Randomized prospective trial evaluating the efficacy of the antiCD38 monoclonal antibody isatuximab in the treatment of PCRA by major ABO mismatch after allogeneic hematopoietic stem cell transplantation

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Hemic and Lymphatic Diseases [C15]

Trial duration

20 Feb 2023 → ongoing

Decision date (initial)

2024-08-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Ministry of Health

External identifiers

EU CT number

2024-514351-14-00

EudraCT number

2021-000932-70

ClinicalTrials.gov

NCT05559827

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

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 objectives 4

1. 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 - Overall survival and without relapse at M6, M9, M12 and M15 post-transplant
2. 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. 3/ To evaluate the interest of follow-up of group hemagglutinins
4. 4/ To compare both arms in term of-cost effectiveness (cost of isatuximab treatment, hospitalizations, transfusion support and chelation treatments)

Conditions and MedDRA coding

Pure cell red aplasia by major ABO mismatch after allogeneic hematopoietic stem cell transplantation

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. - Aged 15 years or older
2. - Having receiving an allogeneic hematopoietic stem cell transplantation in condition of major ABO mismatch
3. - 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
4. - No relapse or progression of underlying disease
5. - Contraception 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
6. - With health insurance coverage
7. - Having signed a written informed consent (2 parents for patients aged less than 18)

Exclusion criteria 16

1. - Aged < 15 years
2. - Relapse of underlying disease
3. - Leucocyte chimerism < 95%
4. - PRCA related to Parvovirus B19 infection (positive blood PCR)
5. Known to be HIV+ or to have hepatitis A, B, or C active infection
6. Active tuberculosis
7. Pregnancy (βHCG positive) or breast-feeding.
8. Patient receiving recombinant human erythropoietin.
9. Patient receiving proteasome inhibitor (Bortezomib for example).
10. Patient receiving thrombopoietin receptor agonists (ARTPO).
11. Patient receiving plasma or plasmapheresis exchanges after transplant.
12. - Planned to receive any investigational drug within 14 days or 5 half-lives of the investigational drug, whichever is longer.
13. 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.
14. - 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.
15. Who have any debilitating medical or psychiatric illness - Under tutorship or curatorship
16. Who not understand informed consent for an optimal treatment and follow-up

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 4

1. -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
2. Factors associated with spontaneous resolution of PRCA between D60 and M6 post-transplant
3. - 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,
4. - Number of days of hospitalization, transfusions support and chelation treatments

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Alienor XHAARD

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Alienor XHAARD

Locations

1 EU/EEA country · 20 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 8 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications