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
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Lymphoma |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | 18 - 100 |
| Updated: | 2/24/2019 |
| Start Date: | October 22, 2009 |
| End Date: | September 1, 2020 |
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 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 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 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
CT/MRI scans on all patients to assess their response to the treatment.
- 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 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 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 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
CT/MRI scans on all patients to assess their response to the treatment.
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.
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 52 patients is expected to require approximately 4-5 years.
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.
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 52 patients is expected to require approximately 4-5 years.
- 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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
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