Wiskott-Aldrich SyndromePhase 1/2NCT00885833
Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome (WAS)
A Phase 1/2 study testing Fludarabine, Busulfan, Thymoglobulin in people with Wiskott-Aldrich Syndrome, run by The Korean Society of Pediatric Hematology Oncology at 1 site in South Korea.
Trial summary
Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immune-deficiency syndrome and hematopoietic stem cell transplantation (HSCT) has become a curative modality. But the transplant with the conventional conditioning resulted in high incidence of treatment related toxicities and non-myeloablative conditioning… Read more about this study
- Who is it for?
- Ages 1 year to 25 years
- Conditions the study is for
- Wiskott-Aldrich Syndrome
- What is being tested?
- Fludarabine, Busulfan, Thymoglobulin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteSouth Korea
- Study dates
- Feb 2007to Mar 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 1 year to 25 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of Wiskott-Aldrich syndrome with gene analysis.
- Indicated for hematopoietic stem cell transplantation.
- Age: no limitation.
- Performance status: ECOG 0-2.
- Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases:
- Heart: a shortening fraction > 30%, ejection fraction > 45%.
Show all 11Show fewer
- Liver: total bilirubin < 2 × upper limit of normal; ALT < 3 × upper limit of normal.
- Kidney: creatinine <2 × normal or a creatinine clearance (GFR) > 60 ml/min/1.73m2.
- Patients must lack any active viral infections or active fungal infection.
- Appropriate hematopoietic stem cell donor is available.
- Patients (or one of parents if patients age < 19) should sign informed consent.
Who cannot join
- Pregnant or nursing women.
- Malignant (except acute myeloid leukemia) or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
- Psychiatric disorder that would preclude compliance.
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Seoul National University Hospital
Seoul, Chongno-gu, 110-744
About this study
Official title: Phase I/II Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome
Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immune-deficiency syndrome and hematopoietic stem cell transplantation (HSCT) has become a curative modality. But the transplant with the conventional conditioning resulted in high incidence of treatment related toxicities and non-myeloablative conditioning resulted in high incidence of engraftment failure. Recently, fludarabine based reduced toxicity myeloablative conditioning regimen was developed for adult myeloid malignancies with promising result of good engraftment and low treatment related toxicities. To increase the engraftment potential without serious complication, reduced toxicity myeloablative conditioning regimen composed of fludarabine, busulfan, and thymoglobulin is designed for Wiskott-Aldrich syndrome.
Read the detailed description
Wiskott-Aldrich syndrome (WAS) is an rare X-linked congenital immune-deficiency syndrome characterized by the triad of recurrent infection, eczema and thrombocytopenia with small size of platelet (Puck JM, 2006). Clinical studies revealed high rate of autoimmune disorder and malignancy in WAS (Ochs HD, 2006). The identification of the molecular defect in 1994 (Derry JM, 1994) has broadened the clinical spectrum of the syndrome to include chronic or intermittent X-linked thrombocytopenia (XLT), a relatively mild form of WAS and X-lined neutropenia caused by an arrest of myelopoiesis (Ochs HD, 2006).
The incidence of WAS in Korea was very low and only 6 patients diagnosed between 2001 and 2005 (Kim JG, 2006).
Conventional treatments for WAS such as prophylactic antibiotics and immune globin for infection and platelet transfusion for bleeding were not so successful (Thrasher AJ, 2000). Bone marrow transplantation (BMT) from an HLA-matched related donor is an effective treatment (Filipovich AH, 2001) and patients without appropriate related donor could receive alternative stem cell source such as matched unrelated donor or cord blood. But the transplant with the alternative donor needed more intensive conditioning to overcome the hematologic and immunologic barrier with increased treatment related toxicity. Further progress depends in particular on the development of alternative preparative conditioning regimens which allow stable engraftment of donor precursor cells with minimal systemic toxic side effects (Friedrich W, 2004).
