Clinical trial NCT00211276: A Study of ONTAK in Patients With Relapsed or Refractory, B-Cell Non Hodgkin's Lymphoma
Official title: A Phase II Multicenter Study of ONTAK in Patients With Relapsed or Refractory, B-Cell Non-Hodgkins Lymphoma.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Lymphoma, B-Cell
Lead sponsor: Eisai Inc.
Sponsor class: INDUSTRY
First posted: 2005-09-21
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this clinical research study is to find out if the study drug, ONTAK (denileukin diftitox), can shrink or slow the growth of B-cell non-Hodgkin's lymphoma (NHL) in patients whose disease has not responded to prior treatments, or has relapsed after an initial response to prior treatments. The safety of treatment with ONTAK will also be studied. The hypothesis is that patients with relapsed or refractory B-cell NHL and mild to moderate myelosuppression treated with ONTAK at a new dosing regimen will respond sufficiently to warrant further study.


Eligibility criteria: Inclusion Criteria:

* Relapsed or refractory B-Cell NHL
* Histological documentation of diffuse large B-cell lymphoma, follicular lymphoma (grade 1, 2, or 3), small lymphocytic lymphoma or transformed B-Cell lymphoma.
* Bi-dimensionally measurable disease with at least one lymph node or tumor mass measuring \> or equal to 4 cm2
* ECOG performance status less than or equal to 2.
* Failure to respond or progression of disease after 2 or more prior treatment regimens; this may include high dose therapy (HDT) with stem cell transplantation (SCT). Patients with prior HDT plus SCT will be considered as having "diminished bone marrow reserve"
* At least 18 years of age
* At least 3 weeks from last anti-lymphoma therapy
* Mild to moderate cytopenia defined as any of the following:
* ANC \> or equal to 1,000/microL and \< 1,500/microL off growth factors
* WBC counts \> or equal to 2,000/microL and \< 4,000/microL off growth factors or
* Platelet count \> or equal to 40,000/microL (25,000/microL if thrombocytopenia is secondary to marrow involvement by lymphoma) and \< 150,000/microL.
* Acceptable organ function defined as all of the following:
* Bilirubin \< or equal to 1.5 times the upper limit of normal (ULN)
* SGOT (AST) and SGPT (ALT) \< or equal to 2 times the ULN.
* Serum creatinine \< 2 times ULN.
* Serum albumin \> or equal to 3.0 g/dL
* Female patient of childbearing potential must have a negative pregnancy test within seven days prior to study drug administration, and must agree to use an effective means of contraception throughout the study.
* Life expectancy of at least 16 weeks.
* Patients must have reviewed, signed and dated a witnessed informed consent document that has been approved by the IRB of each participating center.

Exclusion Criteria:

* Less than 6 months from prior allogeneic stem cell transplant and/or patient with active graft versus host disease (GVHD) Grade \> or equal to 2.
* Prior history of veno-occlusive disease of the liver.
* Inability to comply with protocol requirements of this study for intravenous administration of ONTAK.
* Pregnant women or lactating women who are breastfeeding or women planning to become pregnant during the treatment period.
* Serious intercurrent medical illnesses or active infections that, in the investigators opinion, might interfere with the interpretation of the study safety data or compromise the patients ability to carry out the treatment program.
* Known history of seropositivity for HIV or chronic hepatitis (testing for HIV is not required).
* Known hypersensitivity to ONTAK or any of its components: diptheria toxin, interleukin-2 or excipients.
* Experimental therapy within 4 weeks prior to study entry.
* Patients diagnosed with congestive heart failure, NYHA Class III or IV, ventricular tachycardia, fibrillation, or a history of myocardial infarction in the 12 months prior to study entry.
* Any prior radiation therapy within four weeks of enrollment, or prior radiation therapy to the only site of evaluable disease unless disease progression has occurred in that site.
* Patients on concurrent corticosteroids as treatment for NHL. The use of tapering doses or low doses of corticosteroids for resolving GVHD, or the use of corticosteroids as premedication prior to ONTAK or as a transient treatment for hypersensitivity reactions is permitted as necessary.
* History of prior malignancy within the preceding 5 years, except for successfully treated cervical carcinoma in situ or basal cell carcinoma.

Primary outcomes:
measure: Disease Response will be evaluated by CT or MRI scans at baseline, every 8 weeks while on therapy, and every 3 months after therapy, using standard response criteria defined by Cheson et al.
Secondary outcomes:
measure: Safety data will include laboratory, history and physical, and adverse events reports for both local and systemic signs or symptoms of study patients. Survival at one year post-therapy will also be assessed.
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Tower Cancer Research Foundation
state: California
city: Fountain Valley
country: United States
facility: Pacific Coast Hematology/Oncology
state: California
city: Los Angeles
country: United States
facility: University of California, Los Angeles
state: California
city: Atlanta
country: United States
facility: Emory University
state: Georgia
city: Chicago
country: United States
facility: Rush University Medical Center
state: Illinois
city: Sioux City
country: United States
facility: Siouxland Hematology-Oncology
state: Iowa
city: St. Louis
country: United States
facility: Washington University Siteman Cancer Center
state: Missouri
city: Hackensack
country: United States
facility: Hackensack University Medical Center
state: New Jersey
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: St. Vincent's Comprehensive Cancer Center
state: New York
city: Cleveland
country: United States
facility: Case Comprehensive Cancer Center
state: Ohio
city: Pittsburgh
country: United States
facility: The Western Pennsylvania Hospital
state: Pennsylvania
Study officials:
affiliation: Roswell Park Cancer Institute
name: Myron Czuczman, MD
role: PRINCIPAL_INVESTIGATOR
References: