Denileukin Diftitox in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma

This study has been completed.
Information provided by:
National Cancer Institute (NCI) Identifier:
First received: August 29, 2005
Last updated: May 29, 2013
Last verified: November 2008

RATIONALE: Biological therapies, such as denileukin diftitox, may be able to carry cancer-killing substances directly to non-Hodgkin's lymphoma cells.

PURPOSE: This phase II trial is studying how well denileukin diftitox works in treating patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.

Condition Intervention Phase
Biological: denileukin diftitox
Phase 2

Study Type: Interventional
Study Design: Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Multicenter Study of Ontak® (Denileukin Diftitox) in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Objective clinical response (complete or partial response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Time to progression [ Designated as safety issue: No ]
  • Overall survival at 1 year [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]

Estimated Enrollment: 50
Study Start Date: December 2004
Study Completion Date: November 2008
Primary Completion Date: February 2006 (Final data collection date for primary outcome measure)
Detailed Description:



  • Determine the efficacy of denileukin diftitox, in terms of objective response and time to progression, in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma.


  • Determine the safety of this drug in these patients.
  • Determine the 1-year overall survival of patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive denileukin diftitox IV over 20-80 minutes on days 1-3, 8, 15, 22, 29, 36, 43, 50, 57, 64, 71, 78, 85, 92, and 99 (weeks 1-16) in the absence of disease progression or unacceptable toxicity. Patients achieving a partial response at week 16 may continue treatment once monthly for up to 8 additional doses or until a complete response (CR) is achieved. Patients achieving a CR (at any time) receive 2 additional monthly doses of denileukin diftitox beyond CR.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 25-50 patients will be accrued for this study within 1 year.


Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No


  • Histologically confirmed B-cell non-Hodgkin's lymphoma (NHL) of 1 of the following subtypes:

    • Diffuse large B-cell lymphoma
    • Follicular lymphoma (grades 1-3)
    • Small lymphocytic lymphoma
    • Transformed B-cell lymphoma
  • Relapsed or refractory disease

    • Disease failed to respond to or progressed after ≥ 2 prior treatment regimens (e.g., high-dose therapy [HDT] with stem cell transplantation [SCT]*) NOTE: *Patients who have received HDT with SCT are considered to have diminished bone marrow reserve
  • Diminished bone marrow reserve AND/OR mild to moderate cytopenia, meeting 1 of the following criteria:

    • Absolute neutrophil count ≥ 1,000/mm^3 but < 1,500/mm^3 (growth factor independent)
    • WBC ≥ 2,000/mm^3 but < 4,000/mm^3 (growth factor independent)
    • Platelet count ≥ 40,000/mm^3 (25,000/mm^3 if thrombocytopenia is secondary to marrow involvement by lymphoma) but < 150,000/mm^3 (platelet transfusion independent)
  • At least 1 bidimensionally measurable lymph node or tumor mass ≥ 4 cm



  • 18 and over

Performance status

  • ECOG 0-2

Life expectancy

  • At least 16 weeks


  • See Disease Characteristics


  • Bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST and ALT ≤ 2 times ULN
  • Albumin ≥ 3.0 g/dL
  • No history of veno-occlusive disease of the liver
  • No chronic hepatitis


  • Creatinine < 2 times ULN


  • No congestive heart failure
  • No New York Heart Association class III-IV cardiac disease
  • No ventricular tachycardia
  • No fibrillation
  • No myocardial infarction within the past 12 months


  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No known HIV positivity
  • No active GVHD ≥ grade 2 within the past 6 months
  • No other serious medical illness or active infection that would preclude study participation
  • No known hypersensitivity to denileukin diftitox or any of its components (e.g., diphtheria toxin, interleukin-2, or their excipients)
  • No other malignancy within the past 5 years except successfully treated carcinoma in situ of the cervix or basal cell carcinoma


Biologic therapy

  • See Disease Characteristics
  • At least 6 months since prior allogeneic SCT
  • No concurrent immunotherapy


  • No concurrent chemotherapy

Endocrine therapy

  • No concurrent anticancer hormonal therapy
  • No concurrent corticosteroids for the treatment of NHL
  • Concurrent corticosteroids allowed for the following conditions:

    • Tapering doses of corticosteroids for resolving graft-versus-host disease (GVHD)
    • Low-dose maintenance corticosteroids for the treatment of an autoimmune disorder
    • Corticosteroids as premedication prior to denileukin diftitox administration or as transient treatment for hypersensitivity reactions


  • More than 4 weeks since prior and no concurrent radiotherapy
  • No prior radiotherapy to the only site of evaluable disease unless disease progression has occurred at that site


  • Not specified


  • At least 3 weeks since prior antilymphoma therapy
  • More than 4 weeks since prior and no other concurrent experimental therapy, including approved drugs tested in an investigational setting
  Contacts and Locations
Please refer to this study by its identifier: NCT00138164

United States, California
Jonsson Comprehensive Cancer Center at UCLA
Los Angeles, California, United States, 90095-1781
Sponsors and Collaborators
Jonsson Comprehensive Cancer Center
Principal Investigator: Lauren C. Pinter-Brown, MD Jonsson Comprehensive Cancer Center
  More Information

Additional Information:
No publications provided Identifier: NCT00138164     History of Changes
Other Study ID Numbers: LIGAND-PIND-123, UCLA-0412087-01, CDR0000439451
Study First Received: August 29, 2005
Last Updated: May 29, 2013
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
recurrent adult diffuse large cell lymphoma
recurrent grade 1 follicular lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent small lymphocytic lymphoma

Additional relevant MeSH terms:
Lymphoma, Non-Hodgkin
Lymphoma, B-Cell
Neoplasms by Histologic Type
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Denileukin diftitox
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents processed this record on April 17, 2014