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

NCT ID: NCT00061048

Last Updated: 2012-10-31

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2003-05-31

Study Completion Date

2012-07-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Acute T-Cell Leukemia-Lymphoma

Keywords

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Monoclonal Antibody HTLV-1 CD52 Flow Cytometry Antibody Saturation Adult T-Cell Leukemia (ATL) ATL

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Campath-1H

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.

Group Type EXPERIMENTAL

Alemtuzumab

Intervention Type BIOLOGICAL

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.

Interventions

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Alemtuzumab

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.

Intervention Type BIOLOGICAL

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Cancer Institute (NCI)

NIH

Sponsor Role lead

Responsible Party

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National Cancer Institute, National Institutes of Health

Principal Investigators

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Thomas A Waldmann, M.D.

Role: PRINCIPAL_INVESTIGATOR

NCI, NIH

Locations

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National Institutes of Health, National Cancer Institute

Bethesda, Maryland, United States

Site Status

Countries

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United States

References

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Kohler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. 1975. Biotechnology. 1992;24:524-6. No abstract available.

Reference Type BACKGROUND
PMID: 1422065 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 3060441 (View on PubMed)

Dickman S. Antibodies stage a comeback in cancer treatment. Science. 1998 May 22;280(5367):1196-7. doi: 10.1126/science.280.5367.1196. No abstract available.

Reference Type BACKGROUND
PMID: 9634400 (View on PubMed)

Chen J, Pise-Masison CA, Shih JH, Morris JC, Janik JE, Conlon KC, Keating A, Waldmann TA. Markedly additive antitumor activity with the combination of a selective survivin suppressant YM155 and alemtuzumab in adult T-cell leukemia. Blood. 2013 Mar 14;121(11):2029-37. doi: 10.1182/blood-2012-05-427773. Epub 2013 Jan 15.

Reference Type DERIVED
PMID: 23321252 (View on PubMed)

Related Links

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Other Identifiers

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03-C-0194

Identifier Type: OTHER

Identifier Source: secondary_id

030194

Identifier Type: OTHER

Identifier Source: secondary_id

030194

Identifier Type: -

Identifier Source: org_study_id

NCT00064155

Identifier Type: -

Identifier Source: nct_alias