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

NCT02203396 | Completed Phase 2 DMC

• 1 other identifier: IIT2014006
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Aplastic Anemia

Keywords

SAA; Immunosuppressive treatment; ATG; Cyclosporine; Levamisole

Outcome Measures

Primary Outcomes (1)

• 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).

  month +6

Secondary Outcomes (1)

• Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.

  month +12, month +60

Study Arms (1)

Severe Aplastic Anemia

EXPERIMENTAL

Drug: rabbit ATG, Cyclosporine, Levamisole

Drug: rabbit ATG, Cyclosporine, Levamisole

Interventions

rabbit ATG, Cyclosporine, Levamisole DRUG

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.

Also known as: rATG, CSA, LMS

Severe Aplastic Anemia

Eligibility Criteria

• Age: 6 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institute of Hematology & Blood Diseases Hospital, China: lead

Study Sites (1)

Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences

Tianjin, Tianjin Municipality, 300020, China

Location

Related Publications (2)

• 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.

  PMID: 12622583 RESULT

• 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.

  PMID: 1090310 RESULT

MeSH Terms

Conditions

Anemia, Aplastic

Interventions

thymoglobulin; Cyclosporine; Levamisole

Condition Hierarchy (Ancestors)

Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Failure Disorders; Bone Marrow Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins; Thiazoles; Sulfur Compounds; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Zheng Yizhou, M.D., Ph.D

  Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2014
• First Posted: July 29, 2014
• Study Start: August 1, 2014
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2017
• Last Updated: February 11, 2026

Record last verified: 2024-05

Locations

CN (1)