CAR-T Cell Therapy for Lymphoma and Leukemia

Overseen By Jacob Naparstek

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jonsson Comprehensive Cancer Center

Must not be taking: Systemic corticosteroids, Immunosuppressive drugs

Disqualifiers: HIV, Hepatitis B/C, Brain metastases, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 18

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the side effects of a new therapy that combines chemotherapy with CAR-T cell therapy for certain types of lymphoma and leukemia. CAR-T cell therapy modifies a patient's white blood cells to target and fight cancer cells more effectively. The trial seeks individuals with types of B-cell lymphoma or chronic lymphocytic leukemia that have returned or not responded to other treatments. Participants should have undergone several rounds of other treatments and still have active disease. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Do I need to stop my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot have received systemic cancer treatment, including immunotherapy, within 14 days before starting the trial's chemotherapy. It's best to discuss your current medications with the study team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that CD19/CD20 CAR-T cell therapy could effectively treat certain types of lymphoma and leukemia. Studies have found that these specially modified T cells can target and attack cancer cells. In earlier research, patients with hard-to-treat non-Hodgkin lymphoma experienced strong and lasting positive responses. The treatment's safety appears promising, with most patients experiencing only mild to moderate side effects. Some patients developed cytokine release syndrome (CRS), a common reaction to this type of treatment, but severe cases were rare. Importantly, no patients experienced severe nerve-related side effects. Overall, these findings suggest that CD19/CD20 CAR-T cells are generally well-tolerated, though they come with potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CAR-T cell therapy for lymphoma and leukemia because it offers a new way to fight these cancers by using the body's own immune system. Unlike traditional chemotherapy or radiation, this treatment involves engineering a patient's T-cells to specifically target and destroy cancer cells, focusing on proteins like CD19 and CD20 found on cancer cells. This personalized approach has the potential to be more effective and cause fewer side effects than standard treatments, as it hones in on the cancer cells while sparing healthy ones.

What evidence suggests that CD19/CD20 CAR-T cells might be an effective treatment for lymphoma and leukemia?

Research has shown that CD19/CD20 CAR-T cell therapy, which participants in this trial will receive, holds promise for treating certain blood cancers. Specifically, studies have found that these specially modified cells can effectively locate and destroy cancer cells in conditions like B-cell non-Hodgkin lymphoma. In one study, 79% of patients with relapsed or hard-to-treat non-Hodgkin lymphoma responded to the treatment. These CAR-T cells are designed to recognize specific proteins on cancer cells, aiding the immune system in fighting the disease. In this trial, participants will receive CD19/CD20 CAR-T cells following conditioning chemotherapy with fludarabine and cyclophosphamide, which may enhance the therapy's effectiveness. This approach aims to increase the chances of remission and reduce the risk of cancer returning. ^{1 2 5 6 7}

Who Is on the Research Team?

Sarah Larson, MD

Principal Investigator

UCLA / Jonsson Comprehensive Cancer Center

Are You a Good Fit for This Trial?

This trial is for adults with certain types of B-cell lymphoma or chronic lymphocytic leukemia that haven't improved after standard treatments. Participants need to have a specific level of organ function, blood cell counts within set ranges, and at least 30% of their cancer cells must express CD19 or CD20 proteins.

Inclusion Criteria

Must be willing and able to provide written informed consent

Total bilirubin =< 2 x ULN (except patients with documented Gilbert's syndrome) (within 30-60 days prior to enrollment)

My cancer did not respond to initial treatment or has come back after 3+ treatments.

Exclusion Criteria

I may need or have recently taken steroids or drugs that weaken my immune system.

My cervical cancer was treated and shows no signs of being present.

My cancer was treated to be cured and currently shows no active signs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Conditioning Chemotherapy

Patients receive fludarabine phosphate and cyclophosphamide intravenously 5, 4, and 3 days before cell infusion

1 week

3 visits (in-person)

T-Cell Infusion

Patients receive CD19/CD20 CAR-T cells intravenously on day 0. Tocilizumab may be administered for cytokine release syndrome

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 15 years

Daily for 14 days, then on days 30, 45, 60, 70, 90, and 120, every 3 months for 2 years, every 6 months for 3 years, and then annually

What Are the Treatments Tested in This Trial?

Interventions

• CD19/CD20 CAR-T Cells

Trial Overview The trial tests modified immune cells (CD19/CD20 CAR-T Cells) combined with chemotherapy drugs cyclophosphamide and fludarabine phosphate. It aims to find the safest dose and see how effective this treatment is against recurrent or refractory non-Hodgkin's B-cell lymphoma or chronic lymphocytic leukemia.

How Is the Trial Designed?

Group I: Treatment (fludarabine, cyclophosphamide, CD19/CD20 T-cells) Experimental Treatment 4 Interventions

CONDITIONING CHEMOTHERAPY: Patients receive fludarabine phosphate IV over 30 minutes and cyclophosphamide IV over 60 minutes 5, 4, and 3 days before cell infusion. T-CELL INFUSION: Patients receive CD19/CD20 CAR-T cells IV on day 0. Patients with cytokine release syndrome may also receive tocilizumab IV on day 2 at the discretion of the clinical investigator.

