Idiopathic Aplastic AnemiaPhase 2UPFRONT-MUDNCT05419843
Up-front Matched Unrelated Donor Transplantation in Pediatric Patients With Idiopathic Aplastic Anemia
A Phase 2 study testing HSCT Arm group in people with Idiopathic Aplastic Anemia and Severe Aplastic Anemia, run by Assistance Publique - Hôpitaux de Paris.
Trial summary
Pediatric patients with idiopathic aplastic anemia (AA) respond better than adults to immunosuppressive therapy (IST) but the long-term risks of relapse, ciclosporine dependence, and clonal evolution are high. UK investigators reported a 5-year estimated failure-free survival (FFS) after IST of 13.3%. Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Idiopathic Aplastic Anemia, Severe Aplastic Anemia, Moderate Aplastic Anemia Requiring Transfusions
- What is being tested?
- HSCT Arm group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- No sites listed yet
- Study dates
- Jun 2022to Jun 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- age<18years old
- Pediatric patients aged less than 18 years with idiopathic aplastic anemia and an indication for treatment (severe aplastic anemia or moderate aplastic anemia requiring transfusions)
- With a good probability to have a HLA-10/10 matched unrelated donor available (the patient needs to have at least 3 MUD identified within the book BMDW (Bone Marrow Donors Worldwide) or using the easy match software to be included)
- With usual criteria for allo-SCT:
- Lansky >70% for those below 16 years and Karnofsky > 70% for those above 16 years
- No severe and uncontrolled infection
Show all 14Show fewer
- Adequate organ function: ASAT and ALAT ≤ 5N*, total bilirubin ≤ 2N, creatinine clearance > 70% of higher normal values for age.
- With health insurance coverage
- Contraception methods** for young girl and men of childbearing age must be prescribed during all the duration of the research.
- Parents having read and understand the information note and signed a written informed consent (the patient's agreement depending on his age will be sought)
- because typical presentation of aplastic anemia post-hepatitis
- NB : The authorized contraceptive methods are:
- For women of childbearing age and in absence of permanent sterilization: oral, intravaginal or transdermal combined hormonal contraception, oral, injectable or transdermal progestogen-only hormonal contraception, intrauterine hormonal-releasing system (IUS).
- For man in absence of permanent sterilization: condoms
Who cannot join
- Patients :
- With a matched related donor available
- With uncontrolled infection
- With seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR HBV or HCV and associated hepatic cytolysis
- Renal failure with creatinine clearance below 70% of higher normal values for age
- Pregnant (βHCG positive) or breast-feeding
Show all 12Show fewer
- With Heart failure according to NYHA (II or more)
- Preexisting acute hemorrhagic cystitis
- Urinary tract obstruction
- Yellow fever vaccine within 2 months before transplantation
- Who have any debilitating medical or psychiatric illness, which preclude understanding the inform consent as well as optimal treatment and follow-up (depending of his age and understanding).
- With Contraindication to treatments used during the research
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Up-front Matched Unrelated Donor Transplantation in Pediatric Patients With Idiopathic Aplastic Anemia: a Phase II Feasibility Study
Pediatric patients with idiopathic aplastic anemia (AA) respond better than adults to immunosuppressive therapy (IST) but the long-term risks of relapse, ciclosporine dependence, and clonal evolution are high. UK investigators reported a 5-year estimated failure-free survival (FFS) after IST of 13.3%. In contrast, in 44 successive children who received a matched unrelated donor (MUD), hematopoietic stem cell transplantation (HSCT), there was an excellent estimated 5-year FFS of 95%. Forty of these children had previously failed IST. Because of those excellent results, up-front fully matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) became an attractive first-line option. In 2005 to 2014, a UK cohort of 29 children with idiopathic AA thus received MUD HSCTs as first-line therapy (they did not receive IST prior to HSCT). Results were excellent, with low Graft versus Host Disease rates and only 1 death (idiopathic pneumonia). This cohort was then compared with historical matched controls, transplanted or not. Outcomes for the up-front unrelated cohort HSCT were similar to Matched Related Donor HSCT and superior to IST and unrelated HSCT post-IST failure. Since then, many investigators are offering up-front MUD HSCT in pediatric patients worldwide. However, those results should be treated with extreme caution: 1) the design is retrospective; 2) the excellent up-front MUD HSCT may arise from the use of alemtuzumab in the conditioning regimen (alemtuzumab is not easily available worldwide) and 3) there was no formal quality-of-life assessment. Moreover, this strategy is highly dependent on donor identification (Caucasian patients have the highest likelihood of having a MUD) and donor not eventually receive HSCT because of the risk of infections/complications caused by unexpected donor delays or cancellation. Prospective trials are thus urgently needed to address the feasibility of such procedure, in term of timing (delay to offer MUD HSCT) and conditioning regimen (nothing is known of the use of other regimens, non alemtuzumab-based, in this setting).
