CAR-T Cells for Lymphoma

Overseen By Medical College of Wisconsin Cancer Center Clinical Trials Office

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Medical College of Wisconsin

Must be taking: BTK inhibitors

Must not be taking: Antidepressants, Chemotherapy, Steroids, others

Disqualifiers: HIV, Hepatitis B/C, Autoimmune, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 days

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called CAR-T cell therapy (specifically CAR-20/19-T Cells) for individuals with certain blood cancers, such as B-cell non-Hodgkin lymphoma and chronic lymphocytic leukemia, that haven't responded to other treatments. Researchers aim to determine the safety and effectiveness of this treatment. The trial includes different groups to evaluate the treatment under various conditions and identify the best usage method. Suitable participants have already tried other cancer treatments without success and have a type of blood cancer that impacts their daily life. As a Phase 1/Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group, offering participants a chance to be among the first to benefit from this innovative 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, certain treatments like anti-CD20 and anti-CD19 antibodies, as well as some chemotherapies, must be stopped a few weeks before the CAR-T cell infusion. It's best to discuss your specific medications with the trial team.

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

Research has shown that CAR-20/19-T cells have a good safety record. In one study, 94% of patients experienced cytokine release syndrome, a common side effect of cell therapies, but it was manageable. Brain-related side effects occurred in 18% of patients. Although these side effects are taken seriously, they are typical for this kind of treatment.

The treatment remains under investigation in early clinical trials, with researchers closely monitoring safety and side effects. Despite some risks, the potential benefits for treating difficult cases of lymphoma make it worth exploring. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAR-20/19-T cell therapy because it offers a novel approach for treating lymphomas, including non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL), and mantle cell lymphoma (MCL). Unlike traditional treatments like chemotherapy and radiation, which target cancer cells indirectly, CAR-T cells are engineered to specifically recognize and attack cancer cells. This personalized approach uses a patient's own immune cells, reprogramming them to better fight cancer. Additionally, the 8/12-day production process for these CAR-T cells could streamline manufacturing, making the treatment more accessible and potentially faster than current options.

What evidence suggests that this trial's treatments could be effective for B cell malignancies?

Research has shown that CAR-20/19-T cell therapy holds great promise for treating various types of lymphoma and leukemia. In this trial, participants will receive CAR-20/19-T cells, which demonstrated significant effectiveness in previous studies. Specifically, for patients with non-Hodgkin lymphoma (NHL), 90% saw their cancer shrink or disappear. For those with chronic lymphocytic leukemia (CLL), similar CAR-T cells resulted in an 82% response rate, with many patients experiencing complete remission. In mantle cell lymphoma (MCL), the response rate reached an impressive 100%, with 88% of patients achieving complete remission. Additionally, evidence suggests that CAR-T cells targeting CD19 or CD20 are effective for central nervous system (CNS) lymphomas. These findings indicate that CAR-T cells could be a powerful treatment option for these challenging cancers. ^{1 2 6 7 8}

Who Is on the Research Team?

Nirav Shah, MD

Principal Investigator

Medical College of Wisconsin

Are You a Good Fit for This Trial?

Adults aged 18-80 with various types of B-cell non-Hodgkin Lymphoma that have not responded to previous treatments. Participants must be in good general health, with a performance score indicating they can care for themselves and perform light work, and no active infections like HIV or Hepatitis B/C. They cannot have had certain recent cancer treatments or organ transplants, and women must not be pregnant.

Inclusion Criteria

My cancer can be measured by scans or has affected my bone marrow.

My kidney function is good, with creatinine clearance over 60 ml/min and serum Cr at or below 1.5 mg/dL.

Agree to practice birth control during the study

Exclusion Criteria

I have severe side effects from past treatments not caused by my disease.

Positive beta-HCG in female of childbearing potential

I have previously received CAR T-cell therapy from a donor.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive CAR-20/19-T cells with IL-7/IL-15 expansion to evaluate safety and efficacy

8-12 days

Multiple visits for cell infusion and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Regular visits for monitoring adverse events

Phase 2 Evaluation

Determine the 3-month complete response rate of CAR-20/19-T cells in MCL

3 months

What Are the Treatments Tested in This Trial?

