CAR-T Cells for Lymphoma

Recruiting in Palo Alto (17 mi)

Overseen by Nirav Shah, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1 & 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

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 (IL-7/IL-15) manufactured chimeric antigen receptor (CAR)-20/19-T cells as well as the feasibility of a flexible manufacturing schema in adult patients with B cell malignancies that have failed prior therapies.

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.

What data supports the effectiveness of the treatment CAR-20/19-T Cells for Lymphoma?

Research shows that CAR-T cell therapy, which includes targeting CD19 and CD20, has been effective in treating aggressive B-cell lymphomas, with studies reporting high response rates and some patients achieving complete remission. This suggests that CAR-20/19-T Cells could be promising for treating lymphoma, as similar therapies have shown success in related conditions. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapy, including versions targeting CD19, has been associated with some risks, such as cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage), but these are generally manageable. Studies have shown that while all patients may experience some adverse effects, severe cases are less common, and the therapy is considered safe for treating certain types of lymphoma. ^{6 7 8 9 10}

How is the CAR-20/19-T Cells treatment different from other treatments for lymphoma?

The CAR-20/19-T Cells treatment is unique because it targets two antigens, CD19 and CD20, on cancer cells, which may help prevent the cancer from escaping treatment by losing one of these targets. This dual-targeting approach is different from traditional CAR T-cell therapies that typically focus on a single antigen, potentially increasing the effectiveness against lymphoma. ^{11 12 13 14 15}

Research Team

Nirav Shah, MD

Principal Investigator

Medical College of Wisconsin

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• CAR-20/19-T Cells (CAR T-cell Therapy)

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.

Participant Groups

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+

Dr. Joseph E. Kerschner

Medical College of Wisconsin

Chief Medical Officer since 2011

MD, specific institution not identified

Dr. John R. Raymond, Sr.

Medical College of Wisconsin

Chief Executive Officer since 2010

MD from the Medical University of South Carolina

Findings from Research

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

References

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

Chimeric Antigen Receptor T-Cell Therapy in Aggressive B-Cell Lymphoma. [2023]

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

New Indications and platforms for CAR-T therapy in lymphomas beyond DLBCL. [2023]

3. England 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. [2021]

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

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

5. 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]

6. United States 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. [2021]

7. China 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. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T-cell therapies for lymphoma. [2022]

9. 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]

10. Denmark pubmed.ncbi.nlm.nih.gov

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

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

Cellular therapy in lymphoma. [2023]

12. Switzerland pubmed.ncbi.nlm.nih.gov

Adapter CAR T Cell Therapy for the Treatment of B-Lineage Lymphomas. [2022]

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

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

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

Enhanced Anti-lymphoma Activity of CAR19-iNKT Cells Underpinned by Dual CD19 and CD1d Targeting. [2021]

15. Netherlands pubmed.ncbi.nlm.nih.gov

T-cells fighting B-cell lymphoproliferative malignancies: the emerging field of CD19 CAR T-cell therapy. [2017]