IVIG for Infection Prevention After CAR-T-Cell Therapy

Official title

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

Overview

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.

Detailed description

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive immunoglobulin replacement therapy (IGRT) with intravenous immune globulin (IVIG) within 14 days prior to CD19 CAR-T-cell infusion. Patients then undergo CD19 CAR-T therapy. 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. Doses 3, 4, and 5 are highly encouraged but not required. 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. Doses 3, 4, and 5 are highly encouraged but not required. 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.

Interventions

• Biological Immune Globulin Infusion (Human), 10% Solution
  Given IV
• Biological Anti-CD19 CAR T Cells Preparation
  Given CAR-T treatment
• Other Saline
  Given IV
• Procedure Biospecimen Collection
  Undergo blood sample collection
• Other Survey Administration
  Ancillary studies
• Other Electronic Health Record Review
  Ancillary studies

Primary outcome measures

• Incidence rate of serious bacterial infections in the modified intention-to-treat (mITT) population [Time frame: From randomization through day 168 post chimeric antigen receptor (CAR) T-cell treatment (CARTx)]

Secondary outcome measures (11)

• Incidence rate of serious bacterial infections in ITT and per-protocol populations and of any serious infection or any infection after CD19 CARTx [Time frame: From randomization through day 168 post CARTx]
• Levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG [Time frame: From randomization through day 168 post CARTx]
• Health resource utilization (HRU) [Time frame: Up to 6 months post CARTx]
• Incidence and severity of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS) [Time frame: Up to 6 months post CARTx]
• CAR T-cell expansion: Peak Plasma Concentration (Cmax) [Time frame: Up to 6 months post CARTx]
• CAR T-cell expansion: area under the curve (AUC) [Time frame: Up to 6 months post CARTx]
• CAR T-cell persistence [Time frame: Up to 6 months post CARTx]
• CAR T-cell phenotype and function [Time frame: At day 14 post CARTx]
• Immune cell subset phenotypes and functional makers [Time frame: At 6 months post CARTx]
• IgA and IgM levels [Time frame: At 6 months post CARTx]
• Health related quality of life (HRQOL) [Time frame: From baseline up to 6 months post CARTx]

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

• Note, if there are additional results ≥ 600 mg/dL within the prior three months, but the patient is receiving IVIG, they remain eligible
• 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 for which they underwent CARTx
• SUBSEQUENT INFUSIONS: Receipt of bone marrow transplant (allogeneic or autologous) after CARTx
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Prevention

Study locations

United States · 7 centers

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

Identifiers

NCT: NCT05952804 · RG1123550 · NCI-2023-04889 · 20082 · R01CA276040

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