Protocol Number: 03-C-0194

Title:

Phase II Study of the Efficacy and Toxicity of Campath-1H in the Therapy of Adult T-Cell Leukemia

Number:

03-C-0194

Summary:

This study will examine the safety and effectiveness of Campath-1H for treating patients with adult T-cell leukemia/lymphoma (ATL). ATL is caused by a virus called HTLV-1 that infects lymphoctyes (white blood cells) called T-cells. Cancerous cells can be found not only in the blood, but also in the skin, lungs, lymph nodes, liver, bone, bone marrow, spleen, and meninges (tissues covering the brain). There are four categories of ATL, based on the aggressiveness of disease-smoldering, chronic, lymphoma, and acute. Campath-1H is a monoclonal antibody that attaches to and kills normal and cancerous lymphocytes, including T cells. Although Campath-1H is an experimental drug for treating ATL, it is approved by the Food and Drug Administration for treating chronic lymphocytic leukemia.

Patients 18 years of age and older with any type of ATL except smoldering may be eligible for this study. Candidates are screened with a medical history and physical examination, photos of skin lesions, measurement of lesions such as lymph nodes and skin nodules, blood and urine tests, electrocardiogram (EKG), chest x-ray, CT scan or ultrasound of the abdomen, skin biopsy, bone marrow aspirate and biopsy, skin test, and lumbar puncture (spinal tap). Participants undergo treatment in two phases, as follows:

-Dose escalation phase: Patients receive an infusion of Campath-1H daily for three days. The initial dose is low and is increased daily as long as there are no side effects, or only mild reactions, until the patient is receiving the maximum dose of 30 milligrams per day.

-Stable dose phase: Patients receive infusions of Campath-1H 30 mg three times a week for up to 12 weeks.

In addition to treatment, patients are evaluated with the following tests and procedures:

-History and physical examination every 4 weeks.

-Blood tests every 4 weeks.

-CT scans to measure the size of the tumors every 4 weeks.

-Skin biopsies and lymph note aspirates: Up to five biopsies and five aspirates may be taken to help diagnose the disease and evaluate the effect of Campath-1H on the cancer.

-Bone marrow or lymph node biopsy: These procedures may be done to document or monitor disease progress.

Patients receive treatment for up to 12 weeks. Treatment may stop earlier if the patient's condition worsens or if the patient achieves a complete response before the end of 12 weeks. Patients completing the study are followed periodically with a history and physical examination, blood and urine tests, tumor evaluation, skin biopsy and skin testing. They are seen monthly at first and then at 3-month intervals the first year; every 4 months the second year, every 6 months for the third through fifth years, and then yearly.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

Patients must have serum antibodies directed to HTLV-I.

All patients must have a histologically confirmed diagnosis of adult T-cell leukemia/lymphoma and more than 10% of the malignant cells must express CD52 and CD25.

All stages of Tac-expressing adult T-cell leukemia except smoldering are eligible: patients with chronic, lymphoma or acute ATL are eligible.

Patients must have measurable disease. All patients with greater than 10% abnormal (i.e., Tac homogenous strongly expressing) PBMC in the peripheral blood will be deemed to have measurable disease.

The patient must have a granulocyte count of at least 1000/mm(3) and a platelet count of greater than or equal to 50,000/mm(3).

Patients must have a creatinine of less than 3.0 mg/dl.

Omission of cytotoxic chemotherapy for ATL for 3 weeks prior to entry into the trial is required. However patients receiving a stable dose of corticosteroids for at least three to four weeks without evidence of tumor response will be eligible.

Patients must have a life expectancy of greater than 2 months.

Eligible patients must be greater than or equal to 18 years old. There is no upper age limit.

Patients must have SGOT and SGPT value less than or equal to 2.5-fold greater than the upper limit of normal and bilirubin less than or equal to 3.0/dl. If a liver function test is judged to be elevated due to the underlying ATL, this parameter will be considered an unevaluable parameter for toxicity determinations.

Patients must be able to understand and sign an Informed Consent form.

All patients must use adequate contraception during participation in this trial and for three months after completing therapy.

EXCLUSION CRITERIA:

Patients with symptomatic leukemic meningitis will be excluded. However, patients that have both ATL and another HTLV-I-associated disease, tropical spastic paraparesis (TSP), will be included.

Pregnant and nursing patients are not eligible for the study. Because the effects of CAMPATH-1H on the developing fetus are unknown pregnant women will be excluded. Breast-feeding in patients with HTLV-1 infection is contraindicated because of the risk of transmission of the virus to the child. In addition, CAMPATH-1H may be present in breast milk and produce adverse events in the breast-feeding child.

HIV positive patients are excluded from the study. CAMPATH-1H may produce a different pattern of toxicities in patients with HIV infection and in addition the depletion of T cells produced by CAMPATH-1H may have adverse effects on HIV positive individuals.

Patients with smoldering ATL are excluded.

Patients who previously received Campath-1GH are ineligible.

Special Instructions:

Currently Not Provided

Keywords:

Monoclonal Antibody

HTLV-1

CD52

Flow Cytometry

Antibody Saturation

Recruitment Keyword(s):

Adult T-Cell Leukemia (ATL)

ATL

Condition(s):

Acute T-Cell Leukemia-Lymphoma

Investigational Drug(s):

Campath-1H

Investigational Device(s):

None

Intervention(s):

Drug: Campath-1H

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. Biotechnology. 1992;24:524-6.

Catane R, Longo DL. Monoclonal antibodies for cancer therapy. Isr J Med Sci. 1988 Sep-Oct;24(9-10):471-6.

Dickman S. Antibodies stage a comeback in cancer treatment. Science. 1998 May 22;280(5367):1196-7.

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