An official website of the United States government
Government Funding Lapse Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted.
The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit cc.nih.gov.
Updates regarding government operating status and resumption of normal operations can be found at opm.gov.
IVIG for Infection Prevention after CAR-T-Cell Therapy
Trial Status: active
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.
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
Additional locations may be listed on ClinicalTrials.gov for NCT05952804.
I. To compare the incidence rate of serious bacterial infections during the first six months after CD19-CARTx in patients randomized to receive monthly immunoglobulin replacement therapy (IGRT) versus placebo in a modified intention-to-treat (mITT) analysis.
SECONDARY OBJECTIVES:
I. To compare the incidence rate of serious bacterial infections in the intention-to-treat (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.
II. To characterize levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG and compare levels between study arms.
III. To test for associations of levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG with infections.
IV. To compare health-resource utilization (HRU) between study arms.
V. To compare the incidence and severity of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) between study arms.
VI. To compare CAR T-cell expansion between study arms.
VII. To compare CAR T-cell persistence between study arms.
VIII. To compare CAR T-cell phenotype and function at day 14 after infusion between study arms.
IX. To compare all immune cell subset phenotypes and functional makers at end of study between study arms.
X. To compare IgA and IgM at end of study between study arms.
XI. To compare health related quality of life (HRQOL) between study arms.
OUTLINE: Patients are randomized to 1 of 2 arms.
ARM I: Patients receive IGRT with intravenous immune globulin (IVIG) within 14 days prior to CD19 CAR-T treatment. Patients then undergo CD19 CAR-T-cell infusion. Patients receive IVIG monthly, starting 28 days after CD19 CAR-T therapy for up to 4 months in the absence of unacceptable toxicity, relapse of the underlying disease, or subsequent hematopoietic cell transplant. Patients also undergo blood sample collection throughout the study.
ARM II: Patients receive placebo with normal saline IV within 14 days prior to CD19 CAR-T treatment. Patients then undergo CD19 CAR-T-cell infusion. Patients receive normal saline monthly, starting 28 days after CD19 CAR-T therapy for up to 4 months in the absence of unacceptable toxicity, relapse of the underlying disease, or subsequent hematopoietic cell transplant. Patients also undergo blood sample collection throughout the study.
After completion of study treatment, patients are followed up monthly through up to 6 months after CD19 CAR-T-cell infusion.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationFred Hutch/University of Washington/Seattle Children's Cancer Consortium
