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PHASE I/II STUDY OF TAC-EXPRESSING ADULT T-CELL LEUKEMIA (ATL) WITH YTTRIUM-90 (90Y)-RADIOLABELED HUMANIZED ANTI-TAC AND CALCIUM-DTPA


Phase 1/Phase 2
18 Years
N/A
Not Enrolling
Both
Lymphoma, Radiation Toxicity

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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 SupportBethesda, Maryland  20892-1182