A Single-Arm Phase 2 Study With Optimized Standard Protocol for Severe Aplastic Anemia

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 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

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