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
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|ClinicalTrials.gov Identifier: NCT01030900|
Recruitment Status : Active, not recruiting
First Posted : December 14, 2009
Last Update Posted : January 13, 2020
- 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.
- To test whether giving campath (alemtuzumab) in combination with continuous infusion EPOCH-R chemotherapy will improve the outcome of lymphoma treatment.
- Individuals 18 years of age and older who have large B-cell lymphoma or Hodgkin lymphoma that has not responded well to standard treatments.
- 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.
|Condition or disease||Intervention/treatment||Phase|
|Hodgkin Lymphoma Diffuse Large B-Cell Lymphoma||Biological: campath Biological: Rituximab Drug: EPOCH||Phase 2|
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.
- Assess response, progression free survival (PFS) and overall survival (OS) in relapsed/refractory DLBCL and Hodgkin Lymphoma.
- 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.
- 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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||50 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||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|
|Study Start Date :||October 22, 2009|
|Estimated Primary Completion Date :||September 1, 2021|
|Estimated Study Completion Date :||September 1, 2021|
EPOCH + Rituximab + campath every 3 weeks for six cycles
campath plus EPOCH and rituximab every 3 weeks for up to 6 cycles
rituximab plus EPOCH and campath every 3 weeks for up to 6 cycles
EPOCH plus rituximab and campath every 3 weeks for up to 6 cycles
- PFS and OS [ Time Frame: Time of progression and time of death ]Two-stage Simon optimal design (Simon R, Controlled Clinical Trials, 10:1-10, 1989) in order to rule out an unacceptably low 25% clinical response rate (PR+CR: p0=0. 25) in favor of a targeted rate consistent with 45% (p1=0.45)
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01030900
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Wyndham H Wilson, M.D.||National Cancer Institute (NCI)|