Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01030900 |
Other study ID # |
100011 |
Secondary ID |
10-C-0011 |
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
October 22, 2009 |
Est. completion date |
August 6, 2021 |
Study information
Verified date |
September 2022 |
Source |
National Institutes of Health Clinical Center (CC) |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
Background:
- Studies conducted at the National Cancer Institute suggest that certain chemotherapy
drugs may be more effective if given by continuous infusion into the vein rather than by
the standard method of rapid intravenous injection. One combination of six chemotherapy
drugs, known as etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and
rituximab (EPOCH-R), has had a high degree of effectiveness in people with certain kinds
of cancer.
- Recent evidence also indicates that the effects of chemotherapy may be improved by
combining the treatment with monoclonal antibodies, which are purified proteins that are
specially made to attach to foreign substances such as cancer cells. A monoclonal
antibody called campath (alemtuzumab) has been manufactured to attach to a protein
called Campath-1 antigen (CD52) that may target tumor cells or the surrounding
inflammatory cells.
- Researchers are interested in developing new treatments for large B-cell lymphoma or
Hodgkin lymphoma that can best be treated with chemotherapy. This protocol is
specifically for people with diffuse large B-cell or Hodgkin lymphomas that have not
responded to standard treatments.
Objectives:
- To test whether giving campath (alemtuzumab) in combination with continuous infusion
EPOCH-R chemotherapy will improve the outcome of lymphoma treatment.
Eligibility:
- Individuals 18 years of age and older who have large B-cell lymphoma or Hodgkin lymphoma
that has not responded well to standard treatments.
Design:
- During the study, patients will receive standard EPOCH-R chemotherapy, which includes
the following drugs: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin,
and rituximab. The additional drug, campath, will be given by intravenous (IV) infusion
on the first day of treatment over several hours.
- When the campath IV infusion and rituximab IV infusion are complete, the drugs
doxorubicin, etoposide, and vincristine will each be given by continuous IV infusion
over the next 4 days (that is, continuously for a total of 96 hours). Cyclophosphamide
will be given by IV infusion over several hours on Day 5. Prednisone will be given by
mouth twice each day for 5 days.
- Patients may be given other drugs to treat the side effects of chemotherapy, to prevent
possible infections, and to improve white blood cell counts.
- The campath-EPOCH-R therapy will be repeated every 21 days, as a cycle of therapy, for a
total of 6 cycles. Following the fourth and sixth treatment cycles (approximately weeks
12 and 18) of campath-EPOCH-R treatment, study researchers will perform blood tests and
computed tomography (CT)/magnetic resonance imaging (MRI) scans on all patients to
assess their response to the treatment.
Description:
Background:
Two signatures of the microenvironment were recently identified that are predictive of
outcome in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL), treated with
rituximab, cyclophosphamide, hydroxydaunorubicin hydrochloride (doxorubicin hydrochloride),
vincristine (Oncovin) and prednisone (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.
- Campath-1 antigen (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 dose-adjusted etoposide, prednisone,
vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH) is 30 mg
intravenous (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.
Eligibility:
- Previously treated or refractory 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.
- Human immunodeficiency virus (HIV) negative and no active central nervous system (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 52 patients is expected to require approximately 4-5 years.