Isatuximab for Improving Platelet Transfusion Effectiveness in Patients with Hematologic Malignancies

Inclusion Criteria

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, age >= 18 years
• Diagnosis of immune mediated platelet transfusion refractoriness secondary to class I anti-HLA antibodies: * Lack of adequate post-transfusion platelet corrected count increment (CCI), defined by CCI < 7500/uL at 10-60 minutes post transfusion, after at least 2 consecutive general inventory apheresis platelet (AP) unit transfusions * Calculated percent panel-reactive antibodies (%PRA) > 80%
• Serum creatinine =< 1.5 x upper limit of normal (ULN)
• Bilirubin =< 1.5 x ULN (except in patients with Gilbert's disease, where bilirubin to 4 x ULN is allowed)
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =< 2.5 x ULN
• Alkaline phosphatase =< 2.5 x ULN
• For females and males of reproductive potential: agreement to use adequate contraception
• Agreement to adhere to lifestyle considerations throughout study duration

Exclusion Criteria

• Immune-mediated platelet refractoriness other than anti-HLA antibody-mediated
• Non-immune-mediated platelet refractoriness (e.g. splenomegaly or disseminated intravascular coagulation)
• Diagnosis of thrombocytopenia induced by other drugs, such as vancomycin, heparin, or amphotericin
• Diagnosis of thrombotic thrombocytopenic purpura or idiopathic immune thrombocytopenia
• Active bleeding
• Greater than grade 2 active graft versus host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (HSCT)
• Bi-directional ABO mismatched allogeneic stem cell transplantation
• Prior administration of daratumumab, isatuximab or any other anti-CD38 antibodies
• Known uncontrolled human immunodeficiency virus (HIV) disease and/or active hepatitis A, B, or C infection * Uncontrolled or active hepatitis B virus (HBV) infection: Patients with positive hepatitis B virus surface antigen (HBsAg) and/or HBV deoxyribonucleic acid (DNA) ** Patient can be eligible if anti-hepatitis B virus core (HBc) immunoglobulin G (IgG) positive (with or without positive anti-hepatitis B virus surface antigen [HBs]) but HBsAg and HBV DNA are negative *** If anti-HBV therapy in relation with prior infection was started before initiation of investigational medicinal product (IMP), the anti-HBV therapy and monitoring should continue throughout the study treatment period ** Patients with negative HBsAg and positive HBV DNA observed during screening period will be evaluated by a specialist for start of anti-viral treatment: study treatment could be proposed if HBV DNA becomes negative and all the other study criteria are still met * Active hepatitis C virus (HCV) infection: positive HCV ribonucleic acid (RNA) and negative anti-HCV ** Patients with antiviral therapy for HCV started before initiation of IMP and positive HCV antibodies are eligible. The antiviral therapy for HCV should continue throughout the treatment period until seroconversion ** Patients with positive anti-HCV and undetectable HCV RNA without antiviral therapy for HCV are eligible * Uncontrolled HIV disease: HIV positive with HIV viral load > 20 IU/mL and CD4 count < 200 cells/mm^3 ** Patients with HIV positive disease on anti-retroviral therapy (ART) with HIV viral load < 20 IU/mL and CD4 count > 200 cells/mm^3 are allowed to be enrolled on the study.
• Active systemic infection and severe infections requiring treatment with a parenteral administration of antimicrobials * Controlled systemic infections on antimicrobial therapy that are stable at the time of screening are not an exclusion criterion
• Hypersensitivity 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 intervention that are not amenable to premedication with steroids and H2 blockers or would prohibit further treatment with these agents
• Received any investigational drug within 14 days or 5 half-lives of the investigational drug prior to initiation of study intervention, whichever is longer. In case of very aggressive disease (i.e acute leukemia) delay could be shortened after agreement between sponsor and investigator, in absence of residual toxicities from previous therapy
• Pregnancy or lactation
• Any clinically significant, uncontrolled medical conditions that, in the Investigator's opinion, would expose the patient to excessive risk or may interfere with compliance or interpretation of the study results
• Current receipt of, or expectation to require anti-CD20 therapy, proteasome inhibitors, intravenous immune globulin ("IVIG"), and plasma exchange therapy during the study