Trial Information

Phase II Trial of Alemtuzumab (Campath) and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in Relapsed or Refractory Diffuse Large B-Cell and Hodgkin Lymphomas

Background:

Two signatures of the microenvironment were recently identified that are predictive of
outcome in patients with newly diagnosed DLBCL treated with R-CHOP. These signatures, called
stromal 1' and stromal 2', are associated with genes expressed by infiltrating mononuclear
cells. The stromal 2 signature, which includes genes associated with angiogenesis, is
predictive of an inferior outcome. Based on these observations, we are interested in
targeting the reactive cells in the microenvironment as a therapeutic strategy in patients
with relapsed and refractory DLBCL. Along the same principles, we are also including
patients with relapsed Hodgkin lymphoma (HL). The surrounding reactive cells around Hodgkin
Reed Sternberg (HRS) cells are now not thought to be bystander cells and they appear to
provide important survival signals to HRS cells.

- CD52 is one such promising target that is highly expressed in most of these
infiltrating cells and on most DLBCL although not on HRS cells specifically. Anti-CD52
antibodies may have therapeutic value by depleting reactive B and T cells, and
monocytes from the microenvironment.

- The dose of alemtuzumab in combination with DA-EPOCH is 30 mg IV, as determined by a
prior study done in patients with untreated peripheral T-cell lymphoma. The main
toxicities of this combination are myelosuppression and opportunistic infections.

- An important component of this study will be to obtain tumor tissue for gene expression
profiling and to assess microenvironment signatures and look at other molecular
signatures and targets before treatment and in patients who progress and ultimately
correlate response and outcome with these various end-points.

Objectives:

- Assess response, progression free survival (PFS) and overall survival (OS) in
relapsed/refractory DLBCL and Hodgkin Lymphoma.

- Correlate outcome with gene expression profiling and immunohistochemistry of tumor
tissue (in particular looking at microenvironment/stromal molecular signatures).

Eligibility:

- Previously treated orrefractory classical large B-cell lymphomas, Grey-zone lymphoma
and Hodgkin lymphoma, including Lymphocyte predominant Hodgkin Lymphoma (LPHL).

- Age greater than or equal to 18 years with adequate organ functions.

- HIV negative and no active CNS lymphoma.

Study Design:

- Patients will receive 30mg of Alemtuzumab on day 1 of therapy, followed by Rituximab on
day 1 and dose-adjusted EPOCH chemotherapy days 1-5, up to six cycles of therapy.

- Tumor biopsies will be done before treatment, after 1 cycle of therapy and at relapse.

- It is anticipated that up to 10-15 patients per year may be enrolled onto this trial.
Thus, accrual of up to 44 evaluable patients is expected to require approximately 3-4
years.