Clinical trial NCT00138164: Denileukin Diftitox in Treating Patients With Relapsed or Refractory Non-Hodgkin's Lymphoma
Official title: A Phase II Multicenter Study of Ontak® (Denileukin Diftitox) in Patients With Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma
Keywords: 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
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
Collaborators: name: National Cancer Institute (NCI)
First posted: 2005-08-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective clinical response (complete or partial response)
Secondary outcomes:
measure: Time to progression
measure: Overall survival at 1 year
measure: Safety
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jonsson Comprehensive Cancer Center at UCLA
state: California
Study officials:
affiliation: Jonsson Comprehensive Cancer Center
name: Lauren C. Pinter-Brown, MD
role: PRINCIPAL_INVESTIGATOR
References: