Neoplasms

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Rare Diseases

Lymphoma

Leukemia

Leukemia, T-Cell

Precursor T-Cell Lymphoblastic Leukemia-Lymphoma

Leukemia-Lymphoma, Adult T-Cell

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Leukemia, Lymphoid

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hematologic Diseases

Lymphosarcoma

Acute Graft Versus Host Disease

Adult T-cell Leukemia/lymphoma

Human T-cell Leukemia Virus Type 1

Leukemia, T-cell, Chronic

Acute Lymphoblastic Leukemia

Lymphoblastic Lymphoma

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Immunoglobulins

Alemtuzumab

Antineoplastic Agents, Immunological

Infusion of Campath-1H 3 mg on day # 1, 10 mg on day #2, and 30 mg day # 3 followed by maintenance Campath-1H 30 mg intravenously three times per week.

Infusion of Campath-1H 3 mg on day # 1, 10 mg on day #2, and 30 mg day # 3 followed by maintenance Campath-1H 30 mg intravenously three times per week. Patients are eligible to receive a maximum of 12 weeks of maintenance Campath-1H treatment.

Thomas A Waldmann, M.D.

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.

Background:

Adult T-cell leukemia/lymphoma (ATL) is an aggressive lymphoproliferative disorder caused by an infection with the human T-cell lymphotrophic virus type-1 (HTLV-1).

ATL is characterized by rapidly rising peripheral blood leukemia cell counts, lymphadenopathy, lytic bone lesions, hepatosplenomegaly, and skin and solid organ involvement by tumor.

Chemotherapy has shown modest activity and the treatment of ATL has remained largely undefined and the survival of ATL patients poor.

The CD52 surface glycoantigen is overexpressed on ATL cells.

Alemtuzumab (Campath-1H) is a humanized rat monoclonal antibody that binds to CD52 and is cytotoxic.

In preclinical models, Campath-1H inhibited tumor growth and improved the survival of Non-obese diabetic (NOD)/severe combined immune deficiency (SCID) mice injected with human MET-1 ATL cells.

Objectives:

To determine the efficacy of Campath-1H in the treatment of ATL.

To define the time course of Campath-1H saturation in patients with ATL.

To define the toxicity of Campath-1H in patients with ATL.

Eligibility:

Patients with HTLV-I-associated adult T-cell leukemia.

More than 10% of the malignant cells must express CD52 and CD25.

Patients must 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).

Design:

A single institution non-randomized open-label Phase II trial.

This trial will recruit a maximum of 30 eligible patients.

Patients will receive antimicrobial and antiviral prophylaxis while on-study due to the known immunosuppressive effects of Campath-1H.

Patients will receive I.V. Campath-1H 3 mg on day 1, 10 mg on day 2, and 30 mg day 3 followed by maintenance Campath-1H 30 mg I.V. three time per week.

Patients will be evaluated for response and continuation of Campath-1H therapy after weeks 4 and 8 of maintenance treatment.

Patients are eligible to receive a maximum of 12 weeks of maintenance Campath-1H treatment.

Campath-1H for Treating Adult T-Cell Leukemia/Lymphoma

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

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.

Time between the first day of treatment to the day of death.

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.

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.

Here are the total number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

National Cancer Institute (NCI)

Thomas A. Waldmann, M.D.

Intravenous Campath-1H 3 mg on day #1, 10mg on day #2, and 30mg on day #3 followed by maintenance Campath-1H 30 mg intravenously three times per week. Patients are eligible to receive a maximum of 12 weeks of maintenance Campath-1H treatment.

Campath-1H Treatment of Adult T-cell Leukemia (ATL)

Age, Categorical

Age Continuous

Sex: Female, Male

United States

Region of Enrollment

Overall Response Rate

Overall Survival

Time to Progression

Cell Surface Expression of CD52 on Tumor Cells

The Number of Participants With Adverse Events

Overall Study

Lymphoma, Large-Cell, Anaplastic

Anaplastic Large Cell Lymphoma

Immunologic Factors

HeFi-1 Monoclonal Antibody

Background:

* Some cancers, such as Hodgkin's disease, anaplastic large cell lymphoma and others, have a protein on the surface of the cancer cell called CD30.
* HeFi-1 is an antibody that binds to the CD30 protein and sends signals to the cancer cells that can cause them to die.

