CAR T-Cell Therapy for Lymphoma and Leukemia

Overseen By Nasheed M. Hossain

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Loyola University

Must not be taking: Anticoagulants, Immunosuppressants

Disqualifiers: Infections, Cardiac disease, Autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for creating CAR T-cells, a promising treatment for certain blood cancers like lymphoma and leukemia. The researchers aim to determine if these specially crafted cells can work more effectively and cause fewer side effects. Participants are divided into groups to test various doses of these modified T-cells. This study may suit those with aggressive or recurring B-cell non-Hodgkin lymphoma or B-cell acute lymphoblastic leukemia that hasn't responded to other treatments. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications. However, there is a washout period (time without taking certain medications) of at least 2 weeks or 5 half-lives since any prior systemic therapy, except for certain immune therapies which require 5 half-lives.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that CD19 CAR T-cell therapies have been tested in various studies to assess their safety in humans. In studies involving patients with relapsed or hard-to-treat cancers, CD19 CAR T-cells have shown promise as a backup treatment. However, some side effects have been reported. Common side effects include fever and low blood pressure. More serious side effects, such as cytokine release syndrome (a severe inflammatory response), can occur but are less common.

One study found that patients with conditions like systemic lupus erythematosus (SLE) experienced less severe side effects compared to those with certain types of lymphoma. This suggests that reactions to the treatment can vary based on the patient's condition. Overall, while CD19 CAR T-cell therapy shows potential, it is important to consider these risks. Participants should discuss possible side effects with their healthcare team to understand what to expect. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about CAR T-cell therapy for lymphoma and leukemia because it represents a groundbreaking approach to treatment. Unlike traditional therapies such as chemotherapy and radiation, which broadly attack cancer cells and can damage healthy cells, CAR T-cell therapy is highly targeted. It involves modifying a patient's own T-cells to better identify and destroy cancer cells, specifically those expressing the CD19 antigen. This personalized and precise mechanism has the potential to improve effectiveness and reduce side effects compared to conventional treatments. Additionally, CAR T-cell therapy offers the hope of long-lasting remission, as these engineered T-cells can persist in the body and continue to fight cancer cells.

What evidence suggests that this trial's treatments could be effective for lymphoma and leukemia?

Research has shown that CD19 CAR T-cell therapy, which participants in this trial may receive, offers promising results for treating certain blood cancers like lymphoma and leukemia. In one study, many patients with B-cell lymphoma experienced long-lasting remission, with some remissions lasting over three years. Another study found that 66.7% to 92.9% of patients responded to the treatment, depending on the type of lymphoma, meaning a significant number of patients saw their cancer shrink or disappear. These findings suggest CD19 CAR T-cell therapy could be a powerful option for those fighting these types of cancers. ^{6 7 8 9 10}

Who Is on the Research Team?

Nasheed M. Hossain

Principal Investigator

Loyola University

Are You a Good Fit for This Trial?

Adults over 18 with certain aggressive B-cell blood cancers that have come back or didn't respond to treatment. They must be in good physical shape, with well-functioning organs and bone marrow. Pregnant women can't join, and participants should not have severe heart issues, active infections like HIV/HBV/HCV, a history of significant autoimmune diseases within the last two years, or any recent serious allergic reactions to similar drugs.

Inclusion Criteria

It's been over 2 weeks or 5 half-lives since my last systemic therapy, except for immune therapy.

My B-ALL cancer has not responded to treatment or has come back.

My aggressive B cell NHL has come back or is not responding to treatment.

Exclusion Criteria

I haven't had a heart attack or other major heart issues in the last year.

I have been cancer-free for at least a year, except for non-melanoma skin cancer or certain in situ cancers.

I do not have any active infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Leukapheresis

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day

1 day

Lymphodepletion

Participants receive daily intravenous infusion of fludarabine and cyclophosphamide for a total of 3 days

3 days

CAR T Cell Infusion

Participants receive CAR transduced T cells IV infusion and remain admitted for close monitoring for at least the first 7 days following the cell infusion

7 days

Initial Monitoring

Participants are evaluated in the High Dose Unit for toxicities for the next 7 days after discharge from the inpatient unit

7 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• CD19 Chimeric Antigen Receptor (CAR) T Cells

Trial Overview The trial is testing a new way to make CAR T-cells using CD19-CD34 proteins. These are special immune cells designed in the lab to fight cancer better and with fewer side effects than previous methods. Patients will also receive chemotherapy drugs Cyclophosphamide and Fludarabine before getting these modified T-cells.

