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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Hodgkin Lymphoma, Diffuse Large B-Cell Lymphoma

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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.

Inclusion Criteria


- INCLUSION CRITERIA:

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

2. Confirmed pathological diagnosis by the Laboratory of Pathology, NCI.

3. Age greater than or equal to 18 years.

4. ECOG performance 0-2

5. Laboratory tests: ANC greater than or equal to 1000/mm(3), platelet greater than
or equal to 75,000/mm(3). Creatinine less than or equal to 1.5 mg/dL or
creatinine clearance greater than or equal to 60 ml/min; AST and ALT less than
or equal to 5 times the ULN. Total bilirubin < 2.0 mg/dl except < 5mg/dL in
patients with Gilbert's (as defined as > 80% unconjugated hyperbilirubinemia
without other known cause); unless impairment due to organ involvement by
lymphoma.

EXCLUSION CRITERIA:

1. Active symptomatic ischemic heart disease, myocardial infarction or congestive heart
failure within the past year. If ECHO is obtained, the LVEF should exceed 40%.

2. HIV positive, because of the unknown effects of combined therapy with chemotherapy
and an immunosuppressive agent on HIV progression.

3. Female subject of child-bearing potential not willing to use an acceptable method of
birth control (i.e. a hormonal contraceptive, intrauterine device, diaphragm with
spermicide, condom with spermicide, or abstinence) for the duration of the study and
two years beyond treatment completion.

4. Female subject pregnant or breast-feeding. Confirmation that the subject is not
pregnant must be established by a negative serum beta-human chorionic gonadotrophin
(beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not
required for women without childbearing potential.

5. Male subject unwilling to use an acceptable method for contraception for the duration
of the study and one year beyond treatment completion.

6. Invasive or active malignancy in past 2 years.

7. Serious concomitant medical illnesses that would jeopardize the patient's ability to
receive the regimen with reasonable safety.

8. Active CNS lymphoma. These patient have a poor prognosis and because they frequently
develop progressive neurological dysfunction that would confound the evaluation of
neurological and other adverse events.

9. Systemic cytotoxic therapy within 3 weeks of treatment.

Type of Study:

Interventional

Study Design:

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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

Outcome Time Frame:

5 years

Safety Issue:

No

Principal Investigator

Wyndham H Wilson, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Cancer Institute (NCI)

Authority:

United States: Federal Government

Study ID:

100011

NCT ID:

NCT01030900

Start Date:

October 2009

Completion Date:

September 2014

Related Keywords:

  • Hodgkin Lymphoma
  • Diffuse Large B-Cell Lymphoma
  • Immunosuppression
  • Microenvironment
  • Hodgkin Lymphoma
  • B-Cell Lymphoma
  • Microarray
  • Diffuse Large B-Cell Lymphoma
  • Hodgkin Disease
  • Lymphoma
  • Lymphoma, B-Cell
  • Lymphoma, Large B-Cell, Diffuse

Name

Location

National Institutes of Health Clinical Center, 9000 Rockville PikeBethesda, Maryland  20892