Acquired Aplastic AnemiaPhase 2NCT01759732
Haploidentical Stem Cell Transplantation for Children With Acquired Severe Aplastic Anemia
A Phase 2 study testing Fludarabine, Cyclophosphamide and anti-thymocyte globulin in people with Acquired Aplastic Anemia, run by Asan Medical Center at 1 site in South Korea.
Trial summary
Rationale: Fludarabine, cyclophosphamide, anti-thymocyte globulin and low-dose total body irradiation (LD-TBI) may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Acquired Aplastic Anemia
- What is being tested?
- Fludarabine, Cyclophosphamide and anti-thymocyte globulin
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteSouth Korea
- Study dates
- Sep 2012to Dec 2015
- Phase
- Phase 2
- 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 Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria:
- Granulocyte count < 500/mm3,
- Corrected reticulocyte count < 1%,
- Platelet count < 20,000/mm3
- No HLA-identical family member or closely matched (8 of 8 HLA-locus match) unrelated marrow donor available
- HLA-haploidentical related donor available
Who cannot join
- Paroxysmal nocturnal hemoglobinuria or Fanconi anemia
- Clonal cytogenetic abnormalities or myelodysplastic syndromes
- Active fungal infections
- HIV positive
- Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure
- Pregnant or nursing
Trial locations and contacts
1 site in 1 country.
South Korea1 site, 1 recruiting
- Recruiting
Asan Medical Center
Seoul, 138-736
Ho Joon Im, MD, PhD, 82-2-3010-3371, hojim@amc.seoul.kr
Kyung Nam Koh, MD, PhD
About this study
Official title: Haploidentical Stem Cell Transplantation With Fixed Dose of T Cells After in Vitro T Cell Depletion Using CD3 Monoclonal Antibody for Children With Acquired Severe Aplastic Anemia
Rationale: Fludarabine, cyclophosphamide, anti-thymocyte globulin and low-dose total body irradiation (LD-TBI) may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion of CD3 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.
Purpose: Phase II trials to evaluate the efficacy of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia
- Conditions
- Acquired Aplastic Anemia
- Being tested
- Fludarabine, Cyclophosphamide, anti-thymocyte globulin, filgrastim, Total body irradiation
- Keywords
- Aplastic anemia, T cell dose, CD3 depletion, Haploidentical hematopoietic stem cell transplantation
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FludarabineDrug
40mg/M2 once daily IV on days -7 to -4
CyclophosphamideDrug
60 mg/kg IV on day-3 and -2
anti-thymocyte globulinBiological
filgrastimBiological
Also called Beginning on day 4 and continuing until blood counts recover
Total body irradiationRadiation
200 cGy per day on D-5 \& -4
CD3-depleted hematopoietic cell transplantationProcedure or surgery
Immunogenetic depletion on CliniMACS
| Study group | Role | What they receive |
|---|---|---|
| HAPLO | Experimental | Not described Receives: Drug: Fludarabine; Drug: Cyclophosphamide; Biological: anti-thymocyte globulin; Biological: filgrastim; Radiation: Total body irradiation; Procedure: CD3-depleted hematopoietic cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess engraftment rate and survival of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia
Measured: 2 years posttransplant
Secondary outcomes (4)
To assess engraftment and graft failure
Number of patients who failed to engraft by 28 days
Measured: 28 days posttransplant
To estimate the risk of acute GVHD
Number of patients with acute GVHD.
