Monoclonal Antibody Therapy in Treating Patients With Leukemia - Full Text View

Sponsored by:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00019227

Purpose

RATIONALE: Monoclonal antibodies can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells.

PURPOSE: Phase I/II trial to study the effectiveness of radiolabeled monoclonal antibody plus pentetic acid calcium in patients with leukemia.

Condition	Intervention	Phase
Lymphoma Radiation Toxicity	Drug: pentetic acid calcium Radiation: yttrium Y 90 daclizumab	Phase I Phase II

Study Type:	Interventional
Study Design:	Treatment
Official Title:	PHASE I/II STUDY OF TAC-EXPRESSING ADULT T-CELL LEUKEMIA (ATL) WITH YTTRIUM-90 (90Y)-RADIOLABELED HUMANIZED ANTI-TAC AND CALCIUM-DTPA

Resource links provided by NLM:

MedlinePlus related topics: Calcium Cancer Leukemia, Adult Acute Leukemia, Adult Chronic Lymphoma Radiation Therapy

Drug Information available for: Pentetic acid Calcium trisodium pentetate Zinc-DTPA Dacliximab Immunoglobulins Calcium gluconate Calcium DTPA Globulin, Immune

U.S. FDA Resources

Further study details as provided by National Cancer Institute (NCI):

Study Start Date:

October 1996

Detailed Description:

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00019227

Locations

United States, Maryland
Warren Grant Magnuson Clinical Center - NCI Clinical Studies Support
Bethesda, Maryland, United States, 20892-1182

Sponsors and Collaborators

National Cancer Institute (NCI)

Investigators

Study Chair:

Thomas A. Waldmann, MD

NCI - Metabolism Branch;MET

More Information

Additional Information:

Clinical trial summary from the National Cancer Institute's PDQ® database This link exits the ClinicalTrials.gov site

No publications provided

Study ID Numbers:	CDR0000065240, NCI-96-C-0147K
Study First Received:	July 11, 2001
Last Updated:	May 9, 2009
ClinicalTrials.gov Identifier:	NCT00019227 History of Changes
Health Authority:	United States: Federal Government

Keywords provided by National Cancer Institute (NCI):

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

Study placed in the following topic categories:

Leukemia, Lymphoid
Immunoproliferative Disorders
Immunologic Factors
Daclizumab
Leukemia-Lymphoma, Adult T-Cell
Immunosuppressive Agents
Recurrence
Pentetic Acid
Antibodies, Monoclonal
Leukemia

Lymphatic Diseases
Calcium, Dietary
Antibodies
Immunoglobulin G
Leukemia, T-Cell
Chelating Agents
Lymphoproliferative Disorders
Iron
Lymphoma
Immunoglobulins

Additional relevant MeSH terms:

Leukemia, Lymphoid
Neoplasms by Histologic Type
Immunoproliferative Disorders
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Leukemia-Lymphoma, Adult T-Cell
Daclizumab
Physiological Effects of Drugs
Iron Chelating Agents
Immunosuppressive Agents
Protective Agents

Pharmacologic Actions
Antibodies, Monoclonal
Pentetic Acid
Leukemia
Lymphatic Diseases
Neoplasms
Immunoglobulin G
Leukemia, T-Cell
Chelating Agents
Lymphoproliferative Disorders
Lymphoma
Antidotes

ClinicalTrials.gov processed this record on September 04, 2009