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: Completed
• Trial end date: 2021-08-06
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Alemtuzumab; Rituximab

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.