CD19/CD20 CAR-T Cells is already approved in United States, European Union for the following indications:

Approved in United States as CD19/CD20 CAR-T Cells for:

• Recurrent or Refractory B-Cell Lymphoma
• Chronic Lymphocytic Leukemia

Approved in European Union as CD19/CD20 CAR-T Cells for:

• Recurrent or Refractory B-Cell Lymphoma
• Chronic Lymphocytic Leukemia

Who Is Running the Clinical Trial?

Jonsson Comprehensive Cancer Center

Lead Sponsor

Trials

373

Recruited

35,200+

Parker Institute for Cancer Immunotherapy

Collaborator

Trials

12

Recruited

460+

Published Research Related to This Trial

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 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]

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]

CAR-T cell therapy has shown significant success in treating CD19-positive B-cell cancers, but this review explores its potential in other blood cancers, particularly Hodgkin's lymphoma and acute myeloid leukemia.

The focus on hematologic malignancies beyond CD19 highlights the expanding applications of CAR-T cell technology, suggesting it may be effective for a broader range of blood cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR-T cells beyond CD19, UnCAR-Ted territory. Leick, MB., Maus, MV.[2020]

CAR T-cell therapy has shown remarkable success in treating B-cell acute lymphoblastic leukemia by targeting the CD19 marker, which is present on most B-cell tumors.

The therapy is being explored for other B-cell malignancies, including chronic lymphocytic leukemia and various types of lymphoma, although challenges remain in its application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? Pegram, HJ., Smith, EL., Rafiq, S., et al.[2018]

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 has shown significant promise in treating relapsed or refractory B-cell malignancies, such as B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia, by targeting specific antigens like CD19 and BCMA.

The review highlights both the efficacy and toxicity of CD19- and BCMA-targeted CAR-T-cell therapies, indicating that while these treatments can be effective, they also come with potential side effects that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data. Roex, G., Feys, T., Beguin, Y., et al.[2020]

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 1 clinical trial involving 14 patients with relapsed/refractory acute lymphoblastic leukemia (ALL) and non-Hodgkin lymphoma (NHL), the novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy demonstrated a strong safety profile, with no serious adverse events directly linked to the treatment and only mild cytokine release syndrome observed.

Efficacy results showed that 38% of patients with ALL achieved complete remission or incomplete count recovery, and 50% of patients with diffuse large B-cell lymphoma (DLBCL) also achieved complete remission, indicating promising antitumor activity of the SB-based CAR constructs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. Singh, H., Srour, SA., Milton, DR., et al.[2023]

CAR-T cell therapy has shown great promise in treating hematological cancers, with two Anti-CD19 CAR-T therapies already approved for CD19-positive leukemia and lymphoma.

However, the therapy can cause serious side effects like cytokine release syndrome and on-target off-tumor toxicity, leading to some patients discontinuing treatment; researchers are exploring various safety strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. Yu, S., Yi, M., Qin, S., et al.[2020]

CD19/20/22 CAR T-cells have been developed to effectively target B-lineage acute lymphoblastic leukemia (BL-ALL) that has relapsed with CD19(-) disease, showing efficacy in both laboratory and animal models.

These CAR T-cells maintain their effectiveness against CD19(+) disease while also being able to kill CD19(-) blasts, suggesting they could serve as a new treatment option for patients who do not respond to traditional CD19-targeting therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T-cells that target acute B-lineage leukemia irrespective of CD19 expression. Fousek, K., Watanabe, J., Joseph, SK., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7596761/

Optimized tandem CD19/CD20 CAR-engineered T cells in ... T cells engineered with a CD19-targeting CAR exhibit remarkable efficacy in patients with hematological malignancies, such as B-cell acute lymphocytic leukemia ...

2. nature.com nature.com/articles/s41375-021-01345-8

Long-term activity of tandem CD19/CD20 CAR therapy in ... Increasing the remission rate and reducing the recurrence rate can improve the clinical efficacy of chimeric antigen receptor (CAR) T cell ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04007029

NCT04007029 | Modified Immune Cells (CD19/CD20 CAR ... Combining CD19/CD20 CAR-T cells and chemotherapy may help treat patients with recurrent or refractory B-cell lymphoma or chronic lymphocytic leukemia. Detailed ...

4. ashpublications.org ashpublications.org/ashclinicalnews/news/5412/Tandem-CD19-CD20-CAR-T-Cells-Produce-Durable

Tandem CD19/CD20 CAR T Cells Produce Durable Antitumor ... Tandem CD19/CD20 CAR T Cells Produce Durable Antitumor Response in Relapsed/Refractory Non-Hodgkin Lymphoma Available · overall response: 79% ...

5. nature.com nature.com/articles/s41392-025-02269-w

CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05418088

NCT05418088 | Genetically Engineered Cells (Anti-CD19 ... This phase I trial tests the safety, side effects and best infusion dose of genetically engineered cells called anti-CD19/CD20/CD22 chimeric antigen receptor ( ...

7. ascopubs.org ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3034

Safety and efficacy of optimized tandem CD19/CD20 CAR ... Safety and efficacy of optimized tandem CD19/CD20 CAR-engineered T cells in patients with relapsed/refractory non-Hodgkin lymphoma. Author: ...