Measured: 100 days posttransplant
To assess treatment related mortality
Number of death after transplantation
Measured: 100 days posttransplant
To estimate overall survival and failure free survival
Measured: 1 year posttransplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jan 2013 (estimated)
- Study startSep 2012
- Primary completionDec 2014 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Acquired Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Asan Medical CenterThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Asan Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ho Joon Im, Asan Medical Center
- Investigators
- Ho Joon Im, MD, PhD, Principal investigator, Asan Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01759732
- Sponsor's protocol ID
- AMCPHO-SCT1202
- Status last verified
- Dec 2012
- First submitted
- 30 Dec 2012
- Last updated
- 3 Jan 2013
- Results posted
- No
Publications
Burroughs LM, Woolfrey AE, Storer BE, Deeg HJ, Flowers ME, Martin PJ, Carpenter PA, Doney K, Appelbaum FR, Sanders JE, Storb R. Success of allogeneic marrow transplantation for children with severe aplastic anaemia. Br J Haematol. 2012 Jul;158(1):120-8. doi: 10.1111/j.1365-2141.2012.09130.x. Epub 2012 Apr 26.
PubMed 22533862Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty JM, Adams RH, Ewell M, Leifer ES, Gersten ID, Carter SL, Horowitz MM, Nakamura R, Pulsipher MA, Difronzo NL, Confer DL, Eapen M, Anderlini P. Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biol Blood Marrow Transplant. 2012 Jul;18(7):1007-11. doi: 10.1016/j.bbmt.2012.04.014. Epub 2012 Apr 27.
PubMed 22546497Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Wang JZ, Huang XJ. A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transplant. 2012 Dec;47(12):1507-12. doi: 10.1038/bmt.2012.79. Epub 2012 May 28.
PubMed 22635243Koh KN, Im HJ, Kim BE, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. Br J Haematol. 2012 Apr;157(1):139-42. doi: 10.1111/j.1365-2141.2011.08924.x. Epub 2011 Nov 5. No abstract available.
PubMed 22055111Im HJ, Koh KN, Suh JK, Lee SW, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients. Bone Marrow Transplant. 2015 Feb;50(2):225-31. doi: 10.1038/bmt.2014.232. Epub 2014 Oct 13.
PubMed 25310303
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haploidentical Stem Cell Transplantation With Fixed Dose of T Cells After in Vitro T Cell Depletion Using CD3 Monoclonal Antibody for Children With Acquired Severe Aplastic Anemia
- ClinicalTrials.gov ID
- NCT01759732
- Acronym / sponsor ID
- AMCPHO-SCT1202
- Conditions
- Acquired Aplastic Anemia
- Keywords
- Aplastic anemia, T cell dose, CD3 depletion, Haploidentical hematopoietic stem cell transplantation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- Sep 2012
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 3 Jan 2013 (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.
Rationale: Fludarabine, cyclophosphamide, anti-thymocyte globulin and low-dose total body irradiation (LD-TBI) may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion of CD3 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.
Purpose: Phase II trials to evaluate the efficacy of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HAPLO | Experimental | Drug: Fludarabine, Drug: Cyclophosphamide, Biological: anti-thymocyte globulin, Biological: filgrastim, Radiation: Total body irradiation, Procedure: CD3-depleted hematopoietic cell transplantation |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Diagnosis of life-threatening marrow failure (severe aplastic anemia) of nonmalignant etiology meeting 2 of the following criteria:
- No HLA-identical family member or closely matched (8 of 8 HLA-locus match) unrelated marrow donor available
- HLA-haploidentical related donor available
Key exclusion criteria (6 listed)
- Paroxysmal nocturnal hemoglobinuria or Fanconi anemia
- Clonal cytogenetic abnormalities or myelodysplastic syndromes
- Active fungal infections
- HIV positive
- Severe disease other than aplastic anemia that would severely limit the probability of survival during the graft procedure
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 |
|---|---|---|
| Fludarabine40mg/M2 once daily IV on days -7 to -4 | Drug | HAPLO |
| Cyclophosphamide60 mg/kg IV on day-3 and -2 | Drug | HAPLO |
| anti-thymocyte globulin | Biological | HAPLO |
| filgrastimAlso: Beginning on day 4 and continuing until blood counts recover | Biological | HAPLO |
| Total body irradiation200 cGy per day on D-5 \& -4 | Radiation | HAPLO |
| CD3-depleted hematopoietic cell transplantationImmunogenetic depletion on CliniMACS | Procedure or surgery | HAPLO |
Primary outcome
To assess engraftment rate and survival of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia
Time frame: 2 years posttransplant
4 secondary outcomes
To assess engraftment and graft failure
Time frame: 28 days posttransplant
To estimate the risk of acute GVHD
Time frame: 100 days posttransplant
To assess treatment related mortality
Time frame: 100 days posttransplant
To estimate overall survival and failure free survival
Time frame: 1 year posttransplant
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2013.
