Extended Dosing With Eltrombopag for Severe Aplastic Anemia

Related Clinical Trial
Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia Long Term Follow-up Observational Study After Clinical Trials of AMG531 (Romiplostim) in Patients With Untreated Aplastic Anemia Efficacy and Safety of Lower-dose Decitabine in Refractory Aplastic Anemia Quantitative MRI of Bone Marrow Fat Fraction in Patients With Trepanobiopsy Avatrombopag Usage in NSAA Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization Retrospective Study of Patients With Severe Aplastic Anemia Who Relapsed After Immunosuppressive Therapy Retrospective Study of Patients With Severe Aplastic Anemia Who Developed High Risk Clonal Evolution With Chromosome 7Abnormalities After Immunosuppressive Therapy REGN7257 in Adult Patients With Severe Aplastic Anemia That Is Refractory to or Relapsed on Immunosuppressive Therapy Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs) Investigation of the Cylex® ImmuKnow® Assay Cytokine-Treated Veto Cells in Treating Patients With Hematologic Malignancies Following Stem Cell Transplant Umbilical Cord Blood Transplantation From Unrelated Donors Patient-Driven Transfusion Thresholds in Hematological Disorders: A Pilot Study Unrelated Umbilical Cord Blood (UBC)Transplantation New York Blood Center National Cord Blood Program Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match Bone Marrow Transplantation of Patients in Remission Using Partially Matched Relative Donor Nonmyeloablative Allo SCT for the Treatment of Hematologic Disorders Nonmyeloablative Allogeneic Stem Cell Transplantation From HLA-Matched Unrelated Donor for the Treatment of Hematologic Disorders Post Transplant Cyclophosphamide (Cytoxan) for GvHD Prophylaxis Effects of Aerobic Training and Inspiratory Muscle Training in Patients During Hematopoietic Stem Cell Transplantation A Phase II Study of Umbilical Cord Blood Transplantation Transplants With Unlicensed Preserved Cord Blood Safety Study of Cord Blood Units for Stem Cell Transplants Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation Screening Gene Mutations in Myeloid Cancers by Next Generation Sequencing to Improve Treatment Results Safety Study of CD3/CD19 Depleted Haploidentical Stem Cells Trial of Two Central Venous Catheter (CVC) Flushing Schemes in Pediatric Hematology and Oncology Patients Blood Transplantation for Patients With Hematologic Malignancies or Bone Marrow Failure States Unrelated Cord Blood Transplant Plus a Haplo-Identical (Half-Matched), T-Cell Depleted Stem Transplant From a Related Donor for Subjects With High Risk Malignancies Extended Platelet Parameters as a Means to Differentiate Immune Thrombocytopenia From Hypo-proliferative Thrombocytopenias. Protection Against Benzene Toxicity Treatment of Menorrhagia in Women With Thrombocytopenia Using Platelets or Platelets and Hormones Risk Stratification Directed Conditioning Regimen for Haploidentical HSCT in SAA Etiology of Blood Dyscrasias: Analysis of the International Agranulocytosis and Aplastic Anemia Study Data Multi-Center Trial of Anti-Thymocyte Globulin in Treatment of Aplastic Anemia and Other Hematologic Disorders King’s Invasive Aspergillosis Study II Identification of Mechanism in the Erythroid Response in Patients With Myelodysplasia Undergoing Chelation Therapy Aplastic Anemia Epidemiology: Incidence and Case-control Drug Etiology of Aplastic Anemia and Related Dyscrasias hATG+CsA vs hATG+CsA+Eltrombopag for SAA Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia Conditioning Regimens for Patients With Severe Aplastic Anemia Transplanted With Marrow From an Unrelated Donor Study of Allogeneic Bone Marrow and T-Cell Depleted, CD34+ Peripheral Blood Stem Cell Transplantation in Patients With Aplastic Anemia Posaconazole Prophylaxis During ATG Treatment for hMDS/AA Patients Efficacy and Safety of Thrombopoietin In Patients With Severe and Very Severe Aplastic Anemia Study of MRI Monitoring in Patients With Aplastic Anemia and Low or Int-1 Risk of MDS Complicated With Iron Overload A Pilot Study of the Thrombopoietin-Receptor Agonist Eltrombopag in Refractory Aplastic Anemia Patients Phase IIA Open Label Study to Evaluate Efficacy and Safety of BL-8040 Followed by (hATG), Cyclosporine and Methyprednisolone in Adult Subjects With Aplastic Anemia or Hypoplastic Myelodysplastic Syndrome Sirolimus and Cyclosporine for Treatment-Resistant Aplastic Anemia Flu+CPM+rATG Conditioning Regimes for Unrelated Bone Marrow Transplantation (UBMT)(or Mobilized Peripheral Blood)in Severe Aplastic Anemia (SAA) Unrelated Umbilical Cord Blood Transplantation for Severe Aplastic Anemia and Hypo-plastic MDS Using CordIn(TM), Umbilical Cord Blood-Derived Ex Vivo Expanded Stem and Progenitor Cells to Expedite Engraftment and Improve Transplant Outcome Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia Safety and Efficacy Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat Severe Aplastic Anemia Eltrombopag in Combination With Rabbit Anti-thymocyte Globulin/Cyclosporine A in Naive Aplastic Anemia (AA) Subjects Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia Methylprednisolone, Horse Anti-Thymocyte Globulin, Cyclosporine, Filgrastim, and/or Pegfilgrastim or Pegfilgrastim Biosimilar in Treating Patients With Aplastic Anemia or Low or Intermediate-Risk Myelodysplastic Syndrome Efficacy and Safety of Eltrombopag + CSA in Patients With Moderate Aplastic Anemia (EMAA) Allogeneic Stem Cell Transplantation for Patients With Severe Aplastic Anemia Multi Center Case Control Study on Multiple Risk Factors of Aplastic Anemia NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia Horse ATG/CsA in Aplastic Anemia Patients Unresponsive to or With a Suboptimal Response to Rabbit ATG/CsA Treatment Safety and Efficacy Study of Ex Vivo Immunotherapy for Treatment of Aplastic Anemia Phase II Study of Bone Marrow Transplantation Using Related Donors in Patients With Aplastic Anemia Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA) Haploidentical Transplantation in Severe Aplastic Anemia A Description of Bacteria in the Mouths of Patients With Severe Aplastic Anemia Efficacy and Safety of Eltrombopag + Tacrolimus in Chinese Refractory or Relapsed Aplastic Anemia Patients A Study to Evaluate the Safety and Efficacy of Hetrombopag Olamine in Severe Aplastic Anemia (SAA) Patient Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Cyclophosphamide and Anti-thymocyte Globulin Followed By Methotrexate and Cyclosporine in Preventing Chronic Graft-Versus-Host Disease in Patients With Severe Aplastic Anemia Undergoing Donor Bone Marrow Transplant Peripheral Blood Allogenic Stem Cell Transplantation Using Non-anti Thymocyte Globulin Regimens in Severe Aplastic Anemia Patients A Phase 2 Study to Evaluate the Efficacy and Safety of AMG531 in Aplastic Anemia Sirolimus (Rapamune ) for Relapse Prevention in People With Severe Aplastic Anemia Responsive to Immunosuppressive Therapy Phase III Randomized Study of Cyclophosphamide With or Without Antithymocyte Globulin Before Bone Marrow Transplantation in Patients With Aplastic Anemia Anti-thymocyte Globulin and Cyclosporine as First-Line Therapy in Treating Patients With Severe Aplastic Anemia Cyclophosphamide, Antithymocyte Globulin, and Total-Body Irradiation in Treating Patients With Severe Aplastic Anemia Undergoing Umbilical Cord Blood Transplant Purified CD34+ Hematopoietic Stem Cell Transplantation From Alternate Donors for Patients With Severe Aplastic Anemia Stem Cell Factor Medication for Aplastic Anemia