Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in T and NK-Cell Lymphomas
18 Years
N/A
Both
T-Cell Peripheral Lymphoma, Gamma Delta Hepatosplenic T-Cell Lymphoma, Subcutaneous Panniculitis-Like T-Cell Lymphoma, NK T-Cell Lymphoma
Trial Information
Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in T and NK-Cell Lymphomas
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 naive 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.
Inclusion 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 3 times ULN (AST and ALT less than or equal to 6 times 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/mm(3), platelet greater than or
equal to 75,000/mm(3); unless impairment due to respective organ impairment 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.
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Determine the toxicity of siplizumab and DA-EPOCH-R in chemotherapy na ve CD2-expressing T and NK lymphoid malignancies.Determine the maximum tolerated dose of siplizumab administered in combination with DA-EPOCH-R.
Principal Investigator
Wyndham H Wilson, M.D.
Investigator Role:
Principal Investigator
Investigator Affiliation:
National Cancer Institute (NCI)
Authority:
United States: Federal Government
Study ID:
090065
NCT ID:
NCT01445535
Start Date:
January 2009
Completion Date:
Related Keywords:
- T-Cell Peripheral Lymphoma
- Gamma Delta Hepatosplenic T-Cell Lymphoma
- Subcutaneous Panniculitis-Like T-Cell Lymphoma
- NK T-Cell Lymphoma
- CD2 Positive
- Toxicity
- EBV Lymphoma
- Chemotherapy Naive
- Maximum Tolerated Dose
- Lymphoma
- T-Cell Lymphoma
- NK T-Cell Lymphoma
- Lymphoma
- Panniculitis
- Lymphoma, T-Cell
Name | Location |
|---|---|
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland 20892 |
