Pure cell red aplasia by major ABO mismatch after allogeneic hematopoietic stem cell transplantation MedDRA version: 20.0 Level: PT Classification code 10002965 Term: Aplasia pure red cell System Organ Class: 10005329 - Blood and lymphatic system disorders
Conditions
Interventions
Trade Name: Sarclisa
Product Name: isatuximab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Isatuximab
Other descriptive name: Anti CD38 antibody
Concentration unit:
Sponsors
ASSISTANCE PUBLIQUE -HOPITAUX DE PARIS
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Aged 15 years or older - Having receiving an allogeneic hematopoietic stem cell transplantation in condition of major ABO mismatch - PCRA defined by persistent red blood cell transfusion dependence at day 60 post-transplant with reticulocytes count under 10 G/L despite full donor chimerism and a good leucocytes (>1 G/L) and platelet (>50G/L) recovery - No relapse or progression of underlying disease - Contraception methods must be prescribed during all the duration of the research and using effective contraceptive methods during treatment for women of childbearing age (continue abstinence from heterosexual intercourse is accepted) and for man during the study treatment period and for at least 5 months after the last dose of study treatment and refrain from donating sperm during this period - With health insurance coverage - Having signed a written informed consent (2 parents for patients aged less than 18) Are the trial subjects under 18? yes Number of subjects for this age range: 6 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 64 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: - Aged < 15 years - Relapse of underlying disease - Leucocyte chimerism < 95% - PRCA related to Parvovirus B19 infection (positive blood PCR) - Known to be HIV+ or to have hepatitis A, B, or C active infection - Active tuberculosis - Pregnancy (ßHCG positive) or breast-feeding. - Patient receiving recombinant human erythropoietin. - Patient receiving proteasome inhibitor (Bortezomib for example). - Patient receiving thrombopoietin receptor agonists (ARTPO). - Patient receiving plasma or plasmapheresis exchanges after transplant. - Planned to receive any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer. - Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose excessive risk to the patient or may interfere with compliance or interpretation of the study results. - Hypersensitivity to the active substance or history of intolerance to steroids, mannitol, pregelatinized starch, sodium stearyl fumarate, histidine (as base and hydrochloride salt), arginine, hydrochloride, poloxamer 188, sucrose or any of the other components of study therapy that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents. - Who have any debilitating medical or psychiatric illness - Under tutorship or curatorship - Who not understand informed consent for an optimal treatment and follow-up
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Efficacy of the treatment of PRCA by isatuximab after allogeneic hematopoietic stem cell transplant compared to supportive care only control group (reduction in PRCA resolution time in days);Secondary Objective: 1/ To evaluate the two arms in term of clinical and biological outcomes: -Reduction of red blood cells transfusion needs with Isatuximab -Evolution of iron overload -Adverse events related to Isatuximab in the context of allogeneic SCT (CTC-AE grade = 2 in each group after M6 post-transplant) -Quality of life: functional repercussions of chronic anemia, iterative transfusions and iron overload at d29, 3, 6, 9 months after randomization 2/ To identify prognostic factors of spontaneous resolution of PRCA by major ABO mismatch between D60 and M6 (type of donor, cell stem cell and conditioning regimen, occurrence of acute or chronic graft versus host disease, discontinuation of immunosuppression) 3/ To evaluate the interest of follow-up of group hemagglutinins 4/ To compare both arms in term of-cost effectiveness (cost of isatuximab treatment, hospitalizations, transfusion support and chelation treatments) ;Primary end point(s): Time to obtention of transfusion independence for patients with PRCA: time interval between randomization (corresponding to the M6 post-transplant) and resolution of PRCA (date of resolution of reticulocytopenia) treated or not by the anti-CD 38 monoclonal antibody isatuximab;Timepoint(s) of evaluation of this end point: M6 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): -Number of red blood cell transfusions after randomization -Ferritin levels at M6, M9 and M15 post-transplant -Adverse events (CTC-AE grade = 2) after randomization -Quality of life questionnaire (EORTC QLQ-C30- v3) at D60, D100, M6, M9, M12, M15 post-transplant -Factors associated with spontaneous resolution of PRCA between D60 and M6 post-transplant - Antibody level (anti A and/or anti B titers) at D60, D100, M6 post-transplant then at each visit d15, d29, d45, and M3, M6, M9 post randomization, - Number of days of hospitalization, transfusions support and chelation treatments ;Timepoint(s) of evaluation of this end point: -Number of red blood cell transfusions after randomization -Ferritin levels at M6, M9 and M15 post-transplant -Adverse events (CTC-AE grade = 2) after randomization -Quality of life questionnaire (EORTC QLQ-C30- v3) at D60, D100, M6, M9, M12, M15 post-transplant -Factors associated with spontaneous resolution of PRCA between D60 and M6 post-transplant - Antibody level (anti A and/or anti B titers) at D60, D100, M6 post-transplant then at each visit d15, d29, d45, and M3, M6, M9 post randomization, - Number of days of hospitalization, transfusions support and chelation treatments | — |
Countries
France
Contacts
Public ContactDRCI Hôpital Saint Louis
ASSISTANCE PUBLIQUE - HOPITAUX DE PARIS
Outcome results
None listed