How Is the Trial Designed?

Group I: CAR 5 x 105 transduced T cells/kg (Dose Level -1) Experimental Treatment 3 Interventions

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 5 x 105 transduced T cells/kg.

Group II: CAR 2 x 106 transduced T cells/kg (Dose Level 3) Experimental Treatment 3 Interventions

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 2 x 106 transduced T cells/kg.

Group III: CAR 1.5 x 106 transduced T cells/kg (Dose Level 2) Experimental Treatment 3 Interventions

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 1.5 x 106 transduced T cells/kg.

Group IV: CAR 1 x 106 transduced T cells/kg (Dose Level 1) Experimental Treatment 3 Interventions

Autologous peripheral blood mononuclear cell (PBMC) will be obtained by leukapheresis over one day. Daily intravenous (IV) infusion of fludarabine and cyclophosphamide for total of 3 days (Days -5, -4, -3). The dose of cyclophosphamide will be given at 500mg/m2. The dose of fludarabine will be given at 30mg/m2. CD19-CD34 CAR transduced T cells will be administered IV at a dose level of 1 x 106 transduced T cells/kg.

Who Is Running the Clinical Trial?

Loyola University

Lead Sponsor

Trials

161

Recruited

31,400+

Leukemia Research Foundation

Collaborator

Trials

1

Recruited

20+

Published Research Related to This Trial

CAR-T cell therapy has shown remarkable efficacy in treating B cell malignancies, including leukemia, lymphoma, and multiple myeloma, with high response rates, but it comes with significant safety concerns.

The most serious side effects of CAR-T therapy are cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), which require supportive care and specific treatments like tocilizumab and steroids to manage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T Cell Therapy: the Efficacy and Toxicity Balance. Chohan, KL., Siegler, EL., Kenderian, SS.[2023]

CAR T-cells are engineered T-cells that target the CD19 antigen, showing promising initial results in treating various B-cell malignancies, including acute lymphocytic leukaemia and chronic lymphocytic leukaemia.

While the treatment shows potential, there are significant differences in patient responses and notable side effects that require careful management, highlighting the need for personalized approaches in therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. Heijink, DM., Kater, AP., Hazenberg, MD., et al.[2017]

CAR T-cell therapy is a groundbreaking treatment for recurrent B-cell lymphomas and acute lymphoid leukemia, showing over 80% remission rates and faster responses compared to traditional therapies, with a treatment duration of just 2-3 weeks.

While CAR T-cell therapy can lead to significant side effects like cytokine release syndrome and neurotoxicity, understanding these potential adverse events and their timelines is crucial for optimizing patient care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Imaging Primer on Chimeric Antigen Receptor T-Cell Therapy for Radiologists. de Groot, PM., Arevalo, O., Shah, K., et al.[2022]

Chimeric antigen receptor (CAR) therapy, particularly targeting CD19, has shown significant efficacy in treating patients with chemorefractory B cell malignancies, leading to its potential regulatory approval as a cell-based immunotherapy.

While CAR therapy is effective, it is associated with toxicities such as cytokine release syndrome, neurotoxicity, and B cell aplasia, which require careful management in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. Davila, ML., Sadelain, M.[2023]

CAR T-cell therapy is becoming a groundbreaking treatment for aggressive non-Hodgkin B-cell lymphoma, showing promise in improving patient outcomes.

The review discusses not only the efficacy of CAR T-cell therapy but also highlights the potential short- and long-term toxicities associated with the treatment, emphasizing the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. Hamilton, MP., Miklos, DB.[2023]

Chimeric antigen receptor (CAR)-modified T cells are a promising living immunotherapy that can effectively treat various diseases, particularly refractory cancers like leukemia and lymphoma.

Recent advancements in CAR design and T cell manufacturing have improved the clinical management of patients, leading to lasting remissions and establishing CAR T cell therapy as a leading treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances and Challenges of CAR T Cells in Clinical Trials. Holzinger, A., Abken, H.[2019]

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 is an effective treatment for acute lymphocytic leukemia and B-cell lymphoma, but it requires at least 7 days of hospitalization to monitor for serious side effects like cytokine release syndrome and neurotoxicity.

Early identification and treatment of these toxicities by nursing staff can reverse potentially life-threatening complications, highlighting the importance of objective assessment and consensus grading in managing CAR T-cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Emergencies: Inpatient Administration, Assessment, and Management. Jackson, S., Wheatley, T.[2021]

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]

CD19-directed CAR T-cell therapy has significantly improved survival rates for patients with high-risk B-cell non-Hodgkin lymphoma, showcasing its efficacy as a treatment option.