- Background: PubMed 22533862Burroughs LM, Woolfrey AE, Storer BE, Deeg HJ, Flowers ME, Martin PJ, Carpenter PA, Doney K, Appelbaum FR, Sanders JE, Storb R. Success of allogeneic marrow transplantation for children with severe aplastic anaemia. Br J Haematol. 2012 Jul;158(1):120-8. doi: 10.1111/j.1365-2141.2012.09130.x. Epub 2012 Apr 26.
- Background: PubMed 22546497Tolar J, Deeg HJ, Arai S, Horwitz M, Antin JH, McCarty JM, Adams RH, Ewell M, Leifer ES, Gersten ID, Carter SL, Horowitz MM, Nakamura R, Pulsipher MA, Difronzo NL, Confer DL, Eapen M, Anderlini P. Fludarabine-based conditioning for marrow transplantation from unrelated donors in severe aplastic anemia: early results of a cyclophosphamide dose deescalation study show life-threatening adverse events at predefined cyclophosphamide dose levels. Biol Blood Marrow Transplant. 2012 Jul;18(7):1007-11. doi: 10.1016/j.bbmt.2012.04.014. Epub 2012 Apr 27.
- Background: PubMed 22635243Xu LP, Liu KY, Liu DH, Han W, Chen H, Chen YH, Zhang XH, Wang Y, Wang FR, Wang JZ, Huang XJ. A novel protocol for haploidentical hematopoietic SCT without in vitro T-cell depletion in the treatment of severe acquired aplastic anemia. Bone Marrow Transplant. 2012 Dec;47(12):1507-12. doi: 10.1038/bmt.2012.79. Epub 2012 May 28.
- Results publication: PubMed 22055111Koh KN, Im HJ, Kim BE, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Haploidentical haematopoietic stem cell transplantation using CD3 or CD3/CD19 depletion and conditioning with fludarabine, cyclophosphamide and antithymocyte globulin for acquired severe aplastic anaemia. Br J Haematol. 2012 Apr;157(1):139-42. doi: 10.1111/j.1365-2141.2011.08924.x. Epub 2011 Nov 5. No abstract available.
- Derived from this study: PubMed 25310303Im HJ, Koh KN, Suh JK, Lee SW, Choi ES, Jang S, Kwon SW, Park CJ, Seo JJ. Refinement of treatment strategies in ex vivo T-cell-depleted haploidentical SCT for pediatric patients. Bone Marrow Transplant. 2015 Feb;50(2):225-31. doi: 10.1038/bmt.2014.232. Epub 2014 Oct 13.
- AnemiaLink provided by the sponsor.
- FludarabineLink provided by the sponsor.
- CyclophosphamideLink provided by the sponsor.
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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.
Ho Joon Im, MD, PhD principal investigator
Asan Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Fludarabine, Cyclophosphamide and anti-thymocyte globulin in people with Acquired Aplastic Anemia, run by Asan Medical Center at 1 site in South Korea.
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 6 inclusion and 6 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 3 Jan 2013. 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 South Korea. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Ho Joon Im, MD, PhD (82-2-3010-3371, hojim@amc.seoul.kr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess engraftment rate and survival of haploidentical stem cell transplantation with fixed dose of T cells after in vitro T cell depletion using CD3 monoclonal antibody for children with acquired severe aplastic anemia (time frame: 2 years posttransplant). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01759732, which also lists 5 linked publications.
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 3 Jan 2013.