The main objective of this Two-Stage Phase 2 multicenter study is to realize up-front HSCT within 2 months once a MUD has been identified.
- Conditions
- Idiopathic Aplastic Anemia, Severe Aplastic Anemia, Moderate Aplastic Anemia Requiring Transfusions
- Being tested
- HSCT Arm group
- Medical subject headings
- Anemia, Aplastic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HSCT Arm groupOther
Conditioning regimen Stem cell source Only Bone Marrow With a minimal target dose of 4x108 nucleated cells/kg recipient ideal body weight. If the graft is less rich than the minimum target dose, it can be administered at the discretion to the physician.
GVHD Prophylaxis Prevention of EBV reactivation : Rituximab 150mg/m2 IV at Day+5 post HSCT.
| Study group | Role | What they receive |
|---|---|---|
| HSCT arm group | Experimental | 1. Conditioning regimen
2. Stem cell source Only Bone Marrow With a minimal target dose of 4x108 nucleated cells/kg recipient ideal body weight. If the graft is less rich than the minimum target dose, it can be administered at the discretion to the physician.
3. GVHD Prophylaxis
4. Prevention of EBV reactivation : Rituximab 150mg/m2 IV at Day+5 post HSCT. Receives: Other: HSCT Arm group |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with upfront matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) effectively performed
Proportion of patients with upfront matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) effectively performed in the first two months after unrelated donor search.
Measured: within 2 months (60 days) after identification of a MUD
Secondary outcomes (47)
Graft failure incidence
Measured: up to 24 months
Neutrophils engraftment
Neutrophils engraftment will be defined as first day of 3 consecutive days with neutrophils >0.5 G/L
Measured: at day 100
Platelets engraftment
Platelets engraftment will be defined as first day of 7 consecutive days with platelets >20 G/L
Measured: at day 100
Absolute number of neutrophils
Measured: at 1 month
Absolute number of neutrophils
Measured: at 2 months
Absolute number of neutrophils
Measured: at 3 months
Absolute number of neutrophils
Measured: at 6 months
Absolute number of neutrophils
Measured: at 12 months
Absolute number of neutrophils
Measured: at day of last platelet and red blood cell transfusions (assessed up to 24 months)
Absolute numbers of platelets
Measured: at 1 month
Absolute numbers of platelets
Measured: at 2 months
Absolute numbers of platelets
Measured: at 3 months
Absolute numbers of platelets
Measured: at 6 months
Absolute numbers of platelets
Measured: at 12 months
Absolute numbers of platelets
Measured: up to 24 months
Acute GvHD incidence
Measured: at month 3
Chronic GvHD incidence
Measured: at 24 months
Relapse incidence
Measured: at 12 months
Relapse incidence
Measured: at 24 months
Progression free survival
Measured: at 12 months
Progression free survival
Measured: at 24 months
Incidence of CMV infection
Measured: at 12 months
Incidence of EBV infection
Measured: at 12 months
Incidence of severe infections
Severe infections will be defined as CTACE grade 3-4
Measured: at 3 months
Incidence of severe infections
Severe infections will be defined as CTACE grade 3-4
Measured: at 6 months
Incidence of severe infections
Severe infections will be defined as CTACE grade 3-4
Measured: at 12 months
Incidence of severe infections
Severe infections will be defined as CTACE grade 3-4
Measured: at 24 months
Non-relapse mortality
Measured: at 24 months
Overall survival
Measured: at 24 months
Quality of life questionnaires PedsQL
Quality of life will be evaluated using PedsQL questionnaire. Scores varies from 0 to100, with higher scores associated with better health-related quality of life.
Measured: at inclusion
Quality of life questionnaires PedsQL
Quality of life will be evaluated using PedQQL questionnaire.Higher scores associated with better health-related quality of life. Scores varies from 0 to100, with higher scores associated with better health-related quality of life.
Measured: at 1 month
Quality of life questionnaires PedsQL
Quality of life will be evaluated using PedQQL questionnaire.Higher scores associated with better health-related quality of life. Scores varies from 0 to100, with higher scores associated with better health-related quality of life.
Measured: at 3 months
Quality of life questionnaires PedsQL
Quality of life will be evaluated using PedsQL questionnaire. Higher scores associated with better health-related quality of life. Scores varies from 0 to100, with higher scores associated with better health-related quality of life.
Measured: at 6 months
Quality of life questionnaires PedsQL
Quality of life will be evaluated using PedsQL questionnaire.Scores varies from 0 to100, with higher scores associated with better health-related quality of life.
