Immunoglobulin Replacement Therapy and Infectious Complications After CD19-Targeted CAR-T-Cell Therapy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 11
- 主要终点
- Incidence rate of serious bacterial infections in the modified intention-to-treat (mITT) population
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants and study staff (except for site pharmacists) will be blinded to treatment arm assignments.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Arm I (therapeutic immune globulin)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Immune Globulin Infusion (Human), 10% Solution (Biological)
Arm I (therapeutic immune globulin)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Anti-CD19 CAR T Cells Preparation (Biological)
Arm I (therapeutic immune globulin)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm I (therapeutic immune globulin)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Survey Administration (Other)
Arm I (therapeutic immune globulin)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Electronic Health Record Review (Other)
Arm II (normal saline)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Anti-CD19 CAR T Cells Preparation (Biological)
Arm II (normal saline)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Saline (Other)
Arm II (normal saline)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection (Procedure)
Arm II (normal saline)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Survey Administration (Other)
Arm II (normal saline)
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. Doses 3, 4, and 5 are highly encouraged but not required. Patients also undergo blood sample collection throughout the study.
干预措施: Electronic Health Record Review (Other)
结局指标
主要结局
Incidence rate of serious bacterial infections in the modified intention-to-treat (mITT) population
时间窗: From randomization through day 168 post chimeric antigen receptor (CAR) T-cell treatment (CARTx)
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.
次要结局
- 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: area under the curve (AUC)(Up to 6 months post CARTx)
- 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)
- Health related quality of life (HRQOL)(From baseline up to 6 months post CARTx)
- CAR T-cell expansion: Peak Plasma Concentration (Cmax)(Up to 6 months post CARTx)
- CAR T-cell persistence(Up to 6 months post CARTx)
- CAR T-cell phenotype and function(At day 14 post CARTx)
- Immune cell subset phenotypes and functional makers(At 6 months post CARTx)
- IgA and IgM levels(At 6 months post CARTx)