Recently, we reported successful unrelated bone marrow transplantation in a boy with WAS with reduced toxicity myeloablative conditioning regimen to increase the engraftment potential without serious complication (Kang, 2008), and extended to multicenter phase I/II pilot study with this reduced toxicity myeloablative conditioning regimen in the HSCT for WAS.
- Conditions
- Wiskott-Aldrich Syndrome
- Being tested
- Fludarabine, Busulfan, Thymoglobulin
- Keywords
- Wiskott-Aldrich syndrome, HSCT
- Medical subject headings
- Wiskott-Aldrich Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Fludarabine, Busulfan, ThymoglobulinDrug
fludarabine (40 mg/m2 once daily i.v. on days -8, -7, -6, -5, -4 \& -3) busulfan (0.8 mg/kg every 6 hours i.v. on days -6, -5, -4, \& -3) thymoglobulin (2.5 mg/kg once daily i.v. on days -8, -7, -6 for cord blood and on days -4, -3, -2 for bone marrow or mobilized peripheral blood)
| Study group | Role | What they receive |
|---|---|---|
| Fludarabine | Experimental | Not described Receives: Drug: Fludarabine, Busulfan, Thymoglobulin |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS.
Measured: Feb. 2007 to Jan. 2012
To evaluate the incidence and severity of toxicity and treatment related mortality.
Measured: Feb. 2007 to Jan. 2012
Secondary outcomes (3)
To evaluate overall and event free survival rate.
Measured: Feb. 2007 to Jan. 2012
To evaluate acute and chronic graft versus host disease (GVHD).
Measured: Feb. 2007 to Jan. 2012
To evaluate immunologic recovery after HSCT.
Measured: Feb. 2007 to Jan. 2012
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2009 (estimated)
- Study startFeb 2007
- Primary completionMar 2012
- Study completionMar 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Wiskott-Aldrich SyndromeStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Korean Society of Pediatric Hematology Oncology
- Sponsor type
- Research network
- Investigators
- Hyo Seop Ahn, Ph. D, Principal investigator, The Korean Society of Pediatric Hematology Oncology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00885833
- Sponsor's protocol ID
- KSPHO-S0701
- Status last verified
- Jul 2014
- First submitted
- 21 Apr 2009
- Last updated
- 14 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of Reduced Toxicity Myeloablative Conditioning Regimen for Wiskott-Aldrich Syndrome
- ClinicalTrials.gov ID
- NCT00885833
- Acronym / sponsor ID
- KSPHO-S0701
- Conditions
- Wiskott-Aldrich Syndrome
- Keywords
- Wiskott-Aldrich syndrome, HSCT
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (estimated)
- Lead sponsor
- The Korean Society of Pediatric Hematology OncologyResearch network
- Study start
- Feb 2007
- Primary completion
- Mar 2012 (actual)
- Study completion
- Mar 2012 (actual)
- First posted
- 22 Apr 2009 (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.
Wiskott-Aldrich syndrome (WAS) is a rare X-linked congenital immune-deficiency syndrome and hematopoietic stem cell transplantation (HSCT) has become a curative modality. But the transplant with the conventional conditioning resulted in high incidence of treatment related toxicities and non-myeloablative conditioning resulted in high incidence of engraftment failure. Recently, fludarabine based reduced toxicity myeloablative conditioning regimen was developed for adult myeloid malignancies with promising result of good engraftment and low treatment related toxicities. To increase the engraftment potential without serious complication, reduced toxicity myeloablative conditioning regimen composed of fludarabine, busulfan, and thymoglobulin is designed for Wiskott-Aldrich syndrome.
