cancer
• Cytarabine
Medication used to treat acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), chronic myelogenous leukemia (CML), and non-Hodgkin's lymphoma
• Etoposide
Etoposide is a is a chemotherapy medication used to treat cancer
• Carmustine
Carmustine is a chemotherapy medication used to treat cancer
• Denileukin diftitox
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

Locations

Country	Name	City	State
United States	Washington University	Saint Louis	Missouri

Sponsors (3)

Lead Sponsor	Collaborator
University of California, San Francisco	Eisai Inc., Washington University School of Medicine

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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.	Up to 5 years
Secondary	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.	Up to 3 years
Secondary	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.	Up to 2 years