IVIG for Infection Prevention After Lymphoma Treatment

Recruiting at 4 trial locations

Overseen By Joshua A. Hill

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Fred Hutchinson Cancer Center

Must be taking: CD19-CAR T-cell

Disqualifiers: Selective IgA deficiency, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

Duration: 4 months

150 Participants Needed

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. ^{1 2 3 4 5}

Is 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. ^{1 6 7 8 9}

How 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. ^{1 4 10 11 12}

Research Team

Joshua A. Hill

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility 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.

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.

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)

Treatment Details

Interventions

• Anti-CD19-targeting CAR-T Cells
• Immune Globulin Infusion (Human), 10% Solution

Trial Overview 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.

Participant Groups

Group I: Arm I (therapeutic immune globulin) Experimental Treatment 5 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 Group 5 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

Who Is Running the Clinical Trial?

Fred Hutchinson Cancer Center

Lead Sponsor

Trials

583

Recruited

1,341,000+

Takeda

Industry Sponsor

Trials

1,255

Recruited

4,219,000+

Dr. Naoyoshi Hirota

Takeda

Chief Medical Officer since 2020

MD from University of Tokyo

Christophe Weber

Takeda

Chief Executive Officer since 2015

PhD in Molecular Biology from Université de Montpellier

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

In a study of 50 patients receiving CD19 CAR-T cell therapy, 36% experienced infectious complications, with a median time to infection of 225 days, indicating that infections can occur well after treatment.

Severe infections were common, with 54.8% leading to significant health issues, including hospitalization and even death in 6% of patients, highlighting the need for ongoing monitoring and improved antimicrobial prophylaxis strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. Walker, B., Zimmer, AJ., Stohs, EJ., et al.[2023]

CAR-T cell therapy combined with anti-PD-1 immunotherapy shows promising efficacy in treating lymphoma, with an overall response rate of 65% based on an analysis of 57 patients from 5 clinical trials.

The most common adverse effect observed was fever, with a pooled incidence of 59%, indicating that while the therapy is effective, it does come with notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. Zhou, Y., Mu, W., Wang, C., et al.[2023]

CD79b is widely expressed on tumor cells in various types of B-cell lymphomas, making it a promising target for CAR T-cell therapy.

Anti-CD79b CAR T-cells demonstrated high specificity and effectiveness in treating B-cell lymphomas, suggesting that targeting CD79b could improve outcomes for patients who do not respond to existing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD79b for Chimeric Antigen Receptor T-Cell Therapy of B-Cell Lymphomas. Ding, S., Mao, X., Cao, Y., et al.[2021]

CD19-directed CAR T-cell therapy has significantly transformed the treatment approach for aggressive B-cell non-Hodgkin lymphoma, offering new hope for patients.

There are currently three commercially available CAR T-cell therapies targeting CD19, indicating a growing acceptance and application of this innovative immunotherapy in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. Gideon, J.[2023]

A 61-year-old male patient with intravascular large B-cell lymphoma and CNS involvement achieved complete remission after receiving CAR T-cell therapy following a conditioning regimen and autologous stem cell transplantation.

The treatment was associated with only mild side effects, specifically grade 1 cytokine release syndrome, and no serious adverse events like neurotoxicity or pseudoprogression, suggesting that CAR T-cell therapy can be safely administered to patients with CNS involvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. Yagi, Y., Kanemasa, Y., Ohigashi, A., et al.[2022]

In a study of 19 patients with relapsing B-cell lymphoma who received anti-CD19 CAR T-cell therapy, no new neurologic deficits or changes in brain MRI were observed two years post-treatment, indicating long-term neurologic safety.

Cognitive performance remained stable over the two years, even in patients who experienced acute neurotoxicity, and there was a significant reduction in anxiety scores, suggesting overall improvement in mental health after treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. Ursu, R., Maillet, D., Belin, C., et al.[2023]

Anti-CD19 CAR T cell therapy has shown promising results in treating advanced-stage B-cell malignancies, with some patients achieving long-term remissions after treatment, indicating its potential as a new standard therapy.