The article highlights ongoing research into the toxicity risks associated with CAR T-cell therapy, as well as strategies to mitigate these risks and address challenges like treatment resistance and global access to this innovative therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cellular therapy in lymphoma. Sureda, A., Lugtenburg, PJ., Kersten, MJ., et al.[2023]

CAR T cell therapy targeting CD19 has shown remarkable efficacy, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), compared to a 30% response rate with traditional chemotherapy.

The therapy involves genetically modifying T cells to express a chimeric antigen receptor, allowing them to effectively target and eliminate cancer cells, although it is important to note that there are unique toxicities associated with this treatment that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. Davila, ML., Brentjens, RJ.[2023]

Adoptive cellular therapy using CAR-modified T cells targeting CD19 has shown significant clinical efficacy in treating relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL) in both children and adults, with some patients also benefiting from treatment for chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin lymphoma (B-NHL).

Current research is expanding the use of CAR T-cell therapies to other cancers, including multiple myeloma and solid tumors, while also addressing challenges such as severe cytokine release syndrome and neurologic toxicities associated with the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. Geyer, MB., Brentjens, RJ.[2022]

In a Phase I trial involving 43 pediatric and young adult patients with leukemia, initial treatment failures were linked to poor CAR T cell expansion and rapid loss of functional CAR T cells after infusion.

For patients who achieved remission, the durability of that remission was associated with higher levels of TNF-α-secreting CAR CD8+ T cells and sufficient CD19 antigen levels at the time of treatment, suggesting these factors could help predict treatment success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19 CAR T cell product and disease attributes predict leukemia remission durability. Finney, OC., Brakke, HM., Rawlings-Rhea, S., et al.[2022]

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]

Citations

1. nature.com nature.com/articles/s41571-023-00754-1

Long-term outcomes following CAR T cell therapy Long-term follow-up data indicate that CD19-targeted CAR T cells are likely to be curative for a subset of patients with B cell lymphomas. These ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7655016/

Long-Term Follow-Up of Anti-CD19 Chimeric Antigen ... Our data demonstrate that anti-CD19 CAR T-cell treatment often leads to highly durable remissions in patients with B-cell lymphoma that are ongoing up to 113 ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723011314

Outcomes of CD19-Directed Chimeric Antigen Receptor T ... The overall response and complete response rates were 66.7% and 55.6%, respectively, for tCLL/SLL and 92.9% and 71.4% for tMZL. The overall response and ...

4. mdpi.com mdpi.com/2673-6357/6/1/3

Real-World Outcomes of Anti-CD19 Chimeric Antigen ... We report on 82 patients with R/R DLBCL that successfully completed an infusion of an anti-CD19 CAR T-cell product at our institution.

5. haematologica.org haematologica.org/article/view/11872

Five-year outcome of CD19 followed by CD22 chimeric ... Regarding the long-term survival after CD19 CAR T-cell therapy, recent investigations showed an EFS of 44% and OS of 63% at 3 years in young adult and pediatric ...

6. nature.com nature.com/articles/s41409-025-02691-2

Safety and efficacy of autologous humanized CD19 CAR-T ... Safety and efficacy of a humanized CD19 chimeric antigen receptor T cells for relapsed/refractory acute lymphoblastic leukemia. Am J Hematol ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03233854

NCT03233854 | CD19/CD22 Chimeric Antigen Receptor ... This phase I trial studies the side effects of CD19/CD22 chimeric antigen receptor (CAR) T cells when given together with chemotherapy and NKTR-255, ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7575989/

Efficacy and safety of CD19 chimeric antigen receptor T cells ... The above data suggest that CD19 CAR T product is an effective rescue treatment for relapsed and refractory B-cell lymphoma (20). However, the adverse reactions ...

9. ashpublications.org ashpublications.org/blood/article/146/9/1088/537757/Comparison-of-the-safety-profiles-of-CD19

Comparison of the safety profiles of CD19-targeting CAR T ... Despite similar CAR T-cell dynamics, patients with SLE experienced less severe adverse events after CAR T-cell therapy than those with B-NHL ...

10. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2830583

Adverse Events After CAR T-Cell Therapy in B-Cell Non- ... This cohort study assesses the occurrence of late adverse events for adult patients with aggressive large B-cell non-Hodgkin lymphoma ...