Measured: at 12 months
Quality of life questionnaires PedsQL
Quality of life will be evaluated using PedsQL questionnaire.Scores varies from 0 to100, with higher scores associated with better health-related quality of life.
Measured: at 24 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 1 month
Proportion of patients with a donor chimerism of 90% or more
Measured: at 3 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 6 months
Proportion of patients with a donor chimerism of 90% or more
Measured: at 12 months
Immune reconstitution
Immune reconstitution will be done by analyzing T, B, NK, regulatory T cell levels in the peripheral blood. All have the same unit measure namely absolute numbers/microL
Measured: at 3 months
Immune reconstitution
Immune reconstitution will be done by analyzing T, B, NK, regulatory T cell levels in the peripheral blood. All have the same unit measure namely absolute numbers/microL
Measured: at 6 months
Immune reconstitution
Immune reconstitution will be done by analyzing T, B, NK, regulatory T cell levels in the peripheral blood. All have the same unit measure namely absolute numbers/microL.
Measured: at 12 months
Immune reconstitution
Immune reconstitution will be done by analyzing T, B, NK, regulatory T cell levels in the peripheral blood. All have the same unit measure namely absolute numbers/microL.
Measured: at 24 months
Ferritin levels
Measured: at 3 months
Ferritin levels
Measured: at 6 months
Ferritin levels
Measured: at 12 months
Ferritin levels
Measured: at 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2022
- Study startJun 2022 (estimated)
- Primary completionAug 2025 (estimated)
- Study completionJun 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Idiopathic Aplastic AnemiaStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05419843
- Sponsor's protocol ID
- APHP 200005
- Acronym
- UPFRONT-MUD
- Status last verified
- May 2022
- First submitted
- 23 May 2022
- Last updated
- 15 Jun 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jun 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Up-front Matched Unrelated Donor Transplantation in Pediatric Patients With Idiopathic Aplastic Anemia: a Phase II Feasibility Study
- ClinicalTrials.gov ID
- NCT05419843
- Acronym / sponsor ID
- UPFRONT-MUD / APHP 200005
- Conditions
- Idiopathic Aplastic Anemia, Severe Aplastic Anemia, Moderate Aplastic Anemia Requiring Transfusions
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jun 2022 (estimated)
- Primary completion
- Aug 2025 (estimated)
- Study completion
- Jun 2027 (estimated)
- First posted
- 15 Jun 2022 (actual)
- 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.
Pediatric patients with idiopathic aplastic anemia (AA) respond better than adults to immunosuppressive therapy (IST) but the long-term risks of relapse, ciclosporine dependence, and clonal evolution are high. UK investigators reported a 5-year estimated failure-free survival (FFS) after IST of 13.3%. In contrast, in 44 successive children who received a matched unrelated donor (MUD), hematopoietic stem cell transplantation (HSCT), there was an excellent estimated 5-year FFS of 95%. Forty of these children had previously failed IST. Because of those excellent results, up-front fully matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) became an attractive first-line option. In 2005 to 2014, a UK cohort of 29 children with idiopathic AA thus received MUD HSCTs as first-line therapy (they did not receive IST prior to HSCT). Results were excellent, with low Graft versus Host Disease rates and only 1 death (idiopathic pneumonia). This cohort was then compared with historical matched controls, transplanted or not. Outcomes for the up-front unrelated cohort HSCT were similar to Matched Related Donor HSCT and superior to IST and unrelated HSCT post-IST failure. Since then, many investigators are offering up-front MUD HSCT in pediatric patients worldwide. However, those results should be treated with extreme caution: 1) the design is retrospective; 2) the excellent up-front MUD HSCT may arise from the use of alemtuzumab in the conditioning regimen (alemtuzumab is not easily available worldwide) and 3) there was no formal quality-of-life assessment. Moreover, this strategy is highly dependent on donor identification (Caucasian patients have the highest likelihood of having a MUD) and donor not eventually receive HSCT because of the risk of infections/complications caused by unexpected donor delays or cancellation. Prospective trials are thus urgently needed to address the feasibility of such procedure, in term of timing (delay to offer MUD HSCT) and conditioning regimen (nothing is known of the use of other regimens, non alemtuzumab-based, in this setting).
