CAR-T Cell Therapy for Lymphoma and Leukemia

Overseen By Clinical Trials Referral Office

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Mayo Clinic

Must not be taking: Systemic corticosteroids

Disqualifiers: Pregnancy, Seizure disorder, HIV, others

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

Compensation: Varies

Number of Visits: 60

Duration: 1 day

25 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase I trial studies the effects of CD-19 directed chimeric antigen receptor (CAR)-T cell therapy for the treatment of patients with B cell malignancies that have come back (recurrent) or have not responded to treatment (refractory). CD-19 CAR-T cells use some of a patient's own immune cells, called T cells, to kill cancer. T cells fight infections and, in some cases, can also kill cancer cells. Some T cells are removed from the blood, and then laboratory, researchers will put a new gene into the T cells. This gene allows the T cells to recognize and possibly treat cancer. The new modified T cells are called the IC19/1563 treatment. IC19/1563 may help treat patients with relapsed/refractory B cell malignancies.

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) that must be met before a procedure called leukapheresis, which is part of the trial.

What data supports the effectiveness of the treatment IC19/1563 for lymphoma and leukemia?

CAR-T cell therapy targeting CD19 has shown remarkable results, achieving complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia, compared to a 30% response rate with chemotherapy. This success has led to its expansion in treating other types of lymphoma, with durable remissions in nearly half of the patients with large B-cell lymphoma. ^{1 2 3 4 5}

Is CAR-T cell therapy safe for humans?

CAR-T cell therapy has shown a generally good safety profile in clinical trials for conditions like leukemia and lymphoma. Some patients experienced mild to moderate side effects like cytokine release syndrome (a reaction that can cause fever and low blood pressure) and neurotoxicity (effects on the nervous system), but serious adverse events were rare. ^{6 7 8 9 10}

How is the treatment IC19/1563 different from other treatments for lymphoma and leukemia?

IC19/1563 is a CAR-T cell therapy, which is a type of immunotherapy that uses genetically modified T cells to target and destroy cancer cells. This treatment is unique because it specifically targets the CD19 protein found on the surface of B-cell cancers, offering a potentially curative option for patients with relapsed or refractory lymphoma and leukemia who have limited treatment options. ^{1 11 12 13 14}

Research Team

Saad Kenderian, MB, ChB

Principal Investigator

Mayo Clinic in Rochester

Eligibility Criteria

Adults with certain types of B cell malignancies that have not responded to or have returned after treatment. They must have had multiple prior therapies, be in good physical condition, and meet specific blood count and organ function criteria. Pregnant or breastfeeding individuals are excluded, as well as those who can get approved CD19 CAR T-cell therapies elsewhere.

Inclusion Criteria

Willingness to provide mandatory blood specimens for correlative research

Willing to return to enrolling institution for follow-up (during the Active Monitoring Phase of the study)

You have a certain type of leukemia called SLL or CLL and have previously received at least two lines of therapy, or have been taking a medication called ibrutinib for at least 6 months. You must also have measurable disease, certain blood counts, and normal liver and kidney function. Additionally, you must not have any major heart or lung problems, must not be pregnant or planning to become pregnant, and must be willing to provide blood samples for research and follow-up visits to the study site.

Exclusion Criteria

I am not on any cancer treatments, except for certain allowed ones.

I have had a heart attack.

I had a stem cell transplant more than 100 days ago, with no ongoing GVHD or immunosuppression.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment Conditioning

Patients receive cyclophosphamide and fludarabine or bendamustine as conditioning therapy before CAR-T cell infusion

3-5 days

In-patient stay for conditioning therapy

Treatment

Patients receive IC19/1563 CAR-T cell infusion

1 day

In-patient stay for CAR-T cell infusion

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and response evaluation

Up to 15.5 years

Follow-up visits on days 60, every 3 months up to year 3, every 6 months from years 3-5, and then annually

Treatment Details

Interventions

• IC19/1563

Trial Overview The trial is testing a new therapy where patients' own immune cells (T cells) are modified in the lab to target cancer more effectively. This involves adding a gene so these T cells can recognize and potentially kill cancerous B cells using the IC19/1563 treatment.

Participant Groups

Group I: Treatment (cyclophosphamide, fludarabine, IC19/1563) Experimental Treatment 10 Interventions

Patients receive cyclophosphamide IV over 60 minutes and fludarabine IV over 30 minutes on days -5, -4, -3, or bendamustine IV over 10 minutes on days -4 and -3, and IC19/1563 IV on day 0. Patients also undergo bone marrow biopsy and aspiration, CT-PET or CT scans, MRI, and collection of blood and tissue samples throughout the trial.

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Findings from Research

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]

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]

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]

Chimeric antigen receptor (CAR) T-cell therapy has shown effectiveness in treating B-cell leukemia and lymphoma, but there is a significant risk of relapse due to loss of targeted antigens or the CAR T-cells' intrinsic failures.

To improve long-term control of leukemia and lymphoma, researchers are exploring advanced strategies such as targeting multiple antigens simultaneously and combining CAR T-cell therapy with checkpoint inhibitors, which are currently in early clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Engineering T-cells with chimeric antigen receptors to combat hematological cancers: an update on clinical trials. Ormhøj, M., Abken, H., Hadrup, SR.[2022]

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 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]

A new assay for detecting CAR-T19 cells showed high accuracy and reproducibility, allowing for effective monitoring of these cells in blood and cerebrospinal fluid (CSF) from patients, even in those with low blood cell counts.

This assay can differentiate CAR-T19 cells from reactive T-cells in cases of suspected neurotoxicity, and it can be adapted to study the memory and exhaustion status of both CAR-T19 and native T-cells, making it a versatile tool for patient management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of CAR-T19 cells in peripheral blood and cerebrospinal fluid: An assay applicable to routine diagnostic laboratories. Johansson, U., Gallagher, K., Burgoyne, V., et al.[2022]

In a review of phase I clinical trials involving 29 patients with B-lