Clinical trial NCT05952804: IVIG for Infection Prevention After CAR-T-Cell Therapy
Official title: Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Hematologic Malignancies
Lead sponsor: Fred Hutchinson Cancer Center
Sponsor class: OTHER
Collaborators: name: Takeda
name: National Cancer Institute (NCI)
First posted: 2023-07-19
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

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

Primary outcomes:
measure: Incidence rate of serious bacterial infections in the modified intention-to-treat (mITT) population
timeFrame: From randomization through day 168 post chimeric antigen receptor (CAR) T-cell treatment (CARTx)
Secondary outcomes:
measure: Incidence rate of serious bacterial infections in ITT and per-protocol populations and of any serious infection or any infection after CD19 CARTx
timeFrame: From randomization through day 168 post CARTx
measure: Levels of total IgG, IgG subclasses, and total Streptococcus (S.) pneumoniae IgG
timeFrame: From randomization through day 168 post CARTx
measure: Health resource utilization (HRU)
timeFrame: Up to 6 months post CARTx
measure: Incidence and severity of cytokine release syndrome (CRS) and/or immune effector cell-associated neurotoxicity syndrome (ICANS)
timeFrame: Up to 6 months post CARTx
measure: CAR T-cell expansion: Peak Plasma Concentration (Cmax)
timeFrame: Up to 6 months post CARTx
measure: CAR T-cell expansion: area under the curve (AUC)
timeFrame: Up to 6 months post CARTx
measure: CAR T-cell persistence
timeFrame: Up to 6 months post CARTx
measure: CAR T-cell phenotype and function
timeFrame: At day 14 post CARTx
measure: Immune cell subset phenotypes and functional makers
timeFrame: At 6 months post CARTx
measure: IgA and IgM levels
timeFrame: At 6 months post CARTx
measure: Health related quality of life (HRQOL)
timeFrame: From baseline up to 6 months post CARTx
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Cancer Center
state: California
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Boston
country: United States
facility: Massachusetts General Hospital Cancer Center
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Seattle
country: United States
facility: Fred Hutch/University of Washington Cancer Consortium
state: Washington
Study officials:
affiliation: Fred Hutch/University of Washington Cancer Consortium
name: Joshua Hill, MD
role: PRINCIPAL_INVESTIGATOR
References: