Brief Title
A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia
Official Title
A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia
Brief Summary
Severe acquired aplastic anaemia (SAA) is a bone marrow failure disease characterized by pancytopenia and a hypocellular bone marrow. The corn pathophysiological mechanism is the destruction of hematopoietic stem/progenitor cells mediated by auto-reactive effector T cells. Immunosuppressive therapy with horse antithymocyte globulin (ATG) plus cyclosporine (CSA) is currently the standard of treatment in patients with aplastic anaemia who are not eligible for bone marrow transplantation and with response rates from 40% to 70%. Previous studies showed that horse ATG (hATG) is apparently more effective than rabbit ATG (rATG) as the latter has higher treatment related mortality (TRM). Unfortunately hATG is unavailable in China, so we conduct a optimized standard treatment (9 days protocol) of rATG plus CSA and Levamisole (LMS) Sequential maintaining (termed Optimized Standard Protocol, OSP) for severe aplastic anemia. This prospective study is designed to evaluate the efficacy and safety of Optimized Standard Protocol as first line therapy in newly diagnosed severe aplastic anemia patients.
Detailed Description
During the treatment period, rATG is administered at a dose of 1.97 mg/kg/day for 9 days by slow intravenous infusion. CSA is administered orally at a dose of 3 mg/kg qod, and Levamisole was administered orally at a dose of 2.5 mg/kg qod. The CSA and Levamisole (LMS) is designed to alternately every other day.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
the response and complete remission rate with Optimized Standard Protocol.
Secondary Outcome
Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.
Condition
Aplastic Anemia
Intervention
rabbit ATG, Cyclosporine, Levamisole
Study Arms / Comparison Groups
Severe Aplastic Anemia
Description: Drug: rabbit ATG, Cyclosporine, Levamisole
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
August 2014
Completion Date
September 2017
Primary Completion Date
September 2016
Eligibility Criteria
Inclusion Criteria: - Newly diagnosed SAA (according to the standard criteria) 1. Bone marrow cellularity less than 30% (excluding lymphocytes) 2. At least two of the following: Absolute neutrophil count less than 500/ uL; Platelet count less than 20,000/ uL; Absolute reticulocyte count less than 20,000/ uL. - Age greater than or equal to 6 years old Exclusion Criteria: - Serum creatinine greater than 2.5 mg/dL - Underlying carcinoma (except local cervical, basal cell, squamous cell) - Prior immunosuppressive therapy with ATG, antilymphocyte globulin (ALG), or high dose cyclophosphamide. - Current pregnancy or lactation or unwillingness to take oral contraceptives or use an effective method of birth control. - Diagnosis of Fanconi anemia or other congenital bone marrow failure syndromes - Evidence of a clonal disorder on cytogenetics. Patients with super severe neutropenia (ANC less than 200/uL) will not be excluded if results of cytogenetics are not available or pending. - Underlying immunodeficiency state including seropositivity for HIV - Inability 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.
Gender
All
Ages
6 Years - 70 Years
Accepts Healthy Volunteers
No
Contacts
Zheng Yizhou, M.D., Ph.D, , [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT02203396
Organization ID
ATGIIT201401
Responsible Party
Sponsor-Investigator
Study Sponsor
Yizhou Zheng
Study Sponsor
Zheng Yizhou, M.D., Ph.D, Principal Investigator, Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Verification Date
May 2016