Back to resultsA Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia (OSP)
Primary Purpose
Aplastic Anemia
Status
Unknown status
Phase
Phase 2
Locations
China
Study Type
Interventional
Intervention
rabbit ATG, Cyclosporine, Levamisole
Sponsored by
About this trial
This is an interventional treatment trial for Aplastic Anemia focused on measuring SAA, Immunosuppressive treatment, ATG, Cyclosporine, Levamisole
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed SAA (according to the standard criteria)
- Bone marrow cellularity less than 30% (excluding lymphocytes)
- 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.
Sites / Locations
- Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical SciencesRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Severe Aplastic Anemia
Arm Description
Drug: rabbit ATG, Cyclosporine, Levamisole
Outcomes
Primary Outcome Measures
the response and complete remission rate with Optimized Standard Protocol.
Response will be evaluated at each clinic visit. Complete response (CR) was defined as achieving all three peripheral blood count criteria: (1) Hb level up to the normal range; (2) ANC≥1.5×109/L; (3) PLT≥100×109/L.
Partial response (PR) was defined as transfusion independent, no longer meeting criteria for severe disease. Persistence of transfusion requirement or death was evidence of no response (NR).
Secondary Outcome Measures
Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.
Relapse was defined as a responder who met criteria for SAA again after achieving response and keeping stable blood counts for at least 3 months.
Sustained response (SR) was defined as Hb > 10 g/dL at month +12 and +60, in the absence of any treatment.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02203396
Brief Title
A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia
Acronym
OSP
Official Title
A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Unknown status
Study Start Date
August 2014 (undefined)
Primary Completion Date
September 2016 (Anticipated)
Study Completion Date
September 2017 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Yizhou Zheng
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Aplastic Anemia
Keywords
SAA, Immunosuppressive treatment, ATG, Cyclosporine, Levamisole
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Severe Aplastic Anemia
Arm Type
Experimental
Arm Description
Drug: rabbit ATG, Cyclosporine, Levamisole
Intervention Type
Drug
Intervention Name(s)
rabbit ATG, Cyclosporine, Levamisole
Other Intervention Name(s)
rATG, CSA, LMS
Intervention Description
rATG is administered at a dose of 1.97 mg/kg/day for 9 days CSA is administered orally at a dose of 3 mg/kg qod Levamisole is administered orally at a dose of 2.5 mg/kg qod. The CSA and LMS is designed to alternately every other day.
Primary Outcome Measure Information:
Title
the response and complete remission rate with Optimized Standard Protocol.
Description
Response will be evaluated at each clinic visit. Complete response (CR) was defined as achieving all three peripheral blood count criteria: (1) Hb level up to the normal range; (2) ANC≥1.5×109/L; (3) PLT≥100×109/L.
Partial response (PR) was defined as transfusion independent, no longer meeting criteria for severe disease. Persistence of transfusion requirement or death was evidence of no response (NR).
Time Frame
month +6
Secondary Outcome Measure Information:
Title
Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.
Description
Relapse was defined as a responder who met criteria for SAA again after achieving response and keeping stable blood counts for at least 3 months.
Sustained response (SR) was defined as Hb > 10 g/dL at month +12 and +60, in the absence of any treatment.
Time Frame
month +12, month +60
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Newly diagnosed SAA (according to the standard criteria)
Bone marrow cellularity less than 30% (excluding lymphocytes)
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nie Neng
Email
docnn@163.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Zheng Yizhou, M.D., Ph.D
Organizational Affiliation
Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
Official's Role
Principal Investigator
Facility Information:
Facility Name
Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences
City
TianJin
State/Province
Tianjin
ZIP/Postal Code
300020
Country
China
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nie Neng
Phone
+86 22 23909023
Email
docnn@163.com
First Name & Middle Initial & Last Name & Degree
Zheng Yizhou, M.D., Ph.D
12. IPD Sharing Statement
Citations:
PubMed Identifier
12622583
Citation
Rosenfeld S, Follmann D, Nunez O, Young NS. Antithymocyte globulin and cyclosporine for severe aplastic anemia: association between hematologic response and long-term outcome. JAMA. 2003 Mar 5;289(9):1130-5. doi: 10.1001/jama.289.9.1130.
Results Reference
result
PubMed Identifier
1090310
Citation
Camitta BM, Rappeport JM, Parkman R, Nathan DG. Selection of patients for bone marrow transplantation in severe aplastic anemia. Blood. 1975 Mar;45(3):355-63.
Results Reference
result
Learn more about this trial
A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia
We'll reach out to this number within 24 hrs