Objectives:

* To determine the highest dose of HeFi-1 that can safely be given to patients with tumors that have the CD30 protein.
* To determine the response of the tumor to treatment with HeFi-1.

Eligibility:

* Patients 18 years of age and older with Hodgkin's disease, anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia or lymphoma who have signs of tumor growth or recurrence following standard treatment
* Patients' tumor cells must have the CD30 protein.

Design:

* Groups of three patients are treated with increasingly higher doses of HeFi-1 (ranging from 0.5 to 5 mg/kg) to determine the highest safe dose.
* HeFi-1 is infused through a vein on 4 days, followed by 2 days of rest over a 10-day period. Patients may receive up to 2 treatment courses if they show some response and do not have severe side effects.
* Blood samples are collected several times during the study to determine safety. A lymph node biopsy is done at the beginning of the study to test the effect of HeFi-1 on cancer cells in the test tube, and a bone marrow biopsy may be done at the end of treatment if the bone marrow was positive for tumor cells at the beginning of treatment.

BACKGROUND:

The scientific basis for this study is the observation that antibodies directed at the ligand-binding site of CD30 induce apoptosis in vitro and cure animals bearing CD30-positive tumors.

HeFi-1, a murine monoclonal antibody developed at the NCI, specifically binds human CD30, a member of the tumor necrosis receptor superfamily, at the ligand-binding site.

CD30 is expressed on activated T-cells, Reed-Sternberg cells, anaplastic large cell lymphoma, and some AIDS-related lymphoma cells.

Tumor cells from patients with anaplastic large cell lymphoma are sensitive to the effects of HeFi-1 but Hodgkin's disease cell lines show variable responsiveness due to the presence of mutations in I B kinase which result in constitutive activation of NF- B.

OBJECTIVE:

The primary objective of this study is to determine the toxicity and maximum tolerated dose of HeFi-1 in patients with CD30-positive malignancy.

This study will explore the pharmacokinetics, dose required to saturate CD30 binding sites in tumor aspirates, and the frequency and time course of onset of development of human anti-mouse antibody (HAMA).

These studies will allow us to monitor in a preliminary fashion the clinical tumor response, measured by reduction in tumor lesions and by following the tumor marker serum soluble interleukin 2 receptor.

ELIGIBILITY:

Patients with measurable or evaluable CD30-positive lymphoma who have become refractory to standard therapy, including Hodgkin's disease, systemic anaplastic large cell lymphoma, cutaneous T cell lymphoma and adult T cell leukemia/lymphoma are eligible for treatment.

DESIGN:

This is a phase I dose-escalation trial in which cohorts of three patients will be treated with HeFi-1 ranging from 0.5 to 5 mg/kg/dose (total dose of 2 to 20 mg/kg per treatment course).

Four doses will be given on an every three days schedule over a 10-day period for each cycle.

Two cycles of therapy will be administered provided the patient has had a partial or complete response and has not developed dose-limiting toxicity or HAMA.

Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein

Phase I Study of HeFi-1 in Refractory CD30-Positive Malignancy

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Campath-1H for Treating Adult T-Cell Leukemia/Lymphoma	NCT00061048	Acute T-Cell Le...	Alemtuzumab	18 Years -	National Institutes of Health Clinical Center (CC)
Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein	NCT00048880	Neoplasms	HeFi-1 Monoclon...	18 Years -	National Institutes of Health Clinical Center (CC)
Phase I Study of HeFi-1 to Treat Cancers With CD30 Protein	NCT00048880	Neoplasms	HeFi-1 Monoclon...	18 Years -	National Institutes of Health Clinical Center (CC)

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