PHASE I/II STUDY OF TAC-EXPRESSING ADULT T-CELL LEUKEMIA (ATL) WITH YTTRIUM-90 (90Y)-RADIOLABELED HUMANIZED ANTI-TAC AND CALCIUM-DTPA
18 Years
N/A
Both
Lymphoma, Radiation Toxicity
Trial Information
PHASE I/II STUDY OF TAC-EXPRESSING ADULT T-CELL LEUKEMIA (ATL) WITH YTTRIUM-90 (90Y)-RADIOLABELED HUMANIZED ANTI-TAC AND CALCIUM-DTPA
OBJECTIVES:
- Determine the maximum tolerated dose of yttrium Y 90 daclizumab (90Y daclizumab) when
combined with pentetic acid calcium in adults with Tac-expressing T-cell leukemia.
- Determine the therapeutic efficacy and toxicity of this regimen in these patients.
- Monitor patients treated on this regimen for circulating infused antibody (free and
labeled) and for the serum concentration of soluble interleukin-2 receptor.
- Evaluate, in a preliminary manner, the immunogenicity of daclizumab.
- Determine the effect of 90Y daclizumab on various components of the circulating
cellular immune system.
- Determine whether there is additional urinary excretion of yttrium Y 90 when compared
to that observed previously in patients treated without pentetic acid calcium.
OUTLINE: This is a dose escalation study of yttrium Y 90 daclizumab (90Y daclizumab).
Patients receive 90Y daclizumab IV over 2 hours on day 1 and a fixed dose of pentetic acid
calcium IV over 5 hours for 3 days. Treatment repeats every 6 weeks for a maximum of 9
courses in the absence of disease progression or circulating antibodies to humanized
anti-Tac.
Cohorts of 3-6 patients receive escalating doses of 90Y daclizumab 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 toxicities. Additional patients are treated at the
MTD.
Patients are followed at 4-6 weeks.
PROJECTED ACCRUAL: Up to 15 patients will be accrued for the phase I portion of the study. A
total of 30 patients will be accrued for the phase II portion of the study.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed adult T-cell leukemia or lymphoma (ATL) of any stage
- Tac expression of malignant cells confirmed by one of the following:
- At least 10% of peripheral blood, lymph node, or dermal malignant cells reactive
with anti-Tac by immunofluorescent staining
- Soluble interleukin-2 receptor levels greater than 1,000 U/mL (normal geometric
mean = 235; 95% confidence intervals = 112-502 U/mL)
- Measurable disease required
- More than 10% (i.e., strongly Tac-expressing) abnormal cells in peripheral blood
considered measurable disease
- All stages of Tac-expressing adult T-cell leukemia are eligible
- Smoldering ATL patients are eligible only if the symptoms and sites of
involvement by ATL are such that there is a medical indication to treat
- Smoldering ATL, defined as:
- Lymphocyte count less than 4,000/mm^3
- Less than 5% abnormal lymphocytes on morphologic exam of peripheral
blood
- No hypercalcemia
- Lactate dehydrogenase no greater than 1.5 times normal
- No lymphadenopathy
- No involvement of extranodal organs except skin or lung
- No malignant pleural effusion or ascites
- No symptomatic CNS disease due to ATL
- Concurrent diagnosis of tropical spastic paraparesis allowed
- No detectable levels (i.e., greater than 250 ng/mL) of antibody to study drug as
assessed by ELISA
PATIENT CHARACTERISTICS:
Age:
- 18 and over
Performance status:
- Not specified
Life expectancy:
- Greater than 2 months
Hematopoietic:
- Absolute granulocyte count at least 1,000/mm^3
- Platelet count at least 75,000/mm^3
Hepatic:
- Bilirubin less than 2.0 mg/dL (unless directly due to ATL)
- AST/ALT less than 2.5 times normal
Renal:
- Creatinine less than 1.5 mg/dL OR
- Creatinine clearance greater than 35 mL/min
Cardiovascular:
- No clinical cardiac failure
Pulmonary:
- No symptomatic pulmonary dysfunction unless due to underlying malignancy
Other:
- HIV negative
- Not pregnant or nursing
- Negative pregnancy test
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- At least 4 weeks since prior cytotoxic chemotherapy
Endocrine therapy
- Concurrent corticosteroids allowed
Radiotherapy
- Not specified
Surgery
- Not specified
Other
- Not specified
Type of Study:
Interventional
Study Design:
Primary Purpose: Treatment
Principal Investigator
Thomas A. Waldmann, MD
Investigator Role:
Study Chair
Investigator Affiliation:
NCI - Metabolism Branch;MET
Authority:
United States: Federal Government
Study ID:
CDR0000065240
NCT ID:
NCT00019227
Start Date:
October 1996
Completion Date:
July 2006
Related Keywords:
- Lymphoma
- Radiation Toxicity
- stage I adult T-cell leukemia/lymphoma
- stage II adult T-cell leukemia/lymphoma
- stage III adult T-cell leukemia/lymphoma
- stage IV adult T-cell leukemia/lymphoma
- recurrent adult T-cell leukemia/lymphoma
- radiation toxicity
- Leukemia
- Leukemia, T-Cell
- Leukemia-Lymphoma, Adult T-Cell
- Lymphoma
- Radiation Injuries
Name | Location |
|---|---|
| Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support | Bethesda, Maryland 20892-1182 |