Interventions

• CAR-20/19-T Cells

Trial Overview The trial is testing CAR-20/19-T cells made using Interleukin-7 and Interleukin-15 in patients with relapsed or refractory B cell malignancies. It's an early-phase study assessing the safety, effectiveness, and feasibility of producing these cells over different time frames (8/12 days) including cryopreserved options.

How Is the Trial Designed?

Group I: Phase 2 - Efficacy of CAR-20/19-T cells in MCL Experimental Treatment 1 Intervention

Single-stage Phase II design with three-month CR as the target endpoint.

Group II: 8/12 Flexible Manufacturing with Mandated Cryopreservation Experimental Treatment 1 Intervention

8/12 flexible manufacturing with mandated cryopreservation prior to infusion of LV20.19 CAR T-cells. The enrollment will cap at 24 subjects.

Group III: 8/12 Day Production of CAR-T for Relapsed/Refractory Primary or Secondary CNS Lymphoma Experimental Treatment 1 Intervention

Phase 1: Determine safety of 2.5x106 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with primary/secondary central nervous system (CNS) lymphoma. Phase 1b: Safety and efficacy will be evaluated in this study that will enroll 12 to 24 patients.

Group IV: 8/12 Day Production of CAR-T for NHL Experimental Treatment 1 Intervention

Phase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with relapsed, refractory B-cell NHL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts at eight or 12-day manufacturing. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 in each group.

Group V: 8/12 Day Production of CAR-T for CLL Experimental Treatment 1 Intervention

Phase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with CLL. Patients will be enrolled in 3+3 fashion. Phase 1b: The enrollment will cap at 24 subjects.

Group VI: 12-Day Production of Car-T Cells for NHL Experimental Treatment 1 Intervention

Phase 1: Determine safety of 2.5x10\^6 cells/kg IL-7/IL-15 expanded CAR-20/19-T cells in patients with relapsed, refractory B-cell NHL. Patients will be enrolled in 3+3 fashion. Phase 1b: Six to nine patient expansion cohorts at 12-day manufacturing. If six patients are enrolled in Phase 1 then only six additional patients will be added. If three patients are enrolled in Phase 1 then nine additional patients will be treated for a total of 12 in each group.

Who Is Running the Clinical Trial?

Medical College of Wisconsin

Lead Sponsor

Trials

645

Recruited

1,180,000+

Published Research Related to This Trial

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]

In a phase IIa trial involving 11 patients with relapsed or refractory CD20+ B-cell lymphoma, the use of CAR-modified T cells (CART-20) resulted in an impressive overall response rate of 81.8%, with 6 complete remissions and 3 partial remissions, indicating strong efficacy.

The treatment was well-tolerated with no severe toxicity reported, and the median progression-free survival was over 6 months, suggesting that CART-20 is a promising option for patients with difficult-to-treat lymphomas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of CD20-directed Chimeric Antigen Receptor-modified T cells in patients with relapsed or refractory B-cell non-Hodgkin lymphoma: an early phase IIa trial report. Zhang, WY., Wang, Y., Guo, YL., et al.[2021]

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]

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]

CD19-directed CAR-T therapy has shown promising long-term results, achieving durable remissions in nearly 50% of patients with relapsed/refractory large B-cell lymphoma, significantly improving their prognosis compared to the previous median survival of about 6 months with standard treatments.

The success of CAR-T therapy in large B-cell lymphoma has led to its expansion into other types of lymphomas, such as mantle cell and follicular lymphoma, and ongoing development of new CAR-T platforms aimed at enhancing efficacy and reducing toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Indications and platforms for CAR-T therapy in lymphomas beyond DLBCL. Iqbal, M., Savani, BN., Hamadani, M.[2023]

In a phase I study involving 10 patients with refractory diffuse large B-cell lymphoma (DLBCL), the anti-CD19 CAR T cell therapy (C-CAR011) demonstrated a 50% overall response rate at 12 weeks, indicating promising efficacy for this treatment.