Detailed description
Wiskott-Aldrich syndrome (WAS) is an rare X-linked congenital immune-deficiency syndrome characterized by the triad of recurrent infection, eczema and thrombocytopenia with small size of platelet (Puck JM, 2006). Clinical studies revealed high rate of autoimmune disorder and malignancy in WAS (Ochs HD, 2006). The identification of the molecular defect in 1994 (Derry JM, 1994) has broadened the clinical spectrum of the syndrome to include chronic or intermittent X-linked thrombocytopenia (XLT), a relatively mild form of WAS and X-lined neutropenia caused by an arrest of myelopoiesis (Ochs HD, 2006).
The incidence of WAS in Korea was very low and only 6 patients diagnosed between 2001 and 2005 (Kim JG, 2006).
Conventional treatments for WAS such as prophylactic antibiotics and immune globin for infection and platelet transfusion for bleeding were not so successful (Thrasher AJ, 2000). Bone marrow transplantation (BMT) from an HLA-matched related donor is an effective treatment (Filipovich AH, 2001) and patients without appropriate related donor could receive alternative stem cell source such as matched unrelated donor or cord blood. But the transplant with the alternative donor needed more intensive conditioning to overcome the hematologic and immunologic barrier with increased treatment related toxicity. Further progress depends in particular on the development of alternative preparative conditioning regimens which allow stable engraftment of donor precursor cells with minimal systemic toxic side effects (Friedrich W, 2004).
Recently, we reported successful unrelated bone marrow transplantation in a boy with WAS with reduced toxicity myeloablative conditioning regimen to increase the engraftment potential without serious complication (Kang, 2008), and extended to multicenter phase I/II pilot study with this reduced toxicity myeloablative conditioning regimen in the HSCT for WAS.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Fludarabine | Experimental | Drug: Fludarabine, Busulfan, Thymoglobulin |
Who may qualify
- Ages
- 1 year to 25 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (11 listed)
- Diagnosis of Wiskott-Aldrich syndrome with gene analysis.
- Indicated for hematopoietic stem cell transplantation.
- Age: no limitation.
- Performance status: ECOG 0-2.
- Patients must be free of significant functional deficits in major organs, but the following eligibility criteria may be modified in individual cases:
Key exclusion criteria (3 listed)
- Pregnant or nursing women.
- Malignant (except acute myeloid leukemia) or nonmalignant illness that is uncontrolled or whose control may be jeopardized by complications of study therapy.
- Psychiatric disorder that would preclude compliance.
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 |
|---|---|---|
| Fludarabine, Busulfan, Thymoglobulinfludarabine (40 mg/m2 once daily i.v. on days -8, -7, -6, -5, -4 \& -3) busulfan (0.8 mg/kg every 6 hours i.v. on days -6, -5, -4, \& -3) thymoglobulin (2.5 mg/kg once daily i.v. on days -8, -7, -6 for cord blood and on days -4, -3, -2 for bone marrow or mobilized peripheral blood) | Drug | Fludarabine |
Primary outcome
To evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS.
Time frame: Feb. 2007 to Jan. 2012
To evaluate the incidence and severity of toxicity and treatment related mortality.
Time frame: Feb. 2007 to Jan. 2012
3 secondary outcomes
To evaluate overall and event free survival rate.
Time frame: Feb. 2007 to Jan. 2012
To evaluate acute and chronic graft versus host disease (GVHD).
Time frame: Feb. 2007 to Jan. 2012
To evaluate immunologic recovery after HSCT.
Time frame: Feb. 2007 to Jan. 2012
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 14 Jul 2014.
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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.
Hyo Seop Ahn, Ph. D principal investigator
The Korean Society of Pediatric Hematology Oncology
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 Fludarabine, Busulfan, Thymoglobulin in people with Wiskott-Aldrich Syndrome, run by The Korean Society of Pediatric Hematology Oncology 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 11 inclusion and 3 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 14 Jul 2014. 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 evaluate the engraftment potential of fludarabine, busulfan plus thymoglobulin conditioning regimen for HSCT in WAS. (time frame: Feb. 2007 to Jan. 2012). The study lists 2 primary outcomes in all. 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 14 Jul 2014.