Clinical trial · Interventional
Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas
Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in T and NK-Cell Lymphomas
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
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 such combination of six chemotherapy drugs, known as Etoposide, Prednisone, Vincristine, Cyclophosphamide, Doxorubicin, Rituximab (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. This protocol is specifically for adults with the types of cancer known as T-cell and Naturel Killer (NK)-cell lymphomas, who have never received chemotherapy previously. The additional monoclonal antibody in the study, called siplizumab, has been manufactured to attach to the cluster of differentiation 2 (CD2) protein contained in these types of tumors. Study volunteers will need to undergo an initial period of evaluation that may take up to 3 weeks and may be done on an outpatient basis. Evaluation may include some or all of the following tests: blood and urine tests, tests of lung and heart function, lumbar punctures to take samples of cerebrospinal fluid, magnetic resonance imaging (MRI) or computerized tomography (CT) scans, full-body positron emission tomography (PET) scans, bone marrow biopsies, and biopsies of suspected tumor areas. During the study, patients will receive EPOCH-R chemotherapy, which includes the following drugs: etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab. The additional drug, siplizumab, will be given by IV infusion on the first day of treatment over several hours. When the siplizumab intravenous (IV) infusion is 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). When this infusion is completed, the drugs rituximab and 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 and to prevent possible infections. The siplizumab-EPOCH-R therapy will be repeated every 21 days, which is known as a cycle of therapy, for a total of 6 cycles. Following the fourth and sixth treatment cycles (approximately weeks 12 and 18) of siplizumab-EPOCH-R, study researchers will perform blood tests and CT/MRI scans on all patients to assess their response to the treatment.
Conditions
Conditions (4)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Gamma Delta Hepatosplenic T-Cell Lymphoma | — | UNRESOLVED | — |
| NK T-Cell Lymphoma | — | UNRESOLVED | — |
| Subcutaneous Panniculitis-Like T-Cell Lymphoma | Subcutaneous Panniculitis-Like T-Cell Lymphoma | ONTOLOGY_EXACT | 0.98 |
| T-Cell Peripheral Lymphoma | — | UNRESOLVED | — |
Interventions
Interventions (7)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Cyclophosphamide | Drug | Cyclophosphamide | ALIAS |
| Doxorubicin | Drug | Doxorubicin | ALIAS |
| Etoposide | Drug | Etoposide | ALIAS |
| Prednisone | Drug | Prednisone | ALIAS |
| Rituximab | Biological | Rituximab | ALIAS |
| Siplizumab | Biological | — | UNRESOLVED |
| Vincristine | Drug | Vincristine | ALIAS |
Design
Arms and outcomes
Arms (1)
- type
- EXPERIMENTAL
- label
- siplizumab + EPOCH (combo chemo) + rituximab
- description
- siplizumab will be given with EPOCH (combo chemo) and rituximab every 21 days
- interventionNames
- Biological: Rituximab
- Drug: Etoposide
- Biological: Siplizumab
- Drug: Prednisone
- Drug: Vincristine
- Drug: Cyclophosphamide
- Drug: Doxorubicin
Primary outcomes (2)
- measure
- Number of Participants With Serious and Non-serious Adverse Events
- timeFrame
- Date treatment consent signed until 30 days after removal from study treatment or until off study, whichever comes first, approximately 22 weeks.
- description
- Here is the count of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.
Eligibility
Eligibility (as posted)
- Sex
- All
- Minimum age
- 18 Years
- Maximum age
- 120 Years
Show eligibility criteria text
* INCLUSION CRITERIA: Cluster of differentiation 2 (CD2)-expressing lymphoid malignancy, confirmed by pathology or flow cytometry staff of the Hematopathology Section, Laboratory of Pathology, National Cancer Institute (NCI). At least 30% of the malignant cells must be CD2 positive for inclusion in this study. Patients with chemotherapy naive T \& Natural Killer (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), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) less than or equal to 3 times upper limit of normal (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; Absolute neutrophil count (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. Patients must not have a marked baseline prolongation of Q wave, T wave (QT/QTc) interval (e.g., demonstration of a corrected QT interval (QTc) interval \>500 milliseconds (ms)). Human immunodeficiency virus (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 dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab (DA-EPOCH-R) or siplizumab on the developing fetus and infant. No serious underlying medical condition or infection that would contraindicate treatment. Patients with central nervous system (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.
References
Publications (4)
- BACKGROUNDAbruzzo 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. doi: 10.1097/00000478-200205000-00009. PMID 11979093
- BACKGROUNDBhargava 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. doi: 10.1080/10428190310001625890. PMID 15291365
- BACKGROUNDBirkeland 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. doi: 10.1097/01.TP.0000085602.22498.CF. PMID 14508366
- RESULTRoswarski J, Roschewski M, Lucas A, Melani C, Pittaluga S, Jaffe ES, Steinberg SM, Waldmann TA, Wilson WH. Phase I dose escalation study of the anti-CD2 monoclonal antibody, siplizumab, with DA-EPOCH-R in aggressive peripheral T-cell lymphomas. Leuk Lymphoma. 2018 Jun;59(6):1466-1469. doi: 10.1080/10428194.2017.1387908. Epub 2017 Oct 16. No abstract available. PMID 29032710