Clinical trial NCT02203396: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Aplastic Anemia
Keywords: SAA
Immunosuppressive treatment
ATG
Cyclosporine
Levamisole
Lead sponsor: Institute of Hematology & Blood Diseases Hospital, China
Sponsor class: OTHER
First posted: 2014-07-29
Enrollment: 40
Sex: ALL
Minimum age (years): 6
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: the response and complete remission rate with Optimized Standard Protocol.
timeFrame: month +6
Secondary outcomes:
measure: Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.
timeFrame: month +12, month +60
Other outcomes:
Locations:
city: TianJin
country: China
facility: Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences
state: Tianjin
Study officials:
affiliation: Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences
name: Zheng Yizhou, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.