Clinical Trial 23184

• Overview

  Study Title:

  Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy (CARIsMA)

  Summary:

  This phase II trial compares the effects of immunoglobulin replacement therapy with a placebo for preventing infectious complications in patients receiving CD19 chimeric antigen receptor (CAR)-T cell therapy. Hypogammaglobulinemia is a common complication in patients who receive CD19 CAR-T cell therapy. This is a condition in which the level of immunoglobulins (antibodies) in the blood is low and the risk of infection is high. Immunoglobulin replacement therapy works by replacing the body's immunoglobulin G (IgG) antibodies with donor blood product derived IgG antibodies that may help prevent infection. IgG antibodies are often depleted as a result of CAR-T therapy. Giving immunoglobulin replacement therapy may prevent infectious complications in patients receiving CD19 CAR-T cell therapy.

  Objective:

  Primary: To compare the incidence rate of serious bacterial infections during the first six months after CD19-CARTx in patients randomized to receive monthly antibody infusions versus placebo in a modified intention-to-treat (mITT) analysis. Secondary: 1. To compare the incidence rate of serious bacterial infections in the ITT and per-protocol populations, and of any serious infection or any infection after CD19-CARTx between study arms in the mITT, ITT, and per-protocol (complete adherence to IGRT assignment) populations. 2. To characterize levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG and compare levels between study arms. 3. To test for associations of levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG with infections. 4. To compare HRU between study arms. 5. To compare the incidence and severity of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) between study arms. 6. To compare CAR T-cell expansion between study arms. 7. To compare CAR T-cell persistence between study arms. 8. To compare CAR T-cell phenotype and function at day 14 after infusion between study arms. 9. To compare all immune cell subset phenotypes and functional makers at the end of the study between study arms. 10. To compare IgA and IgM at end of study between study arms. 11. To compare health-related quality of life (HRQOL) between study arms.

• Treatments

  Therapies:

  Cell Therapy; Immunotherapy

  Medications:

  Placebo ()

• Inclusion Criteria

  Key Inclusion Criteria:
  • Capable of understanding the investigational nature, potential risks and benefits of the study, and able to provide valid informed consent
  • For patients with medical incapacity or impaired consciousness such that they are not able to give fully informed voluntary consent, the subjects' legal representative must sign an institutional review board (IRB) approved informed consent document prior to the initiation of any screening or study-specific procedures
  • Participants must be 18 years of age or older
  • Participants will receive an Food and Drug Administration (FDA)-approved CD19-CAR T-cell product for the treatment of hematologic malignancies. Patients receiving an FDA-approved product are eligible even if the product is being administered as part of a clinical trial or expanded access program (e.g., product is 'out of specification'; concomitant anti-tumor treatment such as acalabrutinib)
  • Serum total IgG > SUBSEQUENT INFUSIONS: Received an FDA-approved CD19-CAR T-cell product for the treatment of hematologic malignancies

• Exclusion Criteria

  Key Exclusion Criteria:
  • Primary congenital selective IgA deficiency
  • Prior serious adverse event/s related to intravenous immune globulin (IVIG) administration
  • Known serious allergy to any component of IVIG
  • Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study or interfere with the patient's ability to participate for the full duration of the study or would put the patient at undue risk as judged by the investigator, such that it is not in the best interest of the patient to participate in this study
  • SUBSEQUENT INFUSIONS: Ongoing symptoms of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) meeting criteria for grade 3 or higher
  • SUBSEQUENT INFUSIONS: Primary congenital selective IgA deficiency
  • SUBSEQUENT INFUSIONS: Has a history or current evidence of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study or interfere with the patient's ability to participate for the full duration of the study or would put the patient at undue risk as judged by the Investigator, such that it is not in the best interest of the patient to participate in this study
  • SUBSEQUENT INFUSIONS: Receipt of additional therapy for persistence or relapse of the patient's primary malignancy
  • SUBSEQUENT INFUSIONS: Receipt of bone marrow transplant (allogeneic or autologous)
  • SUBSEQUENT INFUSIONS: Any serious adverse event (SAE), clinically significant adverse event (AE), severe laboratory abnormality, intercurrent illness, or other medical condition that indicates to the Investigator that continued participation is not in the best interest of the participant

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