Protocol Number: 09-C-0065

Title:

Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in T and NK-Cell Lymphomas

Number:

09-C-0065

Summary:

Background:

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.

The combination of alemtuzumab and EPOCH chemotherapy was evaluated in patients with chemotherapy naive aggressive T and NK cell lymphoid malignancy. Dose-limiting bone marrow toxicity prevented escalation of the alemtuzumab dose.

Siplizumab is a humanized monoclonal antibody directed at CD2 that demonstrated activity in the treatment of relapsed/refractory T cell lymphoma, suggesting further development by combining with chemotherapy for untreated patients. Siplizumab caused EBV lymphoproliferative disease in patients treated with a weekly schedule of administration.

Rituximab prevents the development of EBV lymphoproliferative disease in the allogeneic transplant setting and may be active in preventing EBV-related B cell lymphoma in other settings.

Objectives:

Determine the toxicity of siplizumab and dose-adjusted EPOCH rituximab chemotherapy in chemotherapy na ve CD2-expressing T and NK lymphoid malignancies.

Determine the maximum tolerated dose of siplizumab administered in combination with dose-adjusted EPOCH rituximab chemotherapy.

Eligibility:

CD2-expressing lymphoid malignancy.

Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alkpositive anaplastic large cell lymphoma and patients with T cell precursor disease are not eligible.

Design:

Four dose levels of siplizumab will be evaluated to determine the toxicity profile and in a preliminary fashion and its activity in combination with dose-adjusted EPOCH with rituximab.

Four dose levels of siplizumab will be explored, in cohorts of three to six patients each. Patients will receive 3.4, 4.8, 8.5, or 15 mg/kg of siplizumab on day 1 of therapy, followed by dose-adjusted EPOCH-rituximab chemotherapy days 1-5 every 3 weeks for a total of 6 cycles.

Sponsoring Institute:

National Cancer Institute (NCI)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

Eligibility Criteria:

INCLUSION CRITERIA:

CD2-expressing lymphoid malignancy, confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, NCI. At least 30% of the malignant cells must be CD2 positive for inclusion in this study.

Patients with chemotherapy naive 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 18 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 (unconjugated hyperbilirubinemia without other known cause), AST and ALT less than or equal to 3x ULN (AST and ALT less than or equal to 6x ULN for patients on hyperalimentation for whom these abnormalities are felt to be due to the hyperalimentation) and; ANC greater than or equal to 1000/mm3, platelet greater than or equal to 75,000/mm3; 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 by the patient or patient's representative.

Willing to use contraception.

Not pregnant or nursing, because of the unknown effects of DA-EPOCH-R or siplizumab 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.

EXCLUSION CRITERIA:

Patients less than 18 years of age will be excluded because siplizumab has not been given to minors in combination with chemotherapy.

Special Instructions:

Currently Not Provided

Keywords:

CD2 Positive

Toxicity

EBV Lymphoma

Chemotherpay Naive

Maximum Tolerated Dose

Recruitment Keyword(s):

None

Condition(s):

T-Cell Peripheral Lymphoma

Gamma Delta Hepatosplenic T-Cell Lymphoma

Subcutaneous Panniculitis-Like T-Cell Lymphoma

NK T-Cell Lymphoma

Investigational Drug(s):

Siplizumab (Medi-507)

Investigational Device(s):

None

Intervention(s):

Drug: Siplizumab (Medi-507)

Drug: Etoposide

Drug: Cyclophosphamide

Drug: Doxorubicin

Drug: Vincristine

Drug: Prednisone

Drug: Rituximab

:

Supporting Site:

National Cancer Institute

Contact(s):

NCI Referral Office
National Institute of Health Clinical Center (CC), 9000 Rockville Pike, Bethesda, Maryland 20892, United States: NCI Clinical Trials Referral Office
Phone: 1-888-NCI-1937
Fax: Not Listed
Electronic Address: ncicssc@mail.nih.gov

Citation(s):

Abruzzo LV, Rosales CM, Medeiros LJ, Vega F, Luthra R, Manning JT, Keating MJ, Jones D. Epstein-Barr virus-positive B-cell lymphoproliferative disorders arising in immunodeficient patients previously treated with fludarabine for low-grade B-cell neoplasms. Am J Surg Pathol. 2002 May;26(5):630-6.

Bhargava R, Barbashina V, Filippa DA, Teruya-Feldstein J. Epstein-Barr virus positive large B-cell lymphoma arising in a patient previously treated with Cladribine for hairy cell leukemia. Leuk Lymphoma. 2004 May;45(5):1043-8.

Birkeland SA, Hamilton-Dutoit S. Is posttransplant lymphoproliferative disorder (PTLD) caused by any specific immunosuppressive drug or by the transplantation per se? Transplantation. 2003 Sep 27;76(6):984-8.

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