Acute T-Cell Leukemia-Lymphoma Clinical Trial
Official title:
Phase II Study of the Efficacy and Toxicity of Campath-1H in the Therapy of Adult T-Cell Leukemia
This study will examine the safety and effectiveness of Alemtuzumab (Campath-1H) for
treating patients with adult T-cell leukemia/lymphoma (ATL). ATL is caused by a virus called
human T-cell lymphotrophic virus type-1 (HTLV-1) that infects lymphocytes (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, computed tomography (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 (if skin disease is present) 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 biopsy: This procedure may be done to document or monitor disease progress.
Patients receive treatment for up to 12 weeks. Treatment may stop earlier 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.
| Status | Completed |
| Enrollment | 29 |
| Est. completion date | July 2012 |
| Est. primary completion date | July 2009 |
| Accepts healthy volunteers | No |
| Gender | Both |
| Age group | 18 Years and older |
| Eligibility |
Inclusion Criteria: - Patients must have serum antibodies directed to Human T-lymphotropic Virus Type 1 (HTLV-1). - 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 Acute T-cell leukemia/lymphoma (ATL) are eligible. - Patients must have measurable disease. All patients with greater than 10% abnormal (i.e. Tac homogeneous strongly expressing) peripheral blood mononuclear cell (PBMC)in the peripheral blood will be deemed to have measurable disease. - The patient must have a granulocyte count of at least 100/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 serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (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-1-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. - Human immunodeficiency virus (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 with previously received Campath-1GH are ineligible. |
Allocation: Non-Randomized, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
| Country | Name | City | State |
|---|---|---|---|
| United States | National Institutes of Health, National Cancer Institute | Bethesda | Maryland |
| Lead Sponsor | Collaborator |
|---|---|
| National Cancer Institute (NCI) |
United States,
Catane R, Longo DL. Monoclonal antibodies for cancer therapy. Isr J Med Sci. 1988 Sep-Oct;24(9-10):471-6. Review. — View Citation
Dickman S. Antibodies stage a comeback in cancer treatment. Science. 1998 May 22;280(5367):1196-7. — View Citation
Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. Biotechnology. 1992;24:524-6. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall Response Rate | Overall response rate is defined as the percentage of participants with response and utilizes the International Standardized workshop definition. Complete response(CR)-Complete disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease related symptoms if present before therapy and normalization of those biochemical abnormalities (for example LDH) definitely assignable to the lymphoma. Please see the protocol Link module for the full criteria if desired. |
60 months | No |
| Primary | Overall Survival | Time between the first day of treatment to the day of death. | 60 months | No |
| Primary | Time to Progression | Time between the first day of treatment to the day of disease progression which is defined as a persistent (at least two determinations) doubling of the peripheral blood leukemic cell count, the development of new lesions, or Ca elevations that are uncontrolled by conventional therapeutic procedures. | 60 months | No |
| Secondary | Cell Surface Expression of CD52 on Tumor Cells | The CD52 antibody-binding capacity (ABC) value is the measurement of the mean value of the maximum capacity of each cell to bind the anti-CD52 and when determined under conditions of saturating levels of antibody measures number of mean surface CD52 antigens per cell. CD52 ABC is negative when 100% saturation by therapeutic antibody is achieved. | 6 months | No |
| Secondary | The Number of Participants With Adverse Events | Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module. | 18 months | Yes |