Thymoglobulin and Cyclosporine in Patients With Aplastic Anemia or Myelodysplastic Syndrome Extended Dosing With Eltrombopag for Severe Aplastic Anemia Randomized Study In Severe Aplastic Anemia Patients Receiving Atg, Cyclosporin A, With Or Without G-CSF (SAA-G-CSF) Umbilical Cord Derived Mesenchymal Stem Cells Therapy in Aplastic Anemia Stem Cell Mobilization Potential in Patients With Aplastic Anemia in Remission A Phase II Dose-escalation Study Characterizing the PK of Eltrombopag in Pediatric Patients With Previously Untreated or Relapsed Severe Aplastic Anemia or Recurrent Aplastic Anemia Eltrombopag With Standard Immunosuppression for Severe Aplastic Anemia Mycophenolate Mofetil and Cyclosporine to Treat Relapsing Aplastic Anemia Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia Collection of Blood and Bone Marrow From Patients With Aplastic Anemia for Analysis of Adhesion Molecules, Chemokines and Their Receptors Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia Alefacept in Patients With Relapsed/Refractory Aplastic Anemia Oral Manifestations of Aplastic Anemia The Efficacy of Immunosuppressive Therapy Combined With Cord Blood Transfusion in Treatment of Severe Aplastic Anemia Clinical Study of Non Severe Aplastic Anemia Treated With Cyclosporine, Androgen and Levamisole Mesenchymal Stem Cells Transplantation to Patients With Relapsed/Refractory Aplastic Anemia. Safety and Efficacy of Exjade in the Treatment of Transfusion-dependent Iron Overload in Aplastic Anemia Patients Cyclophosphamide Plus Cyclosporine in Treatment-Naive Severe Aplastic Anemia Neuropsychological Effects of Immunosuppressive Treatment in Subjects With Aplastic Anemia Unrelated Donor Transplant Versus Immune Therapy in Pediatric Severe Aplastic Anemia Reduced Toxicity Fludarabine (Flu) + Cyclophosphamide (CPM) + Rabbit Antithymocyte Globulin (rATG) Conditioning Regimen for Unrelated Donor Transplantation in Severe Aplastic Anemia (SAA) ATG Combined With Cyclophosphamide And Cord Blood Transfusion in Treating Patients With Severe Aplastic Anemia A Novel TBI Free Conditioning Protocol for Haploidentical Transplant in Acquired Aplastic Anemia: Combination Therapy of Severe Aplastic Anemia Comparing Therapies for the Treatment of Severe Aplastic Anemia Mesenchymal Stem Cells Co-transplantation in Alternative Donor Transplantation of Severe Aplastic Anemia. Study of AMG531(Romiplostim) in Patients With Aplastic Anemia Bone Marrow Transplant Trial for Patients With Refractory Severe Aplastic Anemia Study of AMG531 (Romiplostim) in Patients With Aplastic Anemia Improving Immunosuppressive Treatment for Patients With Severe Aplastic Anemia Study of Romiplostim(AMG531) in Subjects With Aplastic Anemia A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia Rabbit Antithymocyte Globulin (Thymoglobuline) With Ciclosporin for Patients With Acquired Aplastic Anaemia Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia A Study to Assess Efficacy and Safety of PF-06462700 in Japanese Participants With Aplastic Anemia Alemtuzumab and Rituximab in Aplastic Anemia Allogeneic Stem Cell Transplant for Patients With Severe Aplastic Anemia Comparison of Two Different Doses of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia Mesenchymal Stem Cells in the Treatment of Relapsed/Refractory Severe Acquired Aplastic Anemia Study of Fludarabine + Cyclophosphamide + TBI Conditioning Regimen for Double Units Cord Blood Transplantation(CBT)in Severe Aplastic Anemia(SAA) Safety and Efficacy of Patient’s Own AD-MSC and AD-HSC Transplantation in Patients With Severe Aplastic Anemia Ambispective Observational Study to Evaluate the Incidence and Management of Aplastic Anemia in Spain Moderate-dose Cyclophosphamide for Childhood Acquired Aplastic Anemia

Brief Title

Extended Dosing With Eltrombopag for Severe Aplastic Anemia

Official Title

Extended Dosing With Eltrombopag in Refractory Severe Aplastic Anemia

Brief Summary

      Background:

      - Eltrombopag is a drug being tested for treating severe aplastic anemia. It can help improve
      blood counts in these patients. However, researchers do not know how long the drug can and
      should be taken for this type of anemia.

      Objectives:

      - To look at whether 6 months of treatment with eltrombopag can improve patient s blood
      counts.

      Eligibility:

      - Individuals at least 2 years of age who are taking eltrombopag for severe aplastic anemia.

      Design:

        -  Participants will take eltrombopag by mouth once a day for 6 months.

        -  Blood samples will be collected every 2 weeks for the first 6 months. Bone marrow
           samples will be collected at 3 and 6 months. These samples will look at the effects of
           the study drug on the marrow.

        -  Participants will continue to take the study drug for as long as it is effective and if
           the side effects are not severe.
    

Detailed Description

      Severe aplastic anemia (SAA) is a life-threatening blood disease that can be successfully
      treated with immunosuppressive drug regimens or allogeneic stem cell transplantation.
      However, 20-40% of patients are ineligible for transplant due to lack of an appropriate
      donor, age, or comorbidities. Immunosuppression can be more broadly utilized, but about 1/3
      of patients do not respond to a single course of horse ATG and cyclosporine and have
      persistent severe cytopenias. Among patients who do respond to immunosuppression, responses
      may be partial, with persistent thrombocytopenia, neutropenia, and/or anemia. About 30% of
      responding patients either relapse or are dependent on continued cyclosporine administration.
      Patients with refractory severe cytopenias are at risk of dying from infection or bleeding,
      and they require regular platelet and/or red blood cell transfusions, which are expensive and
      inconvenient, Patients with refractory SAA are also at risk for progression to other
      hematologic disorders, including myelodysplasia and leukemia.

      Thrombopoietin (TPO) was first identified as the principal protein regulating platelet
      production, and it stimulates the proliferation of megakaryocytes and release of platelets.
      TPO was later shown to stimulate proliferation of more primitive bone marrow stem and
      progenitor cells in vitro and in animal models, suggesting it could have an impact of
      production of red and white blood cells as well as platelets.

      The 2nd generation oral small molecule TPO-agonist eltrombopag (Promacta ) has been shown to
      increase platelets in healthy subjects and in thrombocytopenic patients with chronic immune
      thrombocytopenic purpura (ITP) and hepatitis C virus (HCV)-infection. Eltrombopag has been
      well-tolerated in clinical trials, and unlike recombinant TPO, it does not induce
      autoantibodies. Eltrombopag received FDA accelerated approval on November 20, 2008 for the
      treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenic
      purpura who have had an insufficient response to corticosteroids, immunoglobulins, or
      splenectomy. In November 2012, FDA approval was received for hepatitis C associated
      thrombocytopenia.

      We conducted a pilot dose finding study in patients with severe aplastic anemia who had
      refractory thrombocytopenia following standard immunosuppressive therapy. Patients began at a
      dose of 50 mg/day and escalated every two weeks to a maximum dose of 150 mg/day. We reported
      that 11 of 25 patients (44%) achieved hematological response in at least one lineage
      following 12 weeks of dose-escalating eltrombopag therapy, with minimal toxicity. Responding
      patients as assessed at 12 weeks were invited to continue on drug in an extension phase. With
      a median follow-up of 27 months on drug, 7 eventually became tri-lineage responders. Nine
      became transfusion-independent for platelets (median increase in platelet count 34,000/micro
      l), six had improved hemoglobin levels (median increase of 3.8g/dL), including three
      previously dependent on red cell transfusions achieving transfusion-independence, and eight
      exhibiting increased neutrophil counts (median increase 590 cells/mico L). Serial bone marrow
      biopsies demonstrated normalization of tri-lineage hematopoiesis in responders, without
      increased fibrosis.

      In the previous study, response assessment occurred at 12 weeks, and patients not fulfilling
      response criteria at that time had the drug discontinued. Several patients began to have
      detectable changes in transfusion requirements or blood counts by 12 weeks, but did not
      fulfill response criteria by that time point and therefore had to discontinue eltrombopag.
      Other patients who barely met response criteria at 12 weeks showed very marked further
      improvements in blood counts in all lineages during the extension phase, in some cases not
      reaching maximal responses until one year after initiating eltrombopag. We hypothesize that a
      larger fraction of patients may respond if eltrombopag is continued for longer than 12 weeks.

      We, therefore propose a follow-up Phase 2 study giving eltrombopag treatment for 24 weeks
      prior to definitive response assessment, and initiating study medication at a fixed dose of
      150 mg/day (75 mg /day for individuals of East Asian ethnicity), given lack of toxicity at
      that dose in the prior study, and no evidence for response in any patient during dose
      escalation prior to reaching this dose. Responses will be assessed in all three lineages.
      Subjects with platelet, red cell, and/or neutrophil responses at 24 weeks may continue study
      medication (extended access) until they meet off study criteria.

      The primary objective is to assess the efficacy of 6 months of eltrombopag administration in
      improving bone marrow function in SAA patients with persistent severe cytopenias refractory
      to treatment with immunosuppressive treatment.

      Secondary objectives include assessment of relapse or clonal evolution, pre-treatment
      characteristics predicting response, and the impact of treatment and treatment response on
      quality of life.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Number of Participants With Drug Response as Defined by Clinically-signficant Hematologic Improvements


Condition

Severe Aplastic Anemia (SAA)

Intervention

Eltrombopag

Study Arms / Comparison Groups

 Eltrombopag
Description:  Administration of eltrombopag at a dose of 150mg/day for 6 months

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

Drug

Estimated Enrollment

40

Start Date

June 28, 2013

Completion Date

December 31, 2021

Primary Completion Date

October 16, 2017

Eligibility Criteria

        -  INCLUSION CRITERIA:

          -  Previous diagnosis of refractory severe aplastic anemia and following at least one
             treatment course of immunosuppression with a regimen containing antithymocyte
             globulin, alemtuzumab or cyclophosphamide.

          -  One or more of the following three clinically-significant cytopenias: platelet count
             less than or equal to 30,000/micro L or platelet-transfusion-dependence (requiring at
             least 4 platelet transfusions in the 8 weeks prior to study entry); neutrophil count
             less than 500/micro L; hemoglobin less than 9.0 g/dL or red cell
             transfusion-dependence (requiring at least 4 units of PRBCs in the eight weeks prior
             to study entry)

          -  Age greater than or equal to 2 years old

          -  Weight > 12 kg

        EXCLUSION CRITERIA:

          -  Infection not adequately responding to appropriate therapy

          -  Evidence of a clonal disorder on cytogenetics performed within 12 weeks of study
             entry.

          -  Creatinine > 2.5 mg/dL

          -  Direct Bilirubin > 2.0 mg/dL

          -  SGOT or SGPT >5 times the upper limit of normal

          -  Hypersensitivity to eltrombopag or its components

          -  Female subjects who are nursing or pregnant or are unwilling to take oral
             contraceptives or refrain from pregnancy if of childbearing potential

          -  Unable to understand the investigational nature of the study or give informed consent

          -  Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary,
             infectious, or metabolic disease of such severity that it would preclude the patient s
             ability to tolerate protocol therapy, or that death within 7-10 days is likely

          -  Treatment with ATG, cyclophophamide or alemtuzamab within 6 months of study entry.
      

Gender

All

Ages

2 Years - 100 Years

Accepts Healthy Volunteers

No

Contacts

Cynthia E Dunbar, M.D., , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT01891994

Organization ID

130133

Secondary IDs

13-H-0133

Responsible Party

Sponsor

Study Sponsor

National Heart, Lung, and Blood Institute (NHLBI)


Study Sponsor

Cynthia E Dunbar, M.D., Principal Investigator, National Heart, Lung, and Blood Institute (NHLBI)


Verification Date

March 2021