E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Pure cell red aplasia by major ABO mismatch after allogeneic hematopoietic stem cell transplantation |
Erythroblastopénies par incompatibilité ABO majeure après allogreffe de cellules souches hématopoïétiques. |
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E.1.1.1 | Medical condition in easily understood language |
Pure cell red aplasia by major ABO mismatch after allogeneic hematopoietic stem cell transplantation |
Erythroblastopénies par incompatibilité ABO majeure après allogreffe de cellules souches hématopoïétiques. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10002965 |
E.1.2 | Term | Aplasia pure red cell |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
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) |
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E.2.2 | Secondary objectives of the trial |
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)
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal 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)
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E.4 | Principal 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 (βHCG 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
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E.5 End points |
E.5.1 | 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 |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | 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
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E.5.2.1 | 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
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
no experimental treatment |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 18 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | 49 |
E.8.9.1 | In the Member State concerned days | |