Purine Analog-Based Conditioning in Patients With 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

Purine Analog-Based Conditioning in Patients With Severe Aplastic Anemia

Official Title

Purine Analog-Based Conditioning for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia

Brief Summary

      Primary Objectives:

        1. To determine the feasibility and toxicity of employing purine-analog based conditioning
           for allogeneic donor stem cell transplantation in patients with severe aplastic anemia
           (AA).

        2. To determine the engraftment kinetics and degree of chimerism that can be achieved with
           this strategy.
    

Detailed Description

      Before treatment starts, patients will have their bone marrow checked and will have lung,
      heart, and kidney tests.

      Patients in this study will receive the drugs fludarabine, cyclophosphamide, and
      antithymocyte globulin by vein through a previously inserted plastic catheter that extends
      into the large chest vein. Fludarabine will be given daily for four days, cyclophosphamide
      will given daily for four days, and antithymocyte globulin will be given daily for four days
      (three days for related donor transplants).

      Two days after the last dose of cyclophosphamide, donor marrow or stem cells will be infused
      through a catheter (thin plastic tube). Drugs will be given to lower the chance of an
      allergic reaction to the stem cells. Patients will also get shots of filgrastim (a drug that
      helps white blood cell growth) and antibiotics by mouth. The blood cell counts will fall to
      low levels during the first 2 weeks when patients may need transfusions of red blood cells
      and platelets. The chemotherapy will be given in the hospital. After the infusion of stem
      cells, patients will be monitored in the hospital. They will later be closely followed as
      outpatients and will be required to remain in the Houston area for about three months after
      the transplant.

      Drugs (cyclosporine and methotrexate) to lower the chance of graft-versus-host disease will
      be given. Cyclosporine will be given as a continuous infusion starting 2 days before
      transplantation. Methotrexate will be given through the catheter on Days 1, 3, 6 and 11 after
      transplantation. Cyclosporine will be given as pills when the patient is able to swallow.
      Cyclosporine will be continued for no less than 6 months after transplantation after which it
      will be gradually stopped. The drug tacrolimus may be used instead of cyclosporine.

      Blood, urine, bone marrow, and x-ray exams will be done as needed to monitor the results of
      bone marrow transplantation. Patients may require blood and platelet transfusions. Blood
      tests will be done daily while hospitalized and several times a week until the blood counts
      recover. Bone marrow aspiration and biopsies will be performed before the transplant, when
      the donated cells show signs of engraftment, and at other times during the next 1 to 3 years.
      They will be done to evaluate the growth of the transplant marrow, possible recurrence of
      malignancy, and recovery of immunity. If this treatment proves unsuccessful in more than
      three of the first ten patients, the study will be stopped.

      This is an investigational study. The FDA has approved all of the drugs in this study for
      other indications. Up to 30 patients will be treated on this study. All will be enrolled at
      M.D. Anderson.
    


Study Type

Interventional


Primary Outcome

Number of Patients With Engraftment Response


Condition

Aplastic Anemia

Intervention

Fludarabine

Study Arms / Comparison Groups

 Fludarabine + Cyclophosphamide + ATG
Description:  Fludarabine 30 mg/m^2/day by vein (IV), Cyclophosphamide IV 300 mg/m^2/day, ATG (Antithymocyte Globulin) IV 3.75 mg/kg/day

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

9

Start Date

December 2000

Completion Date

August 2009

Primary Completion Date

August 2009

Eligibility Criteria

        Inclusion Criteria:

          -  Patients up to 70 years of age with a diagnosis of severe AA (Camitta et al., 1979)
             and a matched unrelated donor who are unresponsive to IS or who have relapsed after an
             initial response to IS. Patients with a diagnosis of SAA and an human leukocyte
             antigen (HLA) - compatible sibling donor are eligible only if they are 40 years of age
             or older (up to age 70) and regardless whether they have received IS or not. Patients
             with primary or secondary graft failure following autologous or allogeneic stem cell
             transplant are eligible.

          -  Patients must have a serum bilirubin of 2 mg/dl or less, serum creatinine < 2.0 mg/dl,
             no symptomatic cardiac or pulmonary disease and a PS of no more than 2. Life
             expectancy not severely limited by concomitant illness (> 12 weeks). Left ventricular
             ejection fraction > 40%, no uncontrolled arrhythmia or symptomatic cardiac disease.
             Forced Expiratory Volume in 1 Second (FEV1), Forced Vital Capacity (FVC) and Carbon
             Monoxide Diffusing Capacity (DLCO) > 40%. No symptomatic pulmonary disease. Negative
             pregnancy test.

          -  Patients must have an HLA-compatible related or unrelated donor willing to donate
             marrow or rhG-CSF-mobilized peripheral blood stem cells. In the event of transplants
             from matched unrelated donors, a high-resolution allele match for HLA-A, -B, -C, -DRB1
             and DQB1 ("10 of 10 match") is preferred. However, a one-antigen mismatch
             ("micromismatch") is also considered acceptable matching ("9 of 10 match").

          -  Patients must sign informed consent. In the event of a pediatric patient (i.e., a
             minor), consent will be provided by their guardian/parent.

          -  Lack of clonal cytogenetic abnormalities associated with acute myeloid leukemia (AML),
             myelodysplastic syndrome (MDS) or other hematologic malignancies.

        Exclusion Criteria:

          -  Life expectancy of less than 8 weeks. Inability to provide informed consent.
      

Gender

All

Ages

N/A - 70 Years

Accepts Healthy Volunteers

No

Contacts

Paolo Anderlini, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00427336

Organization ID

IDP00-266


Responsible Party

Sponsor

Study Sponsor

M.D. Anderson Cancer Center


Study Sponsor

Paolo Anderlini, MD, Principal Investigator, M.D. Anderson Cancer Center


Verification Date

September 2011