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

Lymphoma Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00138164
• Other study ID #: LIGAND-PIND-123
• Secondary ID: UCLA-0412087-01C
• Status: Completed
• Phase: Phase 2
• First received: August 29, 2005
• Last updated: May 29, 2013
• Start date: December 2004
• Est. completion date: November 2008

Study information

• Verified date: November 2008
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 50
• Est. completion date: November 2008
• Est. primary completion date: February 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lymphoma
• Lymphoma, Non-Hodgkin

Intervention

Biological:
• denileukin diftitox

Locations

Country	Name	City	State
United States	Jonsson Comprehensive Cancer Center at UCLA	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
Jonsson Comprehensive Cancer Center	National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Objective clinical response (complete or partial response)			No
Secondary	Time to progression			No
Secondary	Overall survival at 1 year			No
Secondary	Safety			Yes