Patients with beta-thalassemia major who are eligible for a haploidentical HSCT MedDRA version: 19.0 Level: LLT Classification code 10054661 Term: Thalassemia major System Organ Class: 100000004850
Conditions
Interventions
Product Name: ATIR201
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: -
CAS Number: -
Current Sponsor code: -
Sponsors
Kiadis Pharma Netherlands B.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Patient Inclusion Criteria: • Confirmed diagnosis of beta-thalassemia major: - Hypertransfusion program with eight or more red blood cell (RBC) transfusions a year and a confirmed annual transfusion of = 100 ml/kg/year. - Genotype consistent with clinical diagnosis of beta-thalassemia major (including hemoglobin E-beta-thalassemia genotype) - Iron chelation therapy initiated, or not yet initiated but at risk of transfusional iron overload • Lansky / Karnofsky performance score > 70% • Eligible for haploidentical stem cell transplantation according to the investigator taking into account the feasibility of transplanting patients with pre-existing antibodies (e.g. anti-A, anti-B, and/or other anti-donor red cell antibodies or known presence of HLA antibodies against the non-shared donor haplotype) • Male or female, age = 2 years and = 25 years Donor Inclusion Criteria: • Haploidentical family donor with at least 4 out of 8 or 5 out of 10 matches at the HLA- A, -B , -C, -DR, and/or DQ loci as determined by high resolution typing • Male or female, age = 16 and = 75 years (If applicable, local legal requirements for donors under the age of 18 will be followed) • Eligible for donations of human blood and blood components according to local requirements and regulations • Fit to receive granulocyte colony-stimulating factor (G-CSF) and to give peripheral blood stem cells (blood counts and blood pressure within standards) • Eligible for donation according to the transplantation center Are the trial subjects under 18? yes Number of subjects for this age range: 7 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 3 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: Exclusion Criteria Patient: • Availability of a fully matched related or unrelated donor following a donor search, which might have been initiated before screening. • Patient assigned to Pesaro risk class 3 • Symptomatic cardiac failure: left ventricular ejection fraction at rest 5 times the upper limit of normal range (ULN) for age of AST or > 2.5 times the ULN for age of total serum bilirubin • Renal function (creatinine clearance or GFR) < 50% of the lower limit of normal (LLN) for age • Symptomatic pulmonary failure: DLCO, FEV1, or FEC (diffusion capacity) < 50% of predicted (corrected for hemoglobin); if unable to perform a pulmonary function test, oxygen saturation < 85% on room air • Positive pregnancy test (females of childbearing age only) • Positive test for HIV-1 or HIV-2 • Active viral, bacterial, fungal, or parasitic infection, including hepatitis B, hepatitis C • Prior HSCT for beta-thalassemia major • Known allergy to any of the components of ATIR201 (e.g., dimethyl sulfoxide) • Any other condition which, in the opinion of the investigator, makes the patient ineligible for the study Donor Exclusion Criteria: • Positive pregnancy test or nursing (females of childbearing age only) • Positive viral test for HIV-1, HIV-2, HBV, HCV, or Treponema pallidum • Hemoglobin S = 50%, or presence of beta-thalassemia intermedia • History of congestive heart failure, unstable angina, or history of stroke
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of the study is to evaluate the safety and feasibility of ATIR201 in patients with beta-thalassemia major who received a T-cell depleted haploidentical hematopoietic stem cell transplantation (HSCT). Safety and tolerability will be primarily evaluated by the occurrence of acute graft-versus- host disease (GVHD) grade III/IV within 180 days post HSCT. Efficacy will be primarily evaluated by transfusion-free survival (TFS), occurrence of severe infections, and time to T-cell reconstitution, taking into account hematologic and sustained engraftment. ;Secondary Objective: Not applicable;Primary end point(s): Incidence of acute graft versus host disease (GvHD) grade III/IV within 180 days post HSCT.;Timepoint(s) of evaluation of this end point: 180 days post HSCT | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary safety endpoints: • Occurrence of acute and chronic GVHD (all grades/severities) • Occurrence of graft rejection • Occurrence of prolonged donor red cell aplasia • Donor chimerism Secondary efficacy endpoints: • Transfusion-free survival (TFS) • Occurrence of severe (NCI grade 3-5) infections • Time to T-cell reconstitution, defined as the time to CD3+ > 0.2×10E9/l in peripheral blood (at two consecutive measurements; time to first measurement) • Overall survival (OS), defined as the time from HSCT until death from any cause • Transplant-related mortality (TRM), defined as death due to causes other than disease recurrence ;Timepoint(s) of evaluation of this end point: Up to 12 months post HSCT | — |
Countries
Germany, United Kingdom
Contacts
Public ContactDirector Clinical Operations
Kiadis Pharma Netherlands B.V.
Outcome results
None listed