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

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT01030900
First received: December 11, 2009
Last updated: September 5, 2014
Last verified: February 2014
  Purpose

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.

Condition Intervention Phase
Hodgkin Lymphoma
Diffuse Large B-Cell Lymphoma
Drug: Cylcophosphamide
Drug: Etoposide
Drug: Alemtuzumab
Drug: Doxorubicin
Drug: Prednisone
Drug: Filgrastim
Drug: Rituximab
Drug: Vincristine
Phase 2

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

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Assess response, progression free survival (PFS) and overall survival (OS) in relapsed/refractory DLBCL and Hodgkin lymphoma. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Correlate clinical outcomes with microenvironment/stromal molecular signatures by gene expression profiling and immunohistochemistry on study and at relapse after DA-EPOCH-RC. [ Time Frame: 5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 52
Study Start Date: October 2009
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Group 1 Drug: Cylcophosphamide
750 mg/m2 day 5 each cycle
Drug: Etoposide
50 mg/m2 days 1-4 each cycle
Drug: Alemtuzumab
30 mg day 1 each cycle
Drug: Doxorubicin
10 mg/m2/day days 1-4 each cycle
Drug: Prednisone
60 mg/m2 BID days 1-5 each cycle
Drug: Filgrastim
480 mcg/day for approx. 10 days each cycle
Drug: Rituximab
375 mg/m2 day 1 each cycle
Drug: Vincristine
0.4 mg/m2/day days 1-4 each cycle

Detailed Description:

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 52 patients is expected to require approximately 4-5 years.
  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01030900

Contacts
Contact: Margaret Shovlin, R.N. (301) 594-6597 mshovlin@mail.nih.gov
Contact: Wyndham H Wilson, M.D. (301) 435-2415 wilsonw@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    (888) NCI-1937      
Sponsors and Collaborators
Investigators
Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:

Responsible Party: National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier: NCT01030900     History of Changes
Other Study ID Numbers: 100011, 10-C-0011
Study First Received: December 11, 2009
Last Updated: September 5, 2014
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Immunosuppression
Microenvironment
Hodgkin Lymphoma
B-Cell Lymphoma
Microarray
Diffuse Large B-Cell Lymphoma

Additional relevant MeSH terms:
Lymphoma, B-Cell
Lymphoma, Large B-Cell, Diffuse
Hodgkin Disease
Lymphoma
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
Immune System Diseases
Rituximab
Alemtuzumab
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 16, 2014