Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT05419843
Other study ID # APHP 200005
Secondary ID
Status Not yet recruiting
Phase Phase 2
First received
Last updated
Start date June 2022
Est. completion date June 2027

Study information

Verified date May 2022
Source Assistance Publique - Hôpitaux de Paris
Contact Jean-Hugues Pr DALLES
Phone +33140035388
Email jean-hugues.dalle@aphp.fr
Is FDA regulated No
Health authority
Study type Interventional

Clinical 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%. 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.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 25
Est. completion date June 2027
Est. primary completion date August 2025
Accepts healthy volunteers No
Gender All
Age group N/A to 18 Years
Eligibility Inclusion Criteria: - 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 - 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 Exclusion Criteria: 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 (ßHCG positive) or breast-feeding - 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

Study Design


Related Conditions & MeSH terms


Intervention

Other:
HSCT Arm group
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.

Locations

Country Name City State
n/a

Sponsors (1)

Lead Sponsor Collaborator
Assistance Publique - Hôpitaux de Paris

Outcome

Type Measure Description Time frame Safety issue
Primary 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. within 2 months (60 days) after identification of a MUD
Secondary Graft failure incidence up to 24 months
Secondary Neutrophils engraftment Neutrophils engraftment will be defined as first day of 3 consecutive days with neutrophils >0.5 G/L at day 100
Secondary Platelets engraftment Platelets engraftment will be defined as first day of 7 consecutive days with platelets >20 G/L at day 100
Secondary Absolute number of neutrophils at 1 month
Secondary Absolute number of neutrophils at 2 months
Secondary Absolute number of neutrophils at 3 months
Secondary Absolute number of neutrophils at 6 months
Secondary Absolute number of neutrophils at 12 months
Secondary Absolute number of neutrophils at day of last platelet and red blood cell transfusions (assessed up to 24 months)
Secondary Absolute numbers of platelets at 1 month
Secondary Absolute numbers of platelets at 2 months
Secondary Absolute numbers of platelets at 3 months
Secondary Absolute numbers of platelets at 6 months
Secondary Absolute numbers of platelets at 12 months
Secondary Absolute numbers of platelets up to 24 months
Secondary Acute GvHD incidence at month 3
Secondary Chronic GvHD incidence at 24 months
Secondary Relapse incidence at 12 months
Secondary Relapse incidence at 24 months
Secondary Progression free survival at 12 months
Secondary Progression free survival at 24 months
Secondary Incidence of CMV infection at 12 months
Secondary Incidence of EBV infection at 12 months
Secondary Incidence of severe infections Severe infections will be defined as CTACE grade 3-4 at 3 months
Secondary Incidence of severe infections Severe infections will be defined as CTACE grade 3-4 at 6 months
Secondary Incidence of severe infections Severe infections will be defined as CTACE grade 3-4 at 12 months
Secondary Incidence of severe infections Severe infections will be defined as CTACE grade 3-4 at 24 months
Secondary Non-relapse mortality at 24 months
Secondary Overall survival at 24 months
Secondary 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. at inclusion
Secondary 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. at 1 month
Secondary 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. at 3 months
Secondary 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. at 6 months
Secondary 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. at 12 months
Secondary 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. at 24 months
Secondary Proportion of patients with a donor chimerism of 90% or more at 1 month
Secondary Proportion of patients with a donor chimerism of 90% or more at 3 months
Secondary Proportion of patients with a donor chimerism of 90% or more at 6 months
Secondary Proportion of patients with a donor chimerism of 90% or more at 12 months
Secondary 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 at 3 months
Secondary 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 at 6 months
Secondary 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. at 12 months
Secondary 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. at 24 months
Secondary Ferritin levels at 3 months
Secondary Ferritin levels at 6 months
Secondary Ferritin levels at 12 months
Secondary Ferritin levels at 24 months
See also
  Status Clinical Trial Phase
Recruiting NCT02828592 - Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia Phase 2
Completed NCT02833805 - NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia Phase 2
Terminated NCT01319851 - Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation N/A
Completed NCT00004143 - Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes Phase 2
Recruiting NCT05012111 - Natural History of Acquired and Inherited Bone Marrow Failure Syndromes
Recruiting NCT03836690 - Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation Phase 1
Recruiting NCT06039436 - Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired SAA Receiving sUCBT
Enrolling by invitation NCT05049668 - RACE 2: a Long Term Follow-up of Patients Participating in the RACE Trial
Recruiting NCT01472055 - Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation Phase 2
Recruiting NCT01351545 - A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs)
Completed NCT01703169 - Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia Phase 2
Withdrawn NCT01129323 - Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia N/A
Completed NCT00516152 - Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT Phase 2
Recruiting NCT06069180 - The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA Phase 4
Recruiting NCT03579875 - Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders Phase 2
Recruiting NCT05720234 - Avatrombopag Combined With IST as First-line Treatment for SAA Phase 2
Recruiting NCT04304820 - Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA) Phase 2
Terminated NCT00358657 - Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus, and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders Phase 2
Completed NCT02998645 - Eltrombopag Combined With Cyclosporine as First Line Therapy in Patients With Severe Acquired Aplastic Anemia Phase 2
Active, not recruiting NCT03825744 - Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia Phase 3