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

University of California San Francisco (UCSF)

Status and phase

Terminated

Phase 2

Conditions

Peripheral T-Cell Lymphoma

Treatments

Drug: Denileukin diftitox

Drug: Doxorubicin Hydrochloride

Drug: Carmustine

Drug: Granulocyte-colony stimulating factor (G-CSF)

Drug: Pegfilgrastim

Drug: Etoposide

Drug: Vincristine

Drug: Navelbine

Drug: Doxorubicin Hydrochloride Liposome Injection

Drug: Cyclophosphamide

Drug: Methotrexate

Drug: Cytarabine

Drug: Gemcitabine

Drug: Leucovorin

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00632827

NCI-2011-01285 (Registry Identifier)

072518

Details and patient eligibility

About

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

Full 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.

Enrollment

21 patients

Sex

All

Ages

18 to 70 years old

Volunteers

No 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

Trial design

Primary purpose

Treatment

Allocation

N/A

Interventional model

Single Group Assignment

Masking

None (Open label)

21 participants in 1 patient group

Treatment Plan

Experimental group

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

Treatment: