IVIG for Infection Prevention After Lymphoma Treatment
Recruiting in Palo Alto (17 mi)
+4 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Fred Hutchinson Cancer Center
Must be taking: CD19-CAR T-cell
Disqualifiers: Selective IgA deficiency, others
Prior Safety Data
Approved in 4 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
Do I need to stop my current medications to join the trial?
The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss your specific situation with the trial team or your doctor.
What data supports the effectiveness of the treatment IVIG for Infection Prevention After Lymphoma Treatment?
Research shows that CD19 CAR-T cell therapy is effective for treating relapsed or refractory lymphoma, although it can increase infection risk. The use of immune globulin infusions (IVIG) may help prevent infections in these patients, as IVIG is known to support the immune system.
12345Is IVIG for infection prevention after lymphoma treatment generally safe?
Anti-CD19 CAR T-cell therapy, which is related to IVIG, has shown potential in treating B-cell malignancies but can cause side effects like increased infection risk and acute neurotoxicity. Some patients experience reversible toxicities linked to inflammation, but these treatments are still considered promising for certain cancers.
16789How is Anti-CD19 CAR-T Cell Therapy different from other treatments for lymphoma?
Anti-CD19 CAR-T Cell Therapy is unique because it uses a patient's own T-cells, which are modified to specifically target and attack cancer cells with the CD19 marker, offering a new option for those with aggressive B-cell lymphomas that do not respond to traditional chemotherapy.
14101112Eligibility Criteria
This trial is for adults with lymphoma who are getting FDA-approved CD19-CAR T-cell therapy and have low levels of IgG antibodies. They must understand the study's risks and benefits, give informed consent, or have a legal representative do so if they're unable to. People with past IVIG issues, serious allergies to IVIG components, or conditions that could risk their safety or skew results can't join.Inclusion Criteria
I have received an FDA-approved CAR T-cell therapy for lymphoma.
I will receive an FDA-approved CAR T-cell therapy for lymphoma.
If I'm unable to consent, my legal representative will sign for me.
+3 more
Exclusion Criteria
Known serious allergy to any component of IVIG
Prior serious adverse event/s related to intravenous immune globulin (IVIG) administration
I have a condition where my body lacks enough IgA antibodies.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2 weeks
1 visit (in-person)
Pre-Treatment
Participants receive either immunoglobulin replacement therapy or placebo within 14 days prior to CD19 CAR-T-cell infusion
2 weeks
1 visit (in-person)
Treatment
Participants undergo CD19 CAR-T-cell therapy and receive monthly infusions of either IVIG or placebo for up to 4 months
4 months
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment, with monthly follow-ups for up to 6 months post CAR-T-cell infusion
6 months
6 visits (in-person)
Participant Groups
The trial is testing whether giving immunoglobulin replacement therapy (IVIG) after CAR-T cell treatment can prevent infections better than a placebo. Participants will either receive human immune globulin infusions or saline as a control while being monitored through surveys and health record reviews.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Arm I (therapeutic immune globulin)Experimental Treatment5 Interventions
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.
Group II: Arm II (normal saline)Placebo Group5 Interventions
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.
Anti-CD19-targeting CAR-T Cells is already approved in United States, European Union, Canada, Japan for the following indications:
🇺🇸 Approved in United States as CAR-T Cell Therapy for:
- B-cell lymphoma
- Acute lymphoblastic leukemia (ALL)
- Multiple myeloma
🇪🇺 Approved in European Union as CAR-T Cell Therapy for:
- Diffuse large B-cell lymphoma (DLBCL)
- Primary mediastinal large B-cell lymphoma (PMBCL)
- Acute lymphoblastic leukemia (ALL)
- Multiple myeloma
🇨🇦 Approved in Canada as CAR-T Cell Therapy for:
- B-cell lymphoma
- Acute lymphoblastic leukemia (ALL)
- Multiple myeloma
🇯🇵 Approved in Japan as CAR-T Cell Therapy for:
- B-cell lymphoma
- Acute lymphoblastic leukemia (ALL)
- Multiple myeloma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutch/University of Washington Cancer ConsortiumSeattle, WA
Memorial Sloan Kettering Cancer CenterNew York, NY
Moffitt Cancer CenterTampa, FL
Massachusetts General Hospital Cancer CenterBoston, MA
More Trial Locations
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Who Is Running the Clinical Trial?
Fred Hutchinson Cancer CenterLead Sponsor
TakedaIndustry Sponsor
National Cancer Institute (NCI)Collaborator
References
Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]CD19 chimeric antigen receptor (CAR)-T cell therapy has emerged as an effective treatment in those with refractory or relapsed lymphoma. CD19 CAR-T cell therapy can cause direct and indirect toxic adverse effects and increased risk for infection. Infectious complications and optimal antimicrobial prophylaxis strategies are an ongoing area of investigation.
Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]Chimeric antigen receptor T (CAR-T) cell therapy, a new adoptive cell therapy, has been widely used to treat lymphoma patients. Immune checkpoint blockade may improve the cytotoxicity of CAR-T cells by reducing the failure of CAR-T cells and improving antitumor activity. It has shown promising efficacy.
Targeting CD79b for Chimeric Antigen Receptor T-Cell Therapy of B-Cell Lymphomas. [2021]Although chimeric antigen receptor (CAR) T-cell therapy targeting antigens expressed in refractory and relapsed non-Hodgkin B-cell lymphoma, such as CD19 and CD22, has achieved encouraging clinical effects, some patients fail to attain remission, or relapse after CAR T-cell therapy, which has been ascribed to the loss of the target antigens.
CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]Cellular immunotherapy with CD19-directed chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for aggressive B-cell non-Hodgkin lymphoma (B-NHL). Three CAR T-cell therapies are commercially avai.
Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. [2022]Chimeric antigen receptor (CAR) T-cell therapy is effective in treating relapsed and refractory B-cell non-Hodgkin lymphoma. However, because of the mortality risk associated with immune effector cell-associated neurotoxicity syndrome and pseudoprogression, patients with central nervous system (CNS) involvement are less likely to receive CAR T-cell therapy.
Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. [2023]Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is a promising treatment in relapsing B-cell lymphoma but is frequently associated with acute neurotoxicity. Neurologic long-term safety has not been thoroughly assessed.
Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. [2021]Most B-cell malignancies express CD19, and a majority of patients with B-cell malignancies are not cured by current standard therapies. Chimeric antigen receptors (CARs) are fusion proteins consisting of antigen recognition moieties and T-cell activation domains. T cells can be genetically modified to express CARs, and adoptive transfer of anti-CD19 CAR T cells is now being tested in clinical trials. Effective clinical treatment with anti-CD19 CAR T cells was first reported in 2010 after a patient with advanced-stage lymphoma treated at the NCI experienced a partial remission of lymphoma and long-term eradication of normal B cells. Additional patients have subsequently obtained long-term remissions of advanced-stage B-cell malignancies after infusions of anti-CD19 CAR T cells. Long-term eradication of normal CD19(+) B cells from patients receiving infusions of anti-CD19 CAR T cells demonstrates the potent antigen-specific activity of these T cells. Some patients treated with anti-CD19 CAR T cells have experienced acute adverse effects, which were associated with increased levels of serum inflammatory cytokines. Although anti-CD19 CAR T cells are at an early stage of development, the potent antigen-specific activity observed in patients suggests that infusions of anti-CD19 CAR T cells might become a standard therapy for some B-cell malignancies.
B-cell depletion and remissions of malignancy along with cytokine-associated toxicity in a clinical trial of anti-CD19 chimeric-antigen-receptor-transduced T cells. [2023]We conducted a clinical trial to assess adoptive transfer of T cells genetically modified to express an anti-CD19 chimeric Ag receptor (CAR). Our clinical protocol consisted of chemotherapy followed by an infusion of anti-CD19-CAR-transduced T cells and a course of IL-2. Six of the 8 patients treated on our protocol obtained remissions of their advanced, progressive B-cell malignancies. Four of the 8 patients treated on the protocol had long-term depletion of normal polyclonal CD19(+) B-lineage cells. Cells containing the anti-CD19 CAR gene were detected in the blood of all patients. Four of the 8 treated patients had prominent elevations in serum levels of the inflammatory cytokines IFNγ and TNF. The severity of acute toxicities experienced by the patients correlated with serum IFNγ and TNF levels. The infused anti-CD19-CAR-transduced T cells were a possible source of these inflammatory cytokines because we demonstrated peripheral blood T cells that produced TNF and IFNγ ex vivo in a CD19-specific manner after anti-CD19-CAR-transduced T-cell infusions. Anti-CD19-CAR-transduced T cells have great promise to improve the treatment of B-cell malignancies because of a potent ability to eradicate CD19(+) cells in vivo; however, reversible cytokine-associated toxicities occurred after CAR-transduced T-cell infusions.
CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives. [2023]While more than half of non-Hodgkin lymphomas (NHL) can be cured with modern frontline chemoimmunotherapy regimens, outcomes of relapsed and/or refractory (r/r) disease in subsequent lines remain poor, particularly if considered ineligible for hematopoietic stem cell transplantation. Hence, r/r NHLs represent a population with a high unmet medical need. This therapeutic gap has been partially filled by adoptive immunotherapy. CD19-directed autologous chimeric antigen receptor (auto-CAR) T cells have been transformative in the treatment of patients with r/r B cell malignancies. Remarkable response rates and prolonged remissions have been achieved in this setting, leading to regulatory approval from the U.S. Food and Drug Administration (FDA) of four CAR T cell products between 2017 and 2021. This unprecedented success has created considerable enthusiasm worldwide, and autologous CAR T cells are now being moved into earlier lines of therapy in large B cell lymphoma. Herein, we summarize the current practice and the latest progress of CD19 auto-CAR T cell therapy and the management of specific toxicities and discuss the place of allogeneic CAR T development in this setting.
Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]CAR T-cells are autologous T-cells transduced with a chimeric antigen receptor which targets the modified T-cell against a specified cancer antigen. Anti-CD19 CAR T-cells currently represent transformational therapy for relapsed/refractory aggressive B-cell lymphomas where durable remissions can be induced in patients with previously incurable chemotherapy-refractory disease. Three anti-CD19 CAR T-cells are currently Food and Drug Administration and European Medicines Agency approved or in advanced-stage development: axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel. Although all targeting CD19 on the surface of malignant (and healthy) B-cells, these products differ from one another in multiple ways including construct, manufacturing, dose, design of pivotal clinical trials, and toxicity profile. Efficacy and safety data for anti-CD19 CAR T-cell therapy in aggressive B-cell lymphomas will be reviewed, as well as novel CAR T-cell designs and strategies for overcoming treatment resistance.
Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. [2022]Anti-CD19 CAR-T cell therapy is effective in B-cell lymphoma. However, it is rarely used in lymphoma combined with other malignant tumours.
Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy. [2017]Immunotherapy for B-cell lymphomas has evolved significantly with the advent of CD20-targeted Ab-based therapeutics. Strategies to invoke or augment cellular anti-lymphoma immune responses may also have considerable therapeutic potential and serve to further augment the clinical efficacy of MAbs.