Trial Information

Pilot Trial of Alemtuzumab and Dose-Adjusted Epoch in Chemotherapy Naive Aggressive T and NK-Cell Lymphomas

Background:

The paradigm of combining therapeutic agents with non-overlapping toxicities for the
treatment of malignancy produces clinical remissions and cures in a number of tumor types.

A new class of agents, humanized and chimerized monoclonal antibodies, typically have little
or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic
chemotherapy. It has become clear that in certain lymphomas and breast cancers, the
combination of monoclonal antibodies and chemotherapy improves response rate and the quality
of the response compared with that achieved by treatment with either agent alone.

The clinical outcome for patients with T-cell non-Hodgkin's lymphoma is significantly
inferior to the outcome of patients with B-cell non-Hodgkin's lymphoma. In most reports less
than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years.

Objectives:

Determine the toxicity of Alemtuzumab and EPOCH chemotherapy in untreated CD52-expressing T
and NK lymphoid malignancies.

Determine the maximum tolerated dose of Alemtuzumab administered in combination with EPOCH
chemotherapy.

Determine in a preliminary fashion the anti-tumor activity of the combination of Alemtuzumab
and EPOCH chemotherapy.

Eligibility:

CD52-expressing lymphoid malignancy.

Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alk-positive
anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Age greater than or equal to 17 years.

Adequate organ function, unless impairment due to respective organ involvement by tumor.

No active symptomatic ischemic heart disease, myocardial infarction or congestive heart.
failure within the past year.

HIV negative.

Not pregnant or nursing.

Design:

Three dose levels of Alemtuzumab will be evaluated to determine the toxicity profile and in
a preliminary fashion the antitumor activity of the combination with Dose-Adjusted EPOCH.

Three dose levels of Alemtuzumab will be explored, in cohorts of three to six patients each.
Patients will receive either 30, 60, or 90 mg of Alemtuzumab on day 1 of therapy, followed
by dose-adjusted EPOCH chemotherapy days 1-5.