Aplastic AnemiaPhase 1/2NCT01105273
Human Leukocyte Antigen (HLA)-Haploidentical Hematopoietic Stem Cell Transplantation for Patients With Aplastic Anemia
A Phase 1/2 study testing anti-thymocyte globulin, filgrastim and Fludarabine in people with Aplastic Anemia, run by Asan Medical Center at 1 site in South Korea.
Trial summary
Rationale: Chemotherapy with fludarabine, cyclophosphamide and anti-thymocyte globulin 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
- Aplastic Anemia
- What is being tested?
- anti-thymocyte globulin, filgrastim and Fludarabine
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2009to Jul 2012
- Phase
- Phase 1/2
- 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.
About this study
Official title: HLA-haploidentical Allogeneic Hematopoietic Cell Transplantation Using CD3±CD19 Depletion for Patients With Aplastic Anemia After Conditioning of Fludarabine, Cyclophosphamide and Antithymocyte Globulin
Rationale: Chemotherapy with fludarabine, cyclophosphamide and anti-thymocyte globulin may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion CD3±CD19 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.
Purpose: This phase I/II trial is to evaluate the safety and efficacy of fludarabine, cyclophosphamide and antithymocyte globulin with CD3±CD19 depleted graft from haploidentical donors in treating patients with aplastic anemia.
- Conditions
- Aplastic Anemia
- Being tested
- anti-thymocyte globulin, filgrastim, Fludarabine, Cyclophosphamide, CD3±CD19 depleted hematopoietic stem cell transplantation
- Keywords
- Aplastic anemia, Fludarabine, CD3±CD19 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.
anti-thymocyte globulinBiological
On days -3 to -1
filgrastimBiological
Beginning on day 4 and continuing until blood counts recover
FludarabineDrug
30mg/M2 once daily IV on days -6 to -2
CyclophosphamideDrug
60 mg/kg IV on day-3 and -2
CD3±CD19 depleted hematopoietic stem cell transplantationProcedure or surgery
Immunogenetic depletion on CliniMACS
| Study group | Role | What they receive |
|---|---|---|
| HAPLO | Experimental | Not described Receives: Biological: anti-thymocyte globulin; Biological: filgrastim; Drug: Fludarabine; Drug: Cyclophosphamide; Procedure: CD3±CD19 depleted hematopoietic stem cell transplantation |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the engraftment rate and survival of CD3±CD19 depleted haploidentical peripheral blood stem cell transplantation after conditioning with fludarabine, cyclophosphamide and anti-thymocyte globulin.
Measured: 2 years post-transplant
Secondary outcomes (4)
To assess engraftment and graft failure
Number of patients who failed to engraft by 28 days.
Measured: 28 days post-transplant
To estimate the risk of acute GVHD
Number of patients with acute GVHD.
Measured: 100 days post-transplant
To assess treatment related mortality
Number of death after transplantation
Measured: 100 days post-transplant
To estimate overall survival
Measured: 1 year after transplantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Apr 2010 (estimated)
- Study startJul 2009
- Primary completionJul 2012
- Study completionJul 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
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
- NCT01105273
- Sponsor's protocol ID
- AMCPHO-SCT0802
- Status last verified
- Dec 2012
- First submitted
- 8 Apr 2010
- Last updated
- 3 Jan 2013
- Results posted
- No
Publications
Woodard P, Cunningham JM, Benaim E, Chen X, Hale G, Horwitz E, Houston J, Kasow K, Leung W, Wang W, Yusuf U, Handgretinger R. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant. 2004 Feb;33(4):411-8. doi: 10.1038/sj.bmt.1704358.
PubMed 14676782Kremens B, Basu O, Grosse-Wilde H, Sauerwein W, Schaefer UW, Havers W. Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype mismatched donor to a patient with severe aplastic anemia. Bone Marrow Transplant. 2001 Jan;27(1):111-3. doi: 10.1038/sj.bmt.1702748.
PubMed 11244448Lacerda JF, Martins C, Carmo JA, Lourenco F, Juncal C, Ismail S, Lacerda JM. Haploidentical stem cell transplantation with purified CD34+ cells after a chemotherapy-alone conditioning regimen in heavily transfused severe aplastic anemia. Biol Blood Marrow Transplant. 2005 May;11(5):399-400. doi: 10.1016/j.bbmt.2005.02.007. No abstract available.
PubMed 15846294Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, Balduzzi A, Owoc-Lempach J, Fagioli F, Or R, Peters C, Aversa F, Polge E, Dini G, Rocha V; Pediatric Diseases and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood. 2010 Apr 29;115(17):3437-46. doi: 10.1182/blood-2009-03-207001. Epub 2009 Dec 29.
