This study will examine the safety and effectiveness of combination therapy with the monoclonal antibody Campath-1H and continuous infusion of a chemotherapy regimen called EPOCH for treating non-Hodgkin's T-cell and NK-cell lymphomas. In general, T-cell and NK-cell lymphomas are less responsive to standard treatments than B-cell lymphomas. EPOCH, which includes the drugs doxorubicin, etoposide, vincristine, cyclophosphamide, and prednisone, has shown a high degree of effectiveness in patients whose tumors have stopped responding to standard regimens. Campath-1H may improve the effects of chemotherapy.

Patients 17 years of age and older with T- or NK-cell non-Hodgkin's lymphoma who are newly diagnosed, have not received chemotherapy and whose disease is considered to be more amenable to chemotherapy than surgery or radiation may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood and urine tests, and electrocardiogram. Other tests that may be required include: lumbar puncture (spinal tap); imaging tests such as magnetic resonance imaging (MRI), positron emission tomography (PET), computed tomography (CT), and X-rays; and biopsy (surgical removal of a small tissue sample) of tumor, bone marrow, or other tissue.

Patients receive treatment in chemotherapy cycles that are repeated every 3 weeks. Drugs are administered during the first 5 days of the cycle, followed by 16 days of rest. The treatment is repeated for 6 to 8 cycles depending on tumor response to therapy:

Campath-1H, given by vein over about 12 hours on the first day of therapy, immediately before the chemotherapy infusion begins.

Doxorubicin, etoposide, and vincristine, given by continuous IV infusion over 4 days, beginning on day 1 and ending on day 5 of each cycle. The drugs are delivered through a lightweight portable infusion pump to an indwelling IV catheter (plastic tube) in a vein.

Cyclophosphamide, given by IV infusion over 15 minutes on day 5 of each cycle.

Prednisone, given by mouth (pills) twice a day on days 1 through 5 of each cycle.

Filgrastim, given by injection under the skin once a day starting on day 6 of each cycle and continuing until recovery of the white blood cell count or until day 19 of the cycle. This drug helps normal bone marrow cells recover from the chemotherapy and produce white blood cells called neutrophils.

Patients also take a combination of antibiotics 3 days a week during EPOCH to prevent infection while resistance is lowered because of the chemotherapy

Patients who show no signs of disease at the end of treatment will be seen periodically at the Clinical Center for follow-up tests and examinations. Patients whose disease does not disappear entirely, gets worse, or recurs after having disappeared will be offered participation in other appropriate research protocols, if available, or will be returned to the care of the referring physician.

Condition	Treatment or Intervention	Phase
Lymphoma	Procedure: Electrocardiogram  Procedure: Urine tests  Procedure: Blood Tests  Procedure: MRI	Phase II

Further Study Details: 

Expected Total Enrollment:  24

The paradigm of combining therapeutic agents with non-overlapping toxicities for the treatment of malignancy produces clinical remissions and cures in a number of tumor types. A new class of agents, humanized and chimerized monoclonal antibodies, typically have little or no hematopoietic toxicity and can be readily combined with full doses of cytotoxic chemotherapy. It has become clear that in certain lymphomas and breast cancers, the combination of monoclonal antibodies and chemotherapy improves response rate and the quality of the response compared with that achieved by treatment with either agent alone. The clinical outcome for patients with T cell non-Hodgkin's lymphoma is significantly inferior to the outcome of patients with B-cell non-Hodgkin's lymphoma. In most reports less than 20% of patients with T cell lymphoid malignancies remain free of disease at 5 years. Although EPOCH chemotherapy appears to improve outcome in patients with B-cell lymphoid malignancy, it does not improve the outcome for those with T-cell malignancy. In this study we plan to investigate the safety and in a preliminary fashion the antitumor activity of Alemtuzumab and EPOCH infusional chemotherapy in patients with non B-cell CD52-expressing lymphoid malignancies. The purpose of this trial is to establish a dose of Alemtuzumab for evaluation in Phase II trials in specific CD52-expressing malignancies.

Genders Eligible for Study:  Both

Criteria

ELIGIBILTY CRITERIA:
CD52-expressing lymphoid malignancy, confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, NCI. Patients with T & NK cell malignancy without accessible tissue for flow cytometry analysis may be treated on this study.
Patients with chemotherapy naive aggressive T & NK lymphomas, including but not limited to peripheral T cell lymphoma (nos), gamma-delta hepatosplenic T cell lymphoma, subcutaneous panniculitis-like T cell, NK-T cell lymphoma confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, NCI. Patients with alk-positive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.
Age greater than or equal to 17 years.
Laboratory tests: Creatinine less than or equal to 1.5 mg/dL or creatinine clearance greater than or equal to 60 ml/min; bilirubin less than 2.0 mg/dl unless due to Gilbert's, AST and ALT less than or equal to 3x ULN (AST and ALT is less than or equal to 6x ULN for patients on hyperalimentation) and; ANC is greater than or equal to 1000/mm(3), platelet greater than or equal to 75,000/mm(3); unless impairment due to respective organ involvement by tumor.
No active symptomatic ischemic heart disease, myocardial infarction or congestive heart failure within the past year.
HIV negative, because of the unknown effects of combined therapy with chemotherapy and an immunosuppressive agent on HIV progression.
Signed informed consent.
Willing to use contraception.
Not pregnant or nursing, because of the unknown effects of Alemtuzumab on the developing fetus and infant.
No serious underlying medical condition or infection that would contraindicate treatment. Patients with CNS involvement are eligible for treatment on this study.

Maryland
      National Cancer Institute (NCI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  030304; 03-C-0304
Record last reviewed:  August 18, 2004
Last Updated:  November 23, 2004
Record first received:  September 17, 2003
ClinicalTrials.gov Identifier:  NCT00069238
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08