Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy
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.
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. 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.
Arms & interventions
- BiologicalImmune Globulin Infusion (Human), 10% Solution
Given IV
- BiologicalAnti-CD19 CAR T Cells Preparation
Given CAR-T treatment
- OtherSaline
Given IV
- ProcedureBiospecimen Collection
Undergo blood sample collection
- OtherSurvey Administration
Ancillary studies
- OtherElectronic Health Record Review
Ancillary studies
Outcome measures
Primary
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.
Time frame: From randomization through day 168 post chimeric antigen receptor (CAR) T-cell treatment (CARTx)
Secondary
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
Study locations (7)
City of Hope Cancer Center
Duarte, California, 91010
University of Miami Miller School of Medicine-Sylvester Cancer Center
Miami, Florida, 33136
Moffitt Cancer Center
Tampa, Florida, 33612
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Oregon Health and Science University (OHSU) Knight Cancer Institute
Portland, Oregon, 97239
Fred Hutch/University of Washington Cancer Consortium
Seattle, Washington, 98109