PubMed 20040760Koh 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
- HLA-haploidentical Allogeneic Hematopoietic Cell Transplantation Using CD3±CD19 Depletion for Patients With Aplastic Anemia After Conditioning of Fludarabine, Cyclophosphamide and Antithymocyte Globulin
- ClinicalTrials.gov ID
- NCT01105273
- Acronym / sponsor ID
- AMCPHO-SCT0802
- Conditions
- Aplastic Anemia
- Keywords
- Aplastic anemia, Fludarabine, CD3±CD19 depletion, Haploidentical hematopoietic stem cell transplantation
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Asan Medical CenterUniversity, hospital or other
- Study start
- Jul 2009
- Primary completion
- Jul 2012 (actual)
- Study completion
- Jul 2012 (actual)
- First posted
- 16 Apr 2010 (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: Chemotherapy with fludarabine, cyclophosphamide and anti-thymocyte globulin may induce the engraftment cross the immunologic barrier in the setting of HLA-haploidentical allogeneic hematopoietic cell transplantation. In addition, depletion CD3±CD19 cells may contribute to prevent developing severe acute graft versus host disease (GVHD) in haploidentical transplantation.
Purpose: This phase I/II trial is to evaluate the safety and efficacy of fludarabine, cyclophosphamide and antithymocyte globulin with CD3±CD19 depleted graft from haploidentical donors in treating patients with aplastic anemia.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HAPLO | Experimental | Biological: anti-thymocyte globulin, Biological: filgrastim, Drug: Fludarabine, Drug: Cyclophosphamide, Procedure: CD3±CD19 depleted hematopoietic stem 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 |
|---|---|---|
| anti-thymocyte globulinOn days -3 to -1 | Biological | HAPLO |
| filgrastimBeginning on day 4 and continuing until blood counts recover | Biological | HAPLO |
| Fludarabine30mg/M2 once daily IV on days -6 to -2 | Drug | HAPLO |
| Cyclophosphamide60 mg/kg IV on day-3 and -2 | Drug | HAPLO |
| CD3±CD19 depleted hematopoietic stem cell transplantationImmunogenetic depletion on CliniMACS | Procedure or surgery | HAPLO |
Primary outcome
To assess the engraftment rate and survival of CD3±CD19 depleted haploidentical peripheral blood stem cell transplantation after conditioning with fludarabine, cyclophosphamide and anti-thymocyte globulin.
Time frame: 2 years post-transplant
4 secondary outcomes
To assess engraftment and graft failure
Time frame: 28 days post-transplant
To estimate the risk of acute GVHD
Time frame: 100 days post-transplant
To assess treatment related mortality
Time frame: 100 days post-transplant
To estimate overall survival
Time frame: 1 year after transplantation
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Jan 2013.
- Background: PubMed 14676782Woodard P, Cunningham JM, Benaim E, Chen X, Hale G, Horwitz E, Houston J, Kasow K, Leung W, Wang W, Yusuf U, Handgretinger R. Effective donor lymphohematopoietic reconstitution after haploidentical CD34+-selected hematopoietic stem cell transplantation in children with refractory severe aplastic anemia. Bone Marrow Transplant. 2004 Feb;33(4):411-8. doi: 10.1038/sj.bmt.1704358.
- Background: PubMed 11244448Kremens B, Basu O, Grosse-Wilde H, Sauerwein W, Schaefer UW, Havers W. Transplantation of CD34-enriched peripheral stem cells from an HLA-haplotype mismatched donor to a patient with severe aplastic anemia. Bone Marrow Transplant. 2001 Jan;27(1):111-3. doi: 10.1038/sj.bmt.1702748.
- Background: PubMed 15846294Lacerda JF, Martins C, Carmo JA, Lourenco F, Juncal C, Ismail S, Lacerda JM. Haploidentical stem cell transplantation with purified CD34+ cells after a chemotherapy-alone conditioning regimen in heavily transfused severe aplastic anemia. Biol Blood Marrow Transplant. 2005 May;11(5):399-400. doi: 10.1016/j.bbmt.2005.02.007. No abstract available.
- Background: PubMed 20040760Klingebiel T, Cornish J, Labopin M, Locatelli F, Darbyshire P, Handgretinger R, Balduzzi A, Owoc-Lempach J, Fagioli F, Or R, Peters C, Aversa F, Polge E, Dini G, Rocha V; Pediatric Diseases and Acute Leukemia Working Parties of the European Group for Blood and Marrow Transplantation (EBMT). Results and factors influencing outcome after fully haploidentical hematopoietic stem cell transplantation in children with very high-risk acute lymphoblastic leukemia: impact of center size: an analysis on behalf of the Acute Leukemia and Pediatric Disease Working Parties of the European Blood and Marrow Transplant group. Blood. 2010 Apr 29;115(17):3437-46. doi: 10.1182/blood-2009-03-207001. Epub 2009 Dec 29.
- 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 1/2 study testing anti-thymocyte globulin, filgrastim and Fludarabine in people with 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: finished, 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the engraftment rate and survival of CD3±CD19 depleted haploidentical peripheral blood stem cell transplantation after conditioning with fludarabine, cyclophosphamide and anti-thymocyte globulin. (time frame: 2 years post-transplant). 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 NCT01105273, which also lists 6 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.