The main objective of this Two-Stage Phase 2 multicenter study is to realize up-front HSCT within 2 months once a MUD has been identified.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| HSCT arm group | Experimental | Other: HSCT Arm group1. Conditioning regimen 2. Stem cell source Only Bone Marrow With a minimal target dose of 4x108 nucleated cells/kg recipient ideal body weight. If the graft is less rich than the minimum target dose, it can be administered at the discretion to the physician. 3. GVHD Prophylaxis 4. Prevention of EBV reactivation : Rituximab 150mg/m2 IV at Day+5 post HSCT. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- age<18years old
- Pediatric patients aged less than 18 years with idiopathic aplastic anemia and an indication for treatment (severe aplastic anemia or moderate aplastic anemia requiring transfusions)
- With a good probability to have a HLA-10/10 matched unrelated donor available (the patient needs to have at least 3 MUD identified within the book BMDW (Bone Marrow Donors Worldwide) or using the easy match software to be included)
- With usual criteria for allo-SCT:
- Lansky >70% for those below 16 years and Karnofsky > 70% for those above 16 years
Key exclusion criteria (12 listed)
- With a matched related donor available
- With uncontrolled infection
- With seropositivity for HIV or HTLV-1 or active hepatitis B or C defined by a positive PCR HBV or HCV and associated hepatic cytolysis
- Renal failure with creatinine clearance below 70% of higher normal values for age
- Pregnant (βHCG positive) or breast-feeding
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 |
|---|---|---|
| HSCT Arm groupConditioning regimen Stem cell source Only Bone Marrow With a minimal target dose of 4x108 nucleated cells/kg recipient ideal body weight. If the graft is less rich than the minimum target dose, it can be administered at the discretion to the physician. GVHD Prophylaxis Prevention of EBV reactivation : Rituximab 150mg/m2 IV at Day+5 post HSCT. | Other | HSCT arm group |
Primary outcome
Proportion of patients with upfront matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) effectively performed
Time frame: within 2 months (60 days) after identification of a MUD
Proportion of patients with upfront matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) effectively performed in the first two months after unrelated donor search.
47 secondary outcomes
Graft failure incidence
Time frame: up to 24 months
Neutrophils engraftment
Time frame: at day 100
Platelets engraftment
Time frame: at day 100
Absolute number of neutrophils
Time frame: at 1 month
Absolute number of neutrophils
Time frame: at 2 months
Absolute number of neutrophils
Time frame: at 3 months
Absolute number of neutrophils
Time frame: at 6 months
Absolute number of neutrophils
Time frame: at 12 months
Absolute number of neutrophils
Time frame: at day of last platelet and red blood cell transfusions (assessed up to 24 months)
Absolute numbers of platelets
Time frame: at 1 month
Absolute numbers of platelets
Time frame: at 2 months
Absolute numbers of platelets
Time frame: at 3 months
Absolute numbers of platelets
Time frame: at 6 months
Absolute numbers of platelets
Time frame: at 12 months
Absolute numbers of platelets
Time frame: up to 24 months
Acute GvHD incidence
Time frame: at month 3
Chronic GvHD incidence
Time frame: at 24 months
Relapse incidence
Time frame: at 12 months
Relapse incidence
Time frame: at 24 months
Progression free survival
Time frame: at 12 months
Progression free survival
Time frame: at 24 months
Incidence of CMV infection
Time frame: at 12 months
Incidence of EBV infection
Time frame: at 12 months
Incidence of severe infections
Time frame: at 3 months
Incidence of severe infections
Time frame: at 6 months
Incidence of severe infections
Time frame: at 12 months
Incidence of severe infections
Time frame: at 24 months
Non-relapse mortality
Time frame: at 24 months
Overall survival
Time frame: at 24 months
Quality of life questionnaires PedsQL
Time frame: at inclusion
Quality of life questionnaires PedsQL
Time frame: at 1 month
Quality of life questionnaires PedsQL
Time frame: at 3 months
Quality of life questionnaires PedsQL
Time frame: at 6 months
Quality of life questionnaires PedsQL
Time frame: at 12 months
Quality of life questionnaires PedsQL
Time frame: at 24 months
Proportion of patients with a donor chimerism of 90% or more
Time frame: at 1 month
Proportion of patients with a donor chimerism of 90% or more
Time frame: at 3 months
Proportion of patients with a donor chimerism of 90% or more
Time frame: at 6 months
Proportion of patients with a donor chimerism of 90% or more
Time frame: at 12 months
Immune reconstitution
Time frame: at 3 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jun 2022.
- Individual participant dataSharing planned: Undecided
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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.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing HSCT Arm group in people with Idiopathic Aplastic Anemia and Severe Aplastic Anemia, run by Assistance Publique - Hôpitaux de Paris.
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 14 inclusion and 12 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: opening soon, as of the sponsor's last update on 15 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jean-Hugues Pr DALLES (+33140035388, jean-hugues.dalle@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Proportion of patients with upfront matched unrelated donor (MUD) hematopoietic stem cell transplantation (HSCT) effectively performed (time frame: within 2 months (60 days) after identification of a MUD). 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 15 Jun 2022.