ISATUXIMAB for Pure red cell aplasia (post-allogeneic hematopoietic stem cell transplantation due to major ABO mismatch)

Inclusion criteria

• {"criterion_text":"-\tAged 15 years or older\n-\tHaving receiving an allogeneic hematopoietic stem cell transplantation in condition of major ABO mismatch\n-\tPCRA 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\n-\tNo relapse or progression of underlying disease\n-\tContraception methods must be prescribed during all the duration of the clinical trial 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\n-\tWith health insurance coverage\n-\tHaving signed a written informed consent (2 parents for patients aged less than 18)"}

Exclusion criteria

• {"criterion_text":"-\tAged < 15 years\n- Patient receiving thrombopoietin receptor agonists (ARTPO).\n- Patient receiving plasma or plasmapheresis exchanges after transplant.\n- Planned to receive any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.\n- 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.\n- 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.\n- Who have any debilitating medical or psychiatric illness - Under tutorship or curatorship\n- Who not understand informed consent for an optimal treatment and follow-up\n-\tRelapse of underlying disease\n-\tLeucocyte chimerism < 95%\n-\tPRCA related to Parvovirus B19 infection (positive blood PCR)\n-Known to be HIV+ or to have hepatitis A, B, or C active infection\n-Active tuberculosis\n-Pregnancy (βHCG positive) or breast-feeding.\n-Patient receiving recombinant human erythropoietin.\n-Patient receiving proteasome inhibitor (Bortezomib for example)."}

Primary endpoints

• {"endpoint_text":"-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","definition_or_measurement_approach":"Measured as the time interval (in days) between randomization (which corresponds to month 6 post-transplant) and the date of resolution of reticulocytopenia (i.e., achievement of transfusion independence) in patients treated with isatuximab versus control."}

Secondary endpoints

• {"endpoint_text":"-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","definition_or_measurement_approach":"Number of RBC transfusions: count of transfusion units after randomization; Ferritin levels measured at specified timepoints (M6, M9, M15 post-transplant); Adverse events graded by CTCAE with focus on grade ≥2 after randomization; QoL assessed using EORTC QLQ-C30 v3 at specified visits."}
• {"endpoint_text":"-Factors associated with spontaneous resolution of PRCA between D60 and M6 post-transplant","definition_or_measurement_approach":"Identification of prognostic factors (e.g., donor type, graft type, conditioning regimen, occurrence of acute/chronic GvHD, discontinuation of immunosuppression) associated with spontaneous resolution between day 60 and month 6 post-transplant."}
• {"endpoint_text":"- 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,","definition_or_measurement_approach":"Measurement of anti-A and/or anti-B antibody titers at listed timepoints to follow iso-hemagglutinin levels."}
• {"endpoint_text":"- Number of days of hospitalization, transfusions support and chelation treatments","definition_or_measurement_approach":"Counts/durations of hospitalisation days, number of transfusion support days/units, and use/duration of chelation treatments collected after randomization."}

France

Earliest CTIS Part Ii Submission Date

21-06-2024

Latest Decision Or Authorization Date

25-02-2026

Processing Time Days

614

Number Of Sites

20

Number Of Participants

90

Primary sponsor

Full Name

Assistance Publique Hopitaux De Paris

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

France