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
- Conditions
- Diffuse Large B-Cell LymphomaHodgkin Lymphoma
- Interventions
- Biological: CampathBiological: RituximabDrug: EPOCH
- Registration Number
- NCT01030900
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief 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.
- Detailed 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath Campath Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin (EPOCH) + Rituximab + campath every 3 weeks for six cycles Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath Rituximab Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin (EPOCH) + Rituximab + campath every 3 weeks for six cycles Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin + Rituximab + Campath EPOCH Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin (EPOCH) + Rituximab + campath every 3 weeks for six cycles
- Primary Outcome Measures
Name Time Method Progression Free Survival (PFS) Time of progression or death, approximately 10 months PFS is the time interval from start of treatment to documented evidence of disease progression estimated using a Kaplan Meier curve. Progression was assessed by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphomas and is defined as ≥50% increase from nadir in the sum of the products of diameters of any previously identified abnormal node for partial response or non-responders. And an appearance of any new lesion during or at the end of therapy.
Overall Survival (OS) Median overall survival from enrollment to the day of death, approximately 17.9 months OS is from enrollment to the day of death estimated using the Kaplan-Meier curve.
- Secondary Outcome Measures
Name Time Method Clinical Response on Study and at Relapse After Dose Adjusted - Etoposide + Prednisone + Vincristine + Cyclophosphamide + Doxorubicin + Rituximab (DA-EPOCH-RC) On study and at relapse after study treatment, approximately 10 months Clinical response was assessed by the International Workshop to Standardize Response Criteria for non-Hodgkin's Lymphomas. Complete remission is complete disappearance of all detectable clinical and radiographic evidence of disease. Complete response unconfirmed is as per complete remission except that if a residual node is greater than 1.5cm, it must have decreased by greater than 75% in the sum of the products of the perpendicular diameters (SPD). Partial response is ≥50% decreased in the SPD of 6 largest dominant nodes or nodal masses. Relapsed disease is appearance of any new lesion or increase by ≥50% in the size of the previously involved sites. Stable disease is defined as less than a partial response but not progressive disease. Progression is ≥50% increase from nadir in the SPD of diameters of any previously identified abnormal node for partial response or non-responders; and an appearance of any new lesion during or at the end of therapy.
Trial Locations
- Locations (1)
National Institutes of Health Clinical Center, 9000 Rockville Pike
🇺🇸Bethesda, Maryland, United States