The therapy showed a favorable safety profile, with 90% of patients experiencing cytokine release syndrome but no severe (grade ⩾ 3) cases or neurotoxicity, suggesting it is a safe option for patients with heavily treated DLBCL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase I study of CBM.CD19 chimeric antigen receptor T cell in the treatment of refractory diffuse large B-cell lymphoma in Chinese patients. Fan, L., Wang, L., Cao, L., et al.[2022]

CAR T-cell therapy, particularly anti-CD19 CAR T cells, shows strong efficacy in treating resistant forms of B-cell lymphomas, achieving durable complete remissions lasting over 2 years in some patients with refractory diffuse large-B-cell lymphoma (DLBCL).

Despite their effectiveness, CAR T-cell therapies can lead to severe toxicities, such as cytokine-release syndrome and neurological issues, highlighting the need for careful management and ongoing research into safer CAR designs and treatment combinations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. Brudno, JN., Kochenderfer, JN.[2022]

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]

CAR19-engineered invariant natural killer T (iNKT) cells show enhanced anti-lymphoma activity compared to traditional CAR19-T cells, leading to improved tumor-free and overall survival in both laboratory and animal studies.

The combination of CAR19-iNKT cells with all-trans retinoic acid further boosts their effectiveness against CD19+ chronic lymphocytic leukemia, suggesting a promising new approach for treating lymphomas and potentially other cancers that express CD1d.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. Rotolo, A., Caputo, VS., Holubova, M., et al.[2021]

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]

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-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]

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]

CD19CAR T cells have shown promising results in treating aggressive B-lineage cancers, but their effectiveness can be limited by the loss of the targeted CD19 antigen, leading to treatment failure.

The newly developed adapter CAR T cell technology (AdCAR) allows for multitargeting of different antigens, such as CD20 and CD22, which can enhance the anti-cancer activity and potentially overcome issues related to antigen loss in lymphoma treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. Atar, D., Mast, AS., Scheuermann, S., et al.[2022]

In a study involving 9 patients with refractory/relapsed B cell lymphoma, a novel anti-CD19 CAR T cell therapy showed a high overall response rate of 77.8%, with 55.6% achieving complete remission.

The treatment demonstrated a favorable safety profile, with only 11.1% of patients experiencing severe cytokine release syndrome and neurotoxicity, while some patients maintained complete remission for over 20 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel dominant-negative PD-1 armored anti-CD19 CAR T cell is safe and effective against refractory/relapsed B cell lymphoma. Liu, X., Zhang, Y., Li, K., et al.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666636721012975

Driving Out Chronic Lymphocytic Leukemia With CAR T Cells In this comprehensive review we explore novel targets for CAR T cell therapy in CLL and highlight the promising results of CAR T cell trials reported to date.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04186520

Study Details | NCT04186520 | CAR-20/19-T Cells in ... This is a Phase I/II, interventional, single-arm, open-label, treatment study designed to evaluate the safety and efficacy of Interleukin-7 and Interleukin-15 ...

3. nature.com nature.com/articles/s41408-024-01105-8

Bispecific CAR-T cells targeting CD19/20 in patients with ... The overall response rate (ORR) to second-line therapy is reported to be 20%–30% with a median overall survival (OS) of 6 months in patients who ...

4. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33020647/

Bispecific anti-CD20, anti-CD19 CAR T cells for relapsed B ... Eighteen (82%) patients achieved an overall response at day 28, 14 (64%) had a complete response, and 4 (18%) had a partial response. The ...

5. astctjournal.org astctjournal.org/article/S2666-6367(21)01297-5/pdf

Driving Out Chronic Lymphocytic Leukemia With CAR T Cells Anti-CD19 CAR T cell therapy is showing promising efficacy for CLL in clinical trials, even in high-risk and R/R cases [30 33]. One advantage of ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9772271/

Serious adverse events and coping strategies of CAR-T cells ... Numerous clinical studies have shown that CAR-T cells can cause SAEs in the treatment of both hematological and solid tumors ( Figure 1 ). The SAEs can affect ...

7. onclive.com onclive.com/view/lv20-19-car-t-cell-therapy-yields-100-orr-in-r-r-mantle-cell-lymphoma

LV20.19 CAR T-Cell Therapy Yields 100% ORR in R ... The treatment exhibited a favorable safety profile, with cytokine release syndrome in 94% of patients and neurotoxicity in 18%.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10064560/

CAR T-Cell therapy for the management of mantle cell ... The treatment involves taking T-cells from an infected person and altering the cells genetically to identify and destroy lymphoma cells [31].