A Pilot Trial Using Isatuximab to Overcome Platelet Transfusion Refractoriness in Human Leukocyte Antigen Allo-Immunized Patients (SuppCare 001)

Inclusion Criteria:

1. Provision of signed and dated informed consent form

2. Stated willingness to comply with all study procedures and availability for theduration of the study

3. Male or female, age ≥ 18 years

4. Diagnosis of immune mediated platelet transfusion refractoriness secondary to classI anti-HLA antibodies according to institutional practice, including calculatedpercent panel-reactive antibodies (%PRA) > 80%

5. Adequate Organ Function:

• serum creatinine <= 1.5 x upper limit of normal

• bilirubin <= 1.5 x upper limit of normal (exceptions for Gilbert's disease)

• AST and ALT <= 2.5 x upper limit of normal

• Alkaline phosphatase <= 2.5 x upper limit of normal

6. For females and males of reproductive potential: agreement to use adequatecontraception (see section 5.3)

7. Agreement to adhere to Lifestyle Considerations (see Section 5.3) throughout studyduration

Exclusion Criteria:

1. Immune-mediated platelet refractoriness other than anti-HLA antibody-mediated

2. Non-immune-mediated platelet refractoriness (e.g. splenomegaly or disseminatedintravascular coagulation)

3. Diagnosis of thrombocytopenia induced by other drugs, such as vancomycin, heparin,or amphotericin

4. Diagnosis of thrombotic thrombocytopenic purpura or idiopathic immunethrombocytopenia

5. Active bleeding

6. Greater than Grade 2 active graft versus host disease (GVHD) following allogeneicHSCT

7. Bi-directional ABO mismatched allogeneic stem cell transplantation

8. Prior administration of daratumumab, isatuximab or any other anti-CD38 antibodies

9. Known uncontrolled HIV disease and/or active Hepatitis A, B, or C infection

10. Active systemic infection and severe infections requiring treatment with aparenteral administration of antimicrobials.

• Controlled systemic infections on antimicrobial therapy that are stable at thetime of screening are not an exclusion criterion.

11. Hypersensitivity or history of intolerance to steroids, mannitol, pregelatinizedstarch, sodium stearyl fumarate, histidine (as base and hydrochloride salt),arginine hydrochloride, poloxamer 188, sucrose or any of the other components ofstudy intervention that are not amenable to premedication with steroids and H2blockers or would prohibit further treatment with these agents.

12. Received any investigational drug within 14 days or 5 half-lives of theinvestigational drug prior to initiation of study intervention, whichever is longer.In case of very aggressive disease (i.e acute leukemia) delay could be shortenedafter agreement between sponsor and investigator, in absence of residual toxicitiesfrom previous therapy

13. Pregnancy or lactation

14. Any clinically significant, uncontrolled medical conditions that, in theInvestigator's opinion, would expose the patient to excessive risk or may interferewith compliance or interpretation of the study results.

15. Current receipt of, or expectation to require anti-CD20 therapy, proteasomeinhibitors, intravenous immune globulin ("IVIG"), and plasma exchange therapy duringthe study