Brief Title
Comparison of Two Different Doses of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia
Official Title
Protocol for Comparison of Two Different Regimens of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia
Brief Summary
Acquired Aplastic anemia is one of the most frequent reason of bone marrow failure in East
(Pakistan).
- The first treatment option is Allogenic Bone Marrow transplantation which is an
expansive treatment option and also require a full matched HLA identical donor, hence
hardly 25% of our affected patients get opportunity for BMT.
- The second line treatment option caters a large chunk of patients (severe and non-severe
AA) along with those who lack HLA identical donor.
Previously many protocols had been used in past for ATG+CsA Treatment, this treatment
protocol especially addresses the two different regimens of ATG to study its efficacy,
durability and long-term effects. Following doses would be used:
- CsA+ATG @ 10mg/kg for 3 days
- CsA+ATG @ 10mg/kg for 5 days
Detailed Description
Aplastic Anaemia (AA) is characterized by pancytopenia with hypo-cellular bone marrow in the
absence of dysplasia, infiltration or fibrosis. The recommended first-line treatment options
include Allogenic Bone Marrow Transplantation with HLA matched sibling donor. However, due to
non-availability HLA matched identical sibling donor or due to other co-morbids and age,
second choice of treatment is Anti Thymocyte Globulin (ATG) and Cyclosporin (CsA).
Rabbit ATG (Fresenius) has never been tested for the treatment of aplastic anaemia in
Pakistani population before. We propose this investigator initiated trial which will will
compare two different protocols of Rabbit ATG-Fresenius, 10mg/kg for 3 days and 10mg/kg for 5
days along with CsA in Pakistani patients suffering from AA. The subjects will be Non-severe
(NSAA) and severe AA (SAA) who are not the eligible candidate for Allogenic Bone Marrow
Transplantation. Patients will be randomized into two equal arms with same biological
characteristics. Both arms will be treated with ATG-Fresenius and CsA in same doses with two
different duration of treatment. They will later continue with CsA for at least 12 months and
if response achieved, will be tapered more slowly over next 6 months.
The primary end point is to document the number of doses required by each of the two dose
schedule to produce a response, achieve a nadir absolute lymphocyte count of 200 cmm.
Secondary endpoints are short term safety of ATG-Fresenius, change in absolute neutrophil
count from the baseline in both arms, change in platelet count from the baseline, change in
absolute reticulocyte count, Number of blood units required till 8 weeks and 26 weeks, Number
of platelet doses required till 8 weeks and 26 weeks, relapse, response rates at 6 and 12
months, clonal evolution to PNH, myelodysplasia or acute leukaemia. Long-course CsA will be
assessed separately for its efficacy in reducing late events of relapse and evolution by
comparison to historical control data.
Study Type
Interventional
Primary Outcome
absolute blood counts not meeting the criteria of Aplastic Anemia
Secondary Outcome
transfusion dependency after ATG treatment
Condition
Aplastic Anemia
Intervention
ATG-fresenius
Study Arms / Comparison Groups
ATG-Fresenius 3 Days
Description: In one group Injection ATG-Fresenius will be given @ 10mg/kg will be given for 3 days along with Capsule Cyclosporin 5mg/kg for 6 months followed by very slow tapering of dose
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
60
Start Date
September 2013
Completion Date
December 2017
Primary Completion Date
December 2017
Eligibility Criteria
Inclusion Criteria:
i. Severe aplastic anemia characterized by: Bone marrow cellularity <30% (excluding
lymphocytes) AND
At least two of the following:
a. Absolute neutrophil count < 500/ uL b. Platelet count < 20,000/ uL c. Absolute
reticulocyte count <60,000/ uL i. Age > 2 years old ii. Weight > 9 kg
Exclusion Criteria:
i. Diagnosis of Fanconi's anemia ii. Evidence of a clonal disorder on cytogenetics.
Patients with very severe neutropenia (ANC < 200 /uL) will be excluded iii. Failure of BMT
iv. Prior immunosuppressive therapy with ATG, ALG, alemtuzumab, or high dose
cyclophosphamide v. Infection not adequately responding to appropriate therapy vi.
Serologic evidence of HIV infection vii. Failure to discontinue the herbal supplements or
Other alternative approach of treatment within 2 weeks of enrolment viii. 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 ix. History of carcinoma that is not
considered cured (except local cervical, basal cell, or squamous cell) x. Current
pregnancy, or unwillingness to take oral contraceptives or refrain from pregnancy if of
childbearing potential xi. Not able to understand the investigational nature of the study
or give informed consent
Gender
All
Ages
2 Years - 65 Years
Accepts Healthy Volunteers
No
Contacts
TAHIR S SHAMSI, MBBS,FRCPath, +923002581491, [email protected]
Location Countries
Pakistan
Location Countries
Pakistan
Administrative Informations
NCT ID
NCT02028416
Organization ID
NIBD2571975
Responsible Party
Principal Investigator
Study Sponsor
National Institute of Blood Disease Center, Pakistan
Study Sponsor
TAHIR S SHAMSI, MBBS,FRCPath, Principal Investigator, NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATION
Verification Date
April 2016