- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02028416
Comparison of Two Different Doses of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia (ATG)
Protocol for Comparison of Two Different Regimens of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia
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
Study Overview
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
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: MEHWESH TAJ, MBBS,FCPS
- Phone Number: +923002581491
- Email: mehweshfaisal@gmail.com
Study Contact Backup
- Name: Tahir S Shamsi, MBBS,FRCPath
- Phone Number: +9233452383956
- Email: shamsi@super.net.pk
Study Locations
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-
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Karachi, Pakistan, 75950
- Recruiting
- National Institute of Blood Diseases and Bone Marrow Transplantation
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Contact:
- MEHWESH TAJ, MBBS,FCPS
- Phone Number: +923002581491
- Email: mehweshfaisal@gmail.com
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Contact:
- TAHIR S SHAMSI, MBBS,FRCPath
- Phone Number: +923452383956
- Email: shamsi@super.net.pk
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Principal Investigator:
- TAHIR S SHAMSI, MBBS,FRCPath
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Sub-Investigator:
- MEHWESH TAJ, MBBS,FCPS
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Active Comparator: ATG-Fresenius 3 Days
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
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we will create 2 arms as per randomization table. Both arms will receive ATG-Fresenius but with 2 different regimens. the first arm will receive ATG-F @10mg/kg for 3 days and second arm will receive ATG-F same dose but for 5 days
Other Names:
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Experimental: ATG-Fresenius 5 Days
In other arm injection ATG will be given @10mg/Kg for 5 days (different dose regimen, according to the randomization) with capsule Cyclosporin@5mg/Kg (same dose) for 6 months followed by very slow tapering.
There is a difference of days of treatment received i-e 5 days.
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we will create 2 arms as per randomization table. Both arms will receive ATG-Fresenius but with 2 different regimens. the first arm will receive ATG-F @10mg/kg for 3 days and second arm will receive ATG-F same dose but for 5 days
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
absolute blood counts not meeting the criteria of Aplastic Anemia
Time Frame: 6 months
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Response is defined as blood counts no longer meeting the standard ("Camitta") criteria for severe pancytopenia in SAA, equivalent to 2 of the following values obtained on 2 serial blood count measurement at least one week apart at landmark time points (3, 6, and 12 months) . -To document the number of doses required by each of the two dose schedule to produce a rise in neutrophils and platelet count to achieve a nadir absolute lymphocyte count of 200 cmm Absolute neutrophil count > 500/ microL Platelet count > 20,000/ microL Reticulocyte count > 60,000/ microL |
6 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
transfusion dependency after ATG treatment
Time Frame: 2 years
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To document the short term safety of ATG-Fresenius at 8 weeks,12 weeks and then at 26 weeks in each arm
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2 years
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sustained improvement of blood counts post ATG
Time Frame: 2years
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To document the the change in absolute neutrophil, reticulocyte counts and platelet count from the baseline in each arm at 8 weeks, 12 weeks and then at 26 weeks
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2years
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short-term safety of ATG and clonal evolution
Time Frame: 26 weeks
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to document the short term safety of ATG and development of any clonal evolution to PNH, myelodysplasia or acute leukaemia in patient
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26 weeks
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response rates of ATG treatment
Time Frame: 2 years
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to document the response rates of treatment with ATG+ Cyclosporin in patients with non-severe and severe Aplastic anemia at 6,12 and 24 months
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2 years
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Collaborators and Investigators
Investigators
- Principal Investigator: TAHIR S SHAMSI, MBBS,FRCPath, National Institute of Blood Diseases and Bone Marrow Transplantation
- Study Director: MEHWESH TAJ, MBBS, FCPS, National Institute of Blood Diseases and Bone Marrow Transplantation
- Study Chair: UZMA RIZVI, MBBS, National Institute of Blood Diseases and Bone Marrow Transplantation
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- NIBD2571975
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
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