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

Learn more about:
Related Clinical Trial
A Phase 1, Study of CD4-Targeted Chimeric Antigen Receptor T-Cells (CD4- CAR-T) in Subjects With Relapsed or Refractory T-Cell Lymphoma CAR T-cells Against CD30 (HSP-CAR30) for Relapsed/ Refractory Hodgkin and T-cell Lymphoma. A Safety and Efficacy Study Evaluating CTX130 in Subjects With Relapsed or Refractory T or B Cell Malignancies A Clinical Trial of Chidamide Combined With Etoposide in Relapsed or Refractory NK/T-cell Lymphoma A Study of Evaluating the Safety and Efficacy of ATG-010 Combined With Chemotherapy Sequential With ATG-010 Monotherapy Maintenance in Peripheral T- and NK/T-cell Lymphoma Duvelisib Maintenance After Autologous Stem Cell Transplant in T-Cell and Indolent B-Cell Lymphomas Study of Brentuximab Vedotin as Therapy After Autologous Stem Cell Transplant in Cluster of Differentiation Antigen 30 (CD30) Positive Peripheral TCell Lymphomas AMG 319 Lymphoid Malignancy FIH Total Body Irradiation +/- Total Lymphoid Irradiation & Anti-Thymocyte Globulin in Non-myeloablative Hematopoietic Cell Transplantation Palbociclib in Combination With Chemotherapy in Treating Children With Relapsed Acute Lymphoblastic Leukemia (ALL) or Lymphoblastic Lymphoma (LL) PD-1 Knockout EBV-CTLs for Advanced Stage Epstein-Barr Virus (EBV) Associated Malignancies Tandem Auto-Allo Transplant for Lymphoma Anti-CD30 CAR-T Therapy in Patients With Refractory/Relapsed Lymphocyte Malignancies Study of Infusion of Blood Cells (Lymphocytes) to Stimulate the Immune System to Fight Leukemia/Lymphoma Long-term Follow-up of Patients Treated With Autologous T Cells Genetically Modified Subcutaneous Recombinant Human IL-15 (s.c. rhIL-15) and Alemtuzumab for People With Refractory or Relapsed Chronic and Acute Adult T-cell Leukemia (ATL) Study of AZD5991 in Relapsed or Refractory Haematologic Malignancies. p53/p16-Independent Epigenetic Therapy With Oral Decitabine/Tetrahydrouridine for Refractory/Relapsed Lymphoid Malignancies Investigation of the Human Immune Response in Normal Subjects and Patients With Disorders of the Immune System and Cancer Study of IPI-145 in Combination With Rituximab or Bendamustine/Rituximab in Hematologic Malignancies A Phase II Study Of Imtox-25 In Adults With Refractory/Relapsed Cd25 Positive Adult T Cell Leukemia/Lymphoma Phase 1 Trial of Siplizumab and Dose-Adjusted EPOCH-Rituximab in T- and NK-Cell Lymphomas CD4CAR for CD4+ Leukemia and Lymphoma Pembrolizumab for T/NK-cell lymphomasNK-cell Lymphomas Study of CHOP + Campath for T-Cell, Null Cell, or Natural Killer (NK)-Cell Lymphoma Anti-CD7 U-CAR-T Cell Therapy for T/NK Cell Hematologic Malignancies Safety and Efficacy Study of a Dual PI3K Delta/Gamma Inhibitor in Hematological Malignancies Dose Escalation Study of Clofarabine in Patients With Relapsed or Refractory Low Grade or Intermediate-Grade B-Cell Lymphoma Chemoimmunotherapy and Allogeneic Stem Cell Transplant for NK T-cell Leukemia/Lymphoma A Study for Patients With Non-Hodgkin’s Lymphomas High Risk Adult T-cell Leukemia/Lymphoma (ATLL-HR) and Allogeneic Transplant Phase 1 Trial of ST-001 nanoFenretinide in Relapsed/Refractory T-cell Non-Hodgkin Lymphoma CPI-613 in Combination With Bendamustine in Patients With Relapsed/Refractory T-Cell Non-Hodgkin Lymphoma Allo-HSCT as First-line Consolidation in High-risk PTCL A Single Arm Study Evaluating the Efficacy and Safety of Pralatrexate in Subjects With Relapsed or Refractory PTCL PD1 Combined With Apatinib in Patients With Relapsed or Refractory NK/T Cell Lymphoma Lenalidomide Therapy for Patients With Relapsed and/or Refractory, Peripheral T-Cell Lymphomas An Open Label, International, Multi-centre, Phase I/IIa Study of Lenalidomide (Revlimid) and Romidepsin (Istodax) for Relapsed /Refractory Hodgkin Lymphoma, Mature T-cell Lymphoma and Multiple Myeloma. (RId Study) A Phase II Study of Single Agent Brentuximab Vedotin in Relapsed/Refractory CD30 Low ( T-cell Brazil: Prospective Collection of Data in T-cell Lymphomas Patients A-dmDT390-bisFv(UCHT1) Immunotoxin Therapy for Patients With Cutaneous T-Cell Lymphoma (CTCL) Efficacy and Safety of Oral HBI-8000 in Patients With Relapsed or Refractory Adult T Cell Lymphoma (ATL) Orally Fludarabine, Adriamycin and Dexamethasone (FAD) in Newly Diagnosed Peripheral T-cell Lymphomas (PTCL) ECHELON-2: A Comparison of Brentuximab Vedotin and CHP With Standard-of-care CHOP in the Treatment of Patients With CD30-positive Mature T-cell Lymphomas Phase I Dose-finding and Preliminary Efficacy Study of the Istodax® in Combination With Doxil® for the Treatment of Adults With Relapsed or Refractory Cutaneous T-cell Lymphoma Nivolumab in Combination With GDP/ L-asparaginase in NK/ T-cell Lymphoma Bendamustine, Carboplatin and Dexamethasone (BCD) for Refractory or Relapsed Peripheral T-cell Lymphoma Combination Therapy With Carfilzomib, Romidepsin, Lenalidomide in Patients With Relapsed or Refractory B- and T-cell Lymphomas Helical Irradiation of Total Skin (HITS) for T Cell Lymphoma Efficacy of a Treatment With CHOP and Lenalidomide in First Line in Angioimmunoblastic T-cell Lymphoma (AITL) CD7 CAR-T Cells for Patients With R/R CD7+ NK/T Cell Lymphoma,T-lymphoblastic Lymphoma and Acute Lymphocytic Leukemia A Multicenter Clinical Trial of Daratumumab in Combination With Gemcitabine, Dexamethasone and Cisplatin in Patients With Relapsed/Refractory CD38 Positive PTCL-NOS, Angioimmunoblastic T-cell Lymphoma AITL and Other Nodal Lymphomas of T Follicular Helper Cells Origin Avelumab in Relapsed and Refractory Peripheral T-cell Lymphoma Use of Venetoclax as Single Agent in Patients With Relapsed/Refractory BCL-2 Positive Peripheral T Cell Lymphoma Efficacy and Safety Study of Fostamatinib Disodium Tablets to Treat T-Cell Lymphoma A Study of Improving the Efficacy of Treatment in High Risk T Cell Lymphoma Patients A Phase II Clinical Trial of Lenalidomide for T-cell Non-Hodgkin’s Lymphoma HuMax-CD4 in Non-Cutaneous T-Cell Lymphoma Gemcitabine in NK/T Cell Lymphoma A Pilot Study of Oncaspar® + Dexamethasone in Patients With Relapsed or Refractory T-Cell Lymphoma PD-1 Antibody, Chidamide, Lenalidomide and Etoposide for Relapsed or Refractory NK/T Cell Lymphoma Trial of Endostar Combined With CHOPT for T Cell Lymphoma Intratumoral Poly-ICLC Plus Low Dose Local Radiation in Low Grade Recurrent B and T Cell Lymphoma Study of Ibrutinib in Relapsed and Refractory T-cell Lymphoma A Dose Escalation Study Evaluating CPI-818 in Relapsed/Refractory T-Cell Lymphoma Endostar Combined With CHOP Regimen as First Line Chemotherapy for Peripheral T Cell Lymphoma LAMPP Trial for Peripheral and Cutaneous T-Cell Lymphoma LCAR-T2C CAR-T Cells in Relapsed or Refractory CD4+ T-cell Lymphoma CD4 in Combination With CHOP in Treating Non-cutaneous Peripheral TCell Lymphoma Bendamustine in Patients With Refractory or Relapsed T-cell Lymphoma A Pilot Study of Sorafenib Examining Biomarkers in Refractory or Relapsed T-Cell Lymphoma Patients Safety and Efficacy of Tenalisib (RP6530) in Combination With Romidepsin in Patients With Relapsed/Refractory T-cell Lymphoma

Brief Title

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

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 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.
    

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 Etoposide, Prednisone, Vincristine, Cyclophosphamide and
      Doxorubicin (EPOCH) chemotherapy was evaluated in patients with chemotherapy naive aggressive
      T and natural killer (NK) cell lymphoid malignancy. Dose-limiting bone marrow toxicity
      prevented escalation of the alemtuzumab dose.

      Siplizumab is a humanized monoclonal antibody directed at cluster of differentiation 2 (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 Epstein-Barr Virus (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 and maximum tolerated dose of siplizumab and dose-adjusted EPOCH
      rituximab chemotherapy in chemotherapy naïve CD2- expressing T and NK lymphoid malignancies.

      Eligibility:

      CD2-expressing lymphoid malignancy.

      Patients with chemotherapy naive aggressive T & NK lymphomas. Patients with alk-positive
      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 Phase

Phase 1

Study Type

Interventional


Primary Outcome

Number of Participants With Serious and Non-serious Adverse Events

Secondary Outcome

 Number of Participants With a Response to Therapy

Condition

T-Cell Peripheral Lymphoma

Intervention

Rituximab

Study Arms / Comparison Groups

 siplizumab + EPOCH (combo chemo) + rituximab
Description:  siplizumab will be given with EPOCH (combo chemo) and rituximab every 21 days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Biological

Estimated Enrollment

15

Start Date

January 13, 2009

Completion Date

October 1, 2021

Primary Completion Date

April 1, 2011

Eligibility Criteria

        -  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.
      

Gender

All

Ages

18 Years - 120 Years

Accepts Healthy Volunteers

No

Contacts

Wyndham H Wilson, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01445535

Organization ID

090065

Secondary IDs

09-C-0065

Responsible Party

Principal Investigator

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Wyndham H Wilson, M.D., Principal Investigator, National Cancer Institute (NCI)


Verification Date

October 2020