Aplastic AnemiaATGNCT02028416
Comparison of Two Different Doses of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia
A study testing ATG-fresenius in people with Aplastic Anemia, run by National Institute of Blood Disease Center, Pakistan at 1 site in Pakistan.
Trial 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… Read more about this study
- Who is it for?
- Ages 2 to 65 years
- Conditions the study is for
- Aplastic Anemia
- What is being tested?
- ATG-fresenius
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 sitePakistan
- Study dates
- Sep 2013to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Severe aplastic anemia characterized by: Bone marrow cellularity <30% (excluding lymphocytes) AND
- At least two of the following:
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
Pakistan1 site, 1 recruiting
- Recruiting
National Institute of Blood Diseases and Bone Marrow Transplantation
Karachi, Pakistan, 75950
MEHWESH TAJ, MBBS,FCPS, +923002581491, mehweshfaisal@gmail.com
TAHIR S SHAMSI, MBBS,FRCPath, +923452383956, shamsi@super.net.pk
About this study
Official title: 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.
Read more
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
Read the 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.
- Conditions
- Aplastic Anemia
- Being tested
- ATG-fresenius
- Keywords
- pancytopenia, aplastic anemia, ATG, Cyclosporin
- Medical subject headings
- Anemia, Aplastic, Pancytopenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATG-freseniusDrug
Also called Rabbit ATG, ATG-F
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
| Study group | Role | What they receive |
|---|---|---|
| ATG-Fresenius 3 Days | Active comparator | 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 Receives: Drug: ATG-fresenius |
| ATG-Fresenius 5 Days | Experimental | 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. Receives: Drug: ATG-fresenius |
What is being measured
The primary outcome is the main question the study is designed to answer.
absolute blood counts not meeting the criteria of Aplastic Anemia
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
Measured: 6 months
Secondary outcomes (4)
transfusion dependency after ATG treatment
To document the short term safety of ATG-Fresenius at 8 weeks,12 weeks and then at 26 weeks in each arm
- Number of blood units required till 8 weeks and 26 weeks
- Number of platelet doses required till 8 weeks and 26 weeks
Measured: 2 years
sustained improvement of blood counts post ATG
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
Measured: 2years
short-term safety of ATG and clonal evolution
to document the short term safety of ATG and development of any clonal evolution to PNH, myelodysplasia or acute leukaemia in patient
Measured: 26 weeks
response rates of ATG treatment
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
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jan 2014 (estimated)
- Study startSep 2013
- Primary completionDec 2017 (estimated)
- Study completionDec 2017 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Aplastic AnemiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- National Institute of Blood Disease Center, Pakistan
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, MEHWESH TAJ, National Institute of Blood Disease Center, Pakistan
- Investigators
- TAHIR S SHAMSI, MBBS,FRCPath, Principal investigator, NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATIONMEHWESH TAJ, MBBS, FCPS, Study director, NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATIONUZMA RIZVI, MBBS, Study chair, NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATION
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02028416
- Sponsor's protocol ID
- NIBD2571975
- Acronym
- ATG
- Status last verified
- Apr 2016
- First submitted
- 2 Jan 2014
- Last updated
- 5 Apr 2016
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No: All data saved at research department of NIBD under supervision of PI
Study at a glance
From the registry record, last updated by the sponsor on 5 Apr 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Protocol for Comparison of Two Different Regimens of Rabbit ATG-Fresenius With Cyclosporin in the Treatment of Acquired Aplastic Anaemia
- ClinicalTrials.gov ID
- NCT02028416
- Acronym / sponsor ID
- ATG / NIBD2571975
- Conditions
- Aplastic Anemia
- Keywords
- pancytopenia, aplastic anemia, ATG, Cyclosporin
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- National Institute of Blood Disease Center, PakistanUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Dec 2017 (estimated)
- Study completion
- Dec 2017 (estimated)
- First posted
- 7 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATG-Fresenius 3 Days | Active comparator | Drug: ATG-freseniusIn 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 |
| ATG-Fresenius 5 Days | Experimental | Drug: ATG-freseniusIn 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. |
Who may qualify
- Ages
- 2 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Severe aplastic anemia characterized by: Bone marrow cellularity <30% (excluding lymphocytes) AND
- 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
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATG-freseniusAlso: Rabbit ATG, ATG-Fwe 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 | Drug | ATG-Fresenius 3 Days, ATG-Fresenius 5 Days |
Primary outcome
absolute blood counts not meeting the criteria of Aplastic Anemia
Time frame: 6 months
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
4 secondary outcomes
transfusion dependency after ATG treatment
Time frame: 2 years
sustained improvement of blood counts post ATG
Time frame: 2years
short-term safety of ATG and clonal evolution
Time frame: 26 weeks
response rates of ATG treatment
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2016.
- Individual participant dataSharing planned: No. All data saved at research department of NIBD under supervision of PI
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
TAHIR S SHAMSI, MBBS,FRCPath principal investigator
NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATION
MEHWESH TAJ, MBBS, FCPS study director
NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATION
UZMA RIZVI, MBBS study chair
NATIONAL INSTITUTE OF BLOOD DISEASES AND BONE MARROW TRANSPLANTATION
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ATG-fresenius in people with Aplastic Anemia, run by National Institute of Blood Disease Center, Pakistan at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 5 Apr 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Mehwesh Taj, MBBS,FCPS (+923002581491, mehweshfaisal@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
absolute blood counts not meeting the criteria of Aplastic Anemia (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2016.