Using immunoglobulin therapy to prevent infections after CAR-T cell treatment

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

This study is testing if giving extra antibodies through immunoglobulin therapy can help prevent infections in patients receiving CAR-T cell treatment for blood cancers.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 150 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Fred Hutchinson Cancer Center (Academic / other)
• Drugs / interventions: acalabrutinib, CAR T, CAR-T, chimeric antigen receptor
• Locations: 7 sites (Duarte, California and 6 other locations)
• Trial ID: NCT05952804 on ClinicalTrials.gov

What this trial studies

This phase II trial investigates the effectiveness of immunoglobulin replacement therapy compared to a placebo in preventing infections in patients undergoing CD19 CAR-T cell therapy for hematologic malignancies. Patients are randomly assigned to receive either intravenous immune globulin (IVIG) or a placebo prior to and following their CAR-T cell infusion. The study aims to address hypogammaglobulinemia, a common complication that increases infection risk in these patients, by providing additional IgG antibodies. Participants will be monitored for up to six months post-treatment to assess the incidence of infectious complications.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older who are receiving FDA-approved CD19 CAR-T cell therapy and have low serum total IgG levels.

Not a fit: Patients who do not have low IgG levels or are not receiving CD19 CAR-T therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the risk of infections in patients receiving CAR-T cell therapy.

How similar studies have performed: Other studies have shown promise in using immunoglobulin therapy for infection prevention in similar patient populations, suggesting a potential for success in this approach.

Eligibility criteria

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 \< 600mg/dL within the prior three months
* SUBSEQUENT INFUSIONS: Received an FDA-approved CD19-CAR T-cell product for the treatment of hematologic malignancies

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

Where this trial is running

Duarte, California and 6 other locations

• City of Hope Cancer Center — Duarte, California, United States (Recruiting)
• University of Miami Miller School of Medicine-Sylvester Cancer Center — Miami, Florida, United States (Recruiting)
• Moffitt Cancer Center — Tampa, Florida, United States (Recruiting)
• Massachusetts General Hospital Cancer Center — Boston, Massachusetts, United States (Recruiting)
• Memorial Sloan Kettering Cancer Center — New York, New York, United States (Recruiting)
• Oregon Health and Science University (OHSU) Knight Cancer Institute — Portland, Oregon, United States (Recruiting)
• Fred Hutch/University of Washington Cancer Consortium — Seattle, Washington, United States (Recruiting)

Study contacts

• Principal investigator: Joshua Hill, MD — Fred Hutch/University of Washington Cancer Consortium
• Study coordinator: Joshua Hill, MD

Conditions Hematologic Malignancies