While the therapy demonstrates strong efficacy by specifically targeting CD19, some patients have experienced acute adverse effects linked to increased inflammatory cytokines, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. Kochenderfer, JN., Rosenberg, SA.[2021]

In a clinical trial involving 8 patients with advanced B-cell malignancies, 6 achieved remission after receiving T cells genetically modified to target CD19, indicating the efficacy of this CAR T-cell therapy.

While the treatment showed promise in eradicating CD19(+) cells, patients experienced reversible toxicities associated with elevated inflammatory cytokines (IFNγ and TNF), suggesting a need for monitoring and managing these side effects during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Kochenderfer, JN., Dudley, ME., Feldman, SA., et al.[2023]

CD19-directed autologous CAR T cell therapy has shown remarkable effectiveness in treating relapsed and refractory non-Hodgkin lymphoma (NHL), leading to significant response rates and prolonged remissions, which has resulted in FDA approval for four CAR T cell products from 2017 to 2021.

Due to its success, there is growing interest in using autologous CAR T cells earlier in treatment for large B cell lymphoma, highlighting the need for ongoing management of associated toxicities and the exploration of allogeneic CAR T options.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives. Sheikh, S., Migliorini, D., Lang, N.[2023]

Anti-CD19 CAR T-cell therapy has shown remarkable efficacy in treating relapsed or refractory aggressive B-cell lymphomas, leading to durable remissions in patients who previously had no effective treatment options.

Three CAR T-cell therapies (axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel) are approved for use, each differing in their design, manufacturing processes, and safety profiles, highlighting the need for personalized approaches in cancer treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. Abramson, JS.[2021]

Anti-CD19 CAR-T cell therapy successfully achieved a complete response in a patient with relapsed/refractory follicular lymphoma, demonstrating its efficacy in treating this type of lymphoma.

The therapy not only addressed the lymphoma but also allowed for subsequent curative treatment of gastric adenocarcinoma, indicating its potential for use in patients with multiple malignancies while maintaining a good quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. Liu, J., Cao, F., Li, Z., et al.[2022]

Genetically modified human T-cells expressing a chimeric immunoreceptor targeting CD20 can effectively kill lymphoma cells, demonstrating a new approach to enhance anti-lymphoma immune responses.

These engineered T-cells not only kill CD20+ lymphoma cells but also produce important cytokines like IFN-gamma and proliferate in response to lymphoma stimulators, suggesting their potential as a powerful immunotherapy for treating B-cell lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy. Jensen, MC., Cooper, LJ., Wu, AM., et al.[2017]

References

1. Denmark pubmed.ncbi.nlm.nih.gov

Infectious complications among CD19 CAR-T cell therapy recipients: A single-center experience. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Ray of dawn: Anti-PD-1 immunotherapy enhances the chimeric antigen receptor T-cell therapy in Lymphoma patients. [2023]

3. France pubmed.ncbi.nlm.nih.gov

Targeting CD79b for Chimeric Antigen Receptor T-Cell Therapy of B-Cell Lymphomas. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

CAR T-Cell Therapy for Relapsed/Refractory Aggressive Large B-Cell Lymphoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapy following autologous transplantation for secondary central nervous system lymphoma: A case report. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Long-term Neurologic Safety in Patients With B-Cell Lymphoma Treated With Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy. [2023]

7. England pubmed.ncbi.nlm.nih.gov

Treating B-cell cancer with T cells expressing anti-CD19 chimeric antigen receptors. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

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]

9. Switzerland pubmed.ncbi.nlm.nih.gov

CAR T-Based Therapies in Lymphoma: A Review of Current Practice and Perspectives. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Anti-CD19 CAR T-Cell Therapy for B-Cell Non-Hodgkin Lymphoma. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Successful treatment of a case with synchronous follicular lymphoma and gastric adenocarcinoma with CD19 CAR T cells and literature review. [2022]

12. England pubmed.ncbi.nlm.nih.gov

Engineered CD20-specific primary human cytotoxic T lymphocytes for targeting B-cell malignancy. [2017]