Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas
Overview[ - collapse ][ - ]
| Purpose | 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 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 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 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 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. ... |
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| Condition | T-Cell Peripheral Lymphoma Gamma Delta Hepatosplenic T-Cell Lymphoma Subcutaneous Panniculitis-Like T-Cell Lymphoma NK T-Cell Lymphoma |
| Intervention | Drug: Siplizumab (Medi-507) Drug: Etoposide Drug: Cyclophosphamide Drug: Doxorubicin Drug: Vincristine Drug: Prednisone Drug: Rituximab |
| Phase | Phase 1 |
| Sponsor | National Cancer Institute (NCI) |
| Responsible Party | National Institutes of Health Clinical Center (CC) |
| ClinicalTrials.gov Identifier | NCT01445535 |
| First Received | September 30, 2011 |
| Last Updated | March 14, 2014 |
| Last verified | June 2013 |
Tracking Information[ + expand ][ + ]
| First Received Date | September 30, 2011 |
|---|---|
| Last Updated Date | March 14, 2014 |
| Start Date | January 2009 |
| Estimated Primary Completion Date | Not Provided |
| Current Primary Outcome Measures | Determine the toxicity of siplizumab and DA-EPOCH-R in chemotherapy na(SqrRoot) ve CD2-expressing T and NK lymphoid malignancies.Determine the maximum tolerated dose of siplizumab administered in combination with DA-EPOCH-R. |
| Current Secondary Outcome Measures | Determine anti-tumor activity of siplizumab-EPOCH-R.Determine the time course of B, T, and NK dell depletion and recovery. |
Descriptive Information[ + expand ][ + ]
| Brief Title | Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas |
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| Official Title | Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab (DA-EPOCH-R) in T and NK-Cell Lymphomas |
| Brief Summary | 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 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 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 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 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. ... |
| Detailed Description | 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. |
| Study Type | Interventional |
| Study Phase | Phase 1 |
| Study Design | Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment |
| Condition |
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| Intervention | Drug: Siplizumab (Medi-507) N/A Drug: Etoposide N/A Drug: Cyclophosphamide N/A Drug: Doxorubicin N/A Drug: Vincristine N/A Drug: Prednisone N/A Drug: Rituximab N/A |
| Study Arm (s) | Not Provided |
Recruitment Information[ + expand ][ + ]
| Recruitment Status | Active, not recruiting |
|---|---|
| Estimated Enrollment | 15 |
| Estimated Completion Date | Not Provided |
| Estimated Primary Completion Date | Not Provided |
| 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 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. |
| Gender | Both |
| Ages | 18 Years |
| Accepts Healthy Volunteers | No |
| Contacts | Not Provided |
| Location Countries | United States |
Administrative Information[ + expand ][ + ]
| NCT Number | NCT01445535 |
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| Other Study ID Numbers | 090065 |
| Has Data Monitoring Committee | Not Provided |
| Information Provided By | National Institutes of Health Clinical Center (CC) |
| Study Sponsor | National Cancer Institute (NCI) |
| Collaborators | Not Provided |
| Investigators | Principal Investigator: Wyndham H Wilson, M.D. National Cancer Institute (NCI) |
| Verification Date | June 2013 |
Locations[ + expand ][ + ]
| National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda, Maryland, United States, 20892 |
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