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

A Phase II Multicenter Study of Ontak® (Denileukin Diftitox) in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma

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.

Study Overview

• Status: Completed
• Conditions: Lymphoma
• Intervention / Treatment: Biological: denileukin diftitox

Detailed Description

OBJECTIVES:

Primary

• 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.

Secondary

• 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.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Los Angeles, California, United States, 90095-1781
      • Jonsson Comprehensive Cancer Center at UCLA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

DISEASE CHARACTERISTICS:

• 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

PATIENT CHARACTERISTICS:

Age

• 18 and over

Performance status

• ECOG 0-2

Life expectancy

• At least 16 weeks

Hematopoietic

• See Disease Characteristics

Hepatic

• 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

Renal

• Creatinine < 2 times ULN

Cardiovascular

• 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

Other

• 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

PRIOR CONCURRENT THERAPY:

Biologic therapy

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

Chemotherapy

• 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

Radiotherapy

• 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

Surgery

• Not specified

Other

• 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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Objective clinical response (complete or partial response)

Secondary Outcome Measures

Outcome Measure
Time to progression
Safety
Overall survival at 1 year

Collaborators and Investigators

• Sponsor: Jonsson Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Lauren C. Pinter-Brown, MD, Jonsson Comprehensive Cancer Center

Study record dates

Study Major Dates

• Study Start: December 1, 2004
• Primary Completion (Actual): February 1, 2006
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: August 29, 2005
• First Submitted That Met QC Criteria: August 29, 2005
• First Posted (Estimate): August 30, 2005

Study Record Updates

• Last Update Posted (Estimate): May 30, 2013
• Last Update Submitted That Met QC Criteria: May 29, 2013
• Last Verified: November 1, 2008

More Information

Terms related to this study

• Keywords: recurrent grade 3 follicular lymphoma; recurrent adult diffuse large cell lymphoma; recurrent grade 1 follicular lymphoma; recurrent grade 2 follicular lymphoma; recurrent small lymphocytic lymphoma
• Additional Relevant MeSH Terms: Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Lymphoma; Lymphoma, Non-Hodgkin; Antineoplastic Agents; Denileukin diftitox
• Other Study ID Numbers: LIGAND-PIND-123; UCLA-0412087-01; CDR0000439451 (Registry Identifier: PDQ (Physician Data Query))