Clinical trial NCT00024115: BL22 Immunotoxin in Treating Patients With Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Official title: Phase I Study of Recombinant BL22 Immunotoxin in Patients With CD22-Positive B-Cell Non-Hodgkin's Lymphoma or Chronic Lymphocytic Leukemia
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Keywords: refractory chronic lymphocytic leukemia
B-cell chronic lymphocytic leukemia
stage III grade I follicular small cleaved cell lymphoma
stage III grade II follicular mixed cell lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage IV grade I follicular small cleaved cell lymphoma
stage IV grade II follicular mixed cell lymphoma
stage IV adult diffuse small cleaved cell lymphoma
recurrent grade I follicular small cleaved cell lymphoma
recurrent grade II follicular mixed cell lymphoma
recurrent grade III follicular large cell lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
recurrent adult diffuse small noncleaved cell/Burkitt's lymphoma
prolymphocytic leukemia
contiguous stage II grade I follicular small cleaved cell lymphoma
contiguous stage II grade II follicular mixed cell lymphoma
contiguous stage II adult diffuse small cleaved cell lymphoma
noncontiguous stage II grade I follicular small cleaved cell lymphoma
noncontiguous stage II grade II follicular mixed cell lymphoma
noncontiguous stage II adult diffuse small cleaved cell lymphoma
stage III diffuse small lymphocytic/marginal zone lymphoma
contiguous stage II diffuse small lymphocytic/marginal zone lymphoma
noncontiguous stage II diffuse small lymphocytic/marginal zone lymphoma
stage IV diffuse small lymphocytic/marginal zone lymphoma
recurrent diffuse small lymphocytic/marginal zone lymphoma
recurrent mantle cell lymphoma
Lead sponsor: National Cancer Institute (NCI)
Sponsor class: NIH
First posted: 2003-01-27
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: RATIONALE: The BL22 immunotoxin can locate tumor cells and kill them without harming normal cells.

PURPOSE: Phase I trial to study the effectiveness of the BL22 immunotoxin in treating patients who have non-Hodgkin's lymphoma or chronic lymphocytic leukemia.

Detailed description: OBJECTIVES:

* Determine the toxicity and therapeutic efficacy of recombinant BL22 immunotoxin in patients with CD22-positive B-cell non-Hodgkin's lymphoma or chronic lymphocytic leukemia.
* Determine the pharmacokinetics, including the terminal elimination serum half-life area under the curve and volume of distribution, of recombinant BL22 immunotoxin in these patients.
* Determine the immunogenicity of recombinant BL22 immunotoxin in these patients.
* Determine the effect of recombinant BL22 immunotoxin on various components of the circulating cellular immune system in these patients.

OUTLINE: This is a dose-escalation study.

Patients receive recombinant BL22 immunotoxin IV over 30 minutes on days 1, 3, and 5. Patients may be retreated at least every 20 days for up to 25 courses in the absence of disease progression and sufficient neutralizing antibodies.

Cohorts of 3-6 patients receive escalating doses of recombinant BL22 immunotoxin until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 6 patients experience dose-limiting toxicity.

PROJECTED ACCRUAL: A total of 40 patients will be accrued for this study within 2 years.

Eligibility criteria: DISEASE CHARACTERISTICS:

* Histologically confirmed chronic lymphocytic leukemia or prolymphocytic leukemia:
* Failed prior standard chemotherapy and treatment is medically indicated as evidenced by the following:
* Progressive disease-related symptoms
* Progressive cytopenias due to marrow involvement
* Progressive or painful splenomegaly or adenopathy
* Rapidly increasing lymphocytosis
* Autoimmune hemolytic anemia or thrombocytopenia
* Increased frequency of infections OR
* Confirmed CD22+ B-cell indolent non-Hodgkin's lymphoma
* Stages II-IV that have failed at least 1 prior standard therapy and treatment is medically indicated
* No patients whose serum neutralizes BL22 or PE38 in tissue culture, due to antitoxin or antimouse-IgG antibodies
* No central nervous system disease requiring treatment
* If the patient is non-leukemic, the absolute neutrophil count must be greater than 1,000/mm3 and the platelet count greater than 40,000/mm3

PATIENT CHARACTERISTICS:

Age:

* 18 and over

Performance status:

* Karnofsky 60-100%

Life expectancy:

* More than 6 months

Hematopoietic:

* See Disease Characteristics

Hepatic:

* ALT and AST less than 5 times upper limit of normal

Renal:

* Adequate renal function

Pulmonary:

* Adequate pulmonary function

Other:

* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* HIV negative

PRIOR CONCURRENT THERAPY:

Biologic therapy:

* Prior bone marrow transplantation allowed
* At least 3 weeks since prior interferon for malignancy

Chemotherapy:

* See Disease Characteristics
* At least 3 weeks since prior cytotoxic chemotherapy for malignancy

Endocrine therapy:

* Not specified

Radiotherapy:

* At least 3 weeks since prior radiotherapy for malignancy

Surgery:

* Not specified

Other:

* At least 3 weeks since prior retinoids
* At least 3 weeks since prior systemic therapy for cancer

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Bethesda
country: United States
facility: Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
state: Maryland
Study officials:
affiliation: National Cancer Institute (NCI)
name: Robert Kreitman, MD
role: STUDY_CHAIR
References: