Aplastic Anemia Clinical Trial
Official title:
A Randomized Trial of Immunosuppression in Aplastic Anemia Patients With Refractory Pancytopenia or Suboptimal Hematologic Response After h-ATG/CsA Treatment
Verified date | June 2021 |
Source | National Institutes of Health Clinical Center (CC) |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
Severe aplastic anemia, characterized by pancytopenia and a hypocellular bone marrow, is effectively treated by immunosuppressive therapy, usually a combination of antithymocyte globulin (ATG) and cyclosporine (CsA). Survival rates following this regimen are equivalent to those achieved with allogeneic stem cells transplantation. However, approximately 1/3 of patients will not show blood count improvement after ATG/CsA. General experience and small pilot studies have suggested that such patients may benefit from further immunosuppression. Furthermore, analysis of our own clinical data suggest that patients with poor blood count responses to a single course of ATG, even when transfusion-independence is achieved, have a markedly worse prognosis than patients with robust hematologic improvement. The management of such cases is uncertain. This study will enroll patients who are either refractory to h-ATG (continued severe pancytopenia) or who have only modest improvement in blood counts (weak hematologic responders) to receive a further immunosuppressive therapy, delivered either as rabbit ATG (Thymoglobulin, r-ATG) or a humanized monoclonal antibody to T-cells, alemtuzumab (Campath-1H ). Primary endpoint will be response rate at 3 months defined as no longer meeting criteria for severe aplastic anemia. Relapse, robustness of hematopoietic recovery at 3 months, survival and clonal evolution to paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia and acute leukemia will be the secondary endpoints.
Status | Completed |
Enrollment | 54 |
Est. completion date | February 5, 2016 |
Est. primary completion date | December 29, 2010 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 2 Years and older |
Eligibility | - INCLUSION CRITERIA: Severe aplastic anemia confirmed at NIH by: Bone marrow cellularity less than 30% (excluding lymphocytes) At least two of the following: Absolute neutrophil count less than 500/microL; Platelet count less than 20,000/ microL; Reticulocyte count less than 60,000/ microL. Severe aplastic anemia refractory to prior course(s) of h-ATG/CsA defined after 3 months from treatment with less or equal to 4 years from receiving h-ATG. OR Suboptimal response to initial immunosuppression with h-ATG/CsA as defined by platelet and reticulocyte count less than 50,000 /microL at 3 months. Age greater than or equal to 2 years of age EXCLUSION CRITERIA: Diagnosis of Fanconi anemia. Evidence of a clonal disorder on cytogenetics. Patients with super severe neutropenia (ANC less than 200/microL) will not be excluded initially if results of cytogenetics are not available or pending. If evidence of a clonal disorder is later identified, the subject will go off study. Prior treatment courses with rabbit ATG or high dose cyclophosphamide (200 mg/kg or equivalent). Infection not adequately responding to appropriate therapy. Underlying immunodeficiency state including seropositivity for HIV. Failure to discontinue the herbal supplements Echinacea purpurea or Usnea barbata (Old Man's Beard) within two weeks of enrollment. Previous hypersensitivity to Campath-1H or its components. 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. Potential subjects with cancer who are on active chemotherapeutic treatment or who take drugs with hematological effects will not be eligible. Serum creatinine greater than 2.5 mg/dL. Current pregnancy or lactation or unwillingness to take contraceptives. Inability to understand the investigational nature of the study or give informed consent. |
Country | Name | City | State |
---|---|---|---|
United States | National Institutes of Health Clinical Center, 9000 Rockville Pike | Bethesda | Maryland |
Lead Sponsor | Collaborator |
---|---|
National Heart, Lung, and Blood Institute (NHLBI) |
United States,
Mathé G, Amiel JL, Schwarzenberg L, Choay J, Trolard P, Schneider M, Hayat M, Schlumberger JR, Jasmin C. Bone marrow graft in man after conditioning by antilymphocytic serum. Br Med J. 1970 Apr 18;2(5702):131-6. — View Citation
Stein RS, Means RT Jr, Krantz SB, Flexner JM, Greer JP. Treatment of aplastic anemia with an investigational antilymphocyte serum prepared in rabbits. Am J Med Sci. 1994 Dec;308(6):338-43. — View Citation
Young NS, Maciejewski J. The pathophysiology of acquired aplastic anemia. N Engl J Med. 1997 May 8;336(19):1365-72. Review. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Participants no Longer Meeting Criteria for Severe Aplastic Anemia. | Number of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment at 6 months | 6 months | |
Secondary | Number of Participants With Robust Hematologic Recovery With Reticulocyte or Platelet Count | Number of participants with robust hematologic recovery with reticulocyte or platelet count = 50,000/uL | 6 months | |
Secondary | Percentage of Cumulative Incidence of Relapse in Participants | Percentage of cumulative incidence of relapse of disease in participants | 3 year | |
Secondary | Percentage of Cumulative Incidence of Clonal Evolution in Participants | Percent of cumulative incidence of clonal evolution in participants to either paroxysmal nocturnal hemoglobinuria (PNH), myelodysplasia or acute leukemia. | 3 years | |
Secondary | Percentage of Participants no Longer Meeting Criteria for Severe Aplastic Anemia. | Percentage of participants no longer meeting the criteria for severe aplastic anemia as measured by response to treatment | 3 months and 6 months |
Status | Clinical Trial | Phase | |
---|---|---|---|
Active, not recruiting |
NCT03025698 -
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
|
Phase 2 | |
Completed |
NCT00987480 -
Hematopoietic Stem Cell Transplantation for the Treatment of Patients With Fanconi Anemia Lacking a Genotypically Identical Donor, Using a Chemotherapy Only Cytoreduction With Busulfan, Cyclophosphamide and Fludarabine
|
Phase 2 | |
Completed |
NCT00767650 -
Neuropsychological Effects of Immunosuppressive Treatment in Subjects With Aplastic Anemia
|
N/A | |
Not yet recruiting |
NCT02833493 -
Study of MRI Monitoring in Patients With Aplastic Anemia and Low or Int-1 Risk of MDS Complicated With Iron Overload
|
N/A | |
Completed |
NCT02833805 -
NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia
|
Phase 2 | |
Recruiting |
NCT02028416 -
Comparison of Two Different Doses of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia
|
N/A | |
Completed |
NCT00004474 -
Phase III Randomized Study of Cyclophosphamide With or Without Antithymocyte Globulin Before Bone Marrow Transplantation in Patients With Aplastic Anemia
|
Phase 3 | |
Recruiting |
NCT05031897 -
Reduced-Intensity Conditioning for the Prevention of Treatment-Related Mortality in Patients Who Undergo a Hematopoietic Stem Cell Transplant
|
Phase 2 | |
Completed |
NCT04439006 -
Ibrutinib for the Treatment of COVID-19 in Patients Requiring Hospitalization
|
Phase 1 | |
Not yet recruiting |
NCT05996393 -
CsA+ATG+AVA vs. CsA+AVA for the Treatment of Newly-diagnosed SAA in the Elderly
|
Phase 4 | |
Completed |
NCT02462252 -
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
|
Phase 2 | |
Completed |
NCT01272817 -
Nonmyeloablative Allogeneic Transplant
|
N/A | |
Completed |
NCT00513175 -
Non-Myeloablative Allogeneic Stem Cell Transplantation With Matched Unrelated Donors for Treatment of Hematologic Malignancies, Renal Cell Carcinoma, and Aplastic Anemia
|
N/A | |
Completed |
NCT00001398 -
Stem Cell Factor Medication for Aplastic Anemia
|
Phase 1 | |
Recruiting |
NCT01861093 -
Safety Study of Cord Blood Units for Stem Cell Transplants
|
Phase 2 | |
Not yet recruiting |
NCT05018936 -
Efficacy and Safety of Hetrombopag in Non-severe Aplastic Anemia
|
Phase 2/Phase 3 | |
Recruiting |
NCT02007811 -
Open-label Clinical Trial to Investigate the Safety and Tolerability of Allogeneic B-cell Concentrates for Immune Reconstitution After Allogeneic Stem Cell Transplantation Measured as Response to a Antedated Single Vaccination
|
Phase 1/Phase 2 | |
Recruiting |
NCT01758042 -
Bone Marrow and Kidney Transplant for Patients With Chronic Kidney Disease and Blood Disorders
|
N/A | |
Terminated |
NCT01500161 -
Pooled Unrelated Donor Umbilical Cord Blood Transplant For Hematologic Malignancy Needing Allogeneic Stem Cell Transplant Without Related HLA-Match
|
Phase 2 | |
Recruiting |
NCT00881933 -
Study of Fludarabine + Cyclophosphamide + TBI Conditioning Regimen for Double Units Cord Blood Transplantation(CBT)in Severe Aplastic Anemia(SAA)
|
Phase 1/Phase 2 |