IVIG for Infection Prevention After CAR-T-Cell Therapy

NCT05952804 | Recruiting Phase 2 DMC FDA Drug

• 4 other identifiers: RG1123550NCI-2023-0488920082R01CA276040
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 7

Brief 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.

Conditions

Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• Incidence rate of serious bacterial infections in the modified intention-to-treat (mITT) population

  Grade 2 or 3 bacterial infections. Only microbiologically confirmed infections will be included. Microbiological documentation of an infection consists of isolation of the pathogen by culture from a sterile (definite) or nonsterile (probable) site (if from a nonsterile site, the organism had to be clinically judged to be pathogenic). Will describe the number and type of infections in each study arm and calculate incidence rate estimates and 95% confidence intervals (CIs) for infections. Will compare serious bacterial infection incidence rates between study arms using negative binomial regression with an offset to account for days-at-risk. Will construct multivariable Cox proportional hazards models of time-to-first serious bacterial infection.

  From randomization through day 168 post chimeric antigen receptor (CAR) T-cell treatment (CARTx)

Secondary Outcomes (11)

• Incidence rate of serious bacterial infections in ITT and per-protocol populations and of any serious infection or any infection after CD19 CARTx

  From randomization through day 168 post CARTx

• Levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG

  From randomization through day 168 post CARTx

• Health resource utilization (HRU)

  Up to 6 months post CARTx

• Incidence and severity of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS)

  Up to 6 months post CARTx

• CAR T-cell expansion: Peak Plasma Concentration (Cmax)

  Up to 6 months post CARTx

Study Arms (2)

Arm I (therapeutic immune globulin)

EXPERIMENTAL

Patients receive IGRT with IVIG within 14 days prior to CD19 CAR-T treatment. Patients then undergo CD19 CAR-T therapy. Patients receive IVIG monthly, starting 28 days after CD19 CAR-T therapy for 4 months in the absence of unacceptable toxicity. Patients also undergo blood sample collection throughout the study.

Biological: Immune Globulin Infusion (Human), 10% Solution; Biological: Anti-CD19 CAR T Cells Preparation; Procedure: Biospecimen Collection; Other: Survey Administration; Other: Electronic Health Record Review

Arm II (normal saline)

PLACEBO COMPARATOR

Patients receive placebo with normal saline IV within 14 days prior to CD19 CAR-T treatment. Patients then undergo CD19 CAR-T therapy. Patients receive normal saline monthly, starting 28 days after CD19 CAR-T therapy for 4 months in the absence of unacceptable toxicity. Patients also undergo blood sample collection throughout the study.

Biological: Anti-CD19 CAR T Cells Preparation; Other: Saline; Procedure: Biospecimen Collection; Other: Survey Administration; Other: Electronic Health Record Review

Interventions

Immune Globulin Infusion (Human), 10% Solution BIOLOGICAL

Given IV

Also known as: GAMMAGARD LIQUID

Arm I (therapeutic immune globulin)

Anti-CD19 CAR T Cells Preparation BIOLOGICAL

Given CAR-T treatment

Also known as: CD19-targeting CAR-T Cells

Arm I (therapeutic immune globulin); Arm II (normal saline)

Saline OTHER

Given IV

Also known as: 7647-14-5, ISOTONIC SODIUM CHLORIDE SOLUTION, Sodium Chloride 0.9%

Arm II (normal saline)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected

Arm I (therapeutic immune globulin); Arm II (normal saline)

Survey Administration OTHER

Ancillary studies

Arm I (therapeutic immune globulin); Arm II (normal saline)

Electronic Health Record Review OTHER

Ancillary studies

Arm I (therapeutic immune globulin); Arm II (normal saline)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Fred Hutchinson Cancer Center: lead
• Takeda: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (7)

City of Hope Cancer Center

Duarte, California, 91010, United States

RECRUITING

University of Miami Miller School of Medicine-Sylvester Cancer Center

Miami, Florida, 33136, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

RECRUITING

Massachusetts General Hospital Cancer Center

Boston, Massachusetts, 02114, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Oregon Health and Science University (OHSU) Knight Cancer Institute

Portland, Oregon, 97239, United States

RECRUITING

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

RECRUITING

MeSH Terms

Conditions

Hematologic Neoplasms

Interventions

Solutions; Sodium Chloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Joshua Hill, MD

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Joshua Hill, MD

CONTACT

206-667-6504; jahill@fredhutch.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Participants and study staff (except for site pharmacists) will be blinded to treatment arm assignments.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 6, 2023
• First Posted: July 19, 2023
• Study Start: June 10, 2024
• Primary Completion (Estimated): July 31, 2028
• Study Completion (Estimated): July 31, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)