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

May 3, 2016 updated by: Yizhou Zheng
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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Anticipated)

40

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • China
    • Tianjin
      • TianJin, Tianjin, China, 300020
        • Recruiting
        • Institute of Hematology & Blood Diseases Hospital Chinese Academy of Medical Sciences
        • Contact:
        • Principal Investigator:
          • Zheng Yizhou, M.D., Ph.D

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

4 years to 68 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Severe Aplastic Anemia
Drug: rabbit ATG, Cyclosporine, Levamisole
Drug: rabbit ATG, Cyclosporine, Levamisole
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.
Other Names:
  • CSA
  • rATG
  • LMS

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
the response and complete remission rate with Optimized Standard Protocol.
Time Frame: month +6

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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Relapse rate, sustained response (SR), survival, and clonal evolution to myelodysplasia and acute leukemia.
Time Frame: month +12, month +60

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.
month +12, month +60

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Yizhou Zheng

Investigators

  • Principal Investigator: Zheng Yizhou, M.D., Ph.D, Anemia Therapeutic Center, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2014

Primary Completion (Anticipated)

September 1, 2016

Study Completion (Anticipated)

September 1, 2017

Study Registration Dates

First Submitted

July 27, 2014

First Submitted That Met QC Criteria

July 27, 2014

First Posted (Estimate)

July 29, 2014

Study Record Updates

Last Update Posted (Estimate)

May 4, 2016

Last Update Submitted That Met QC Criteria

May 3, 2016

Last Verified

May 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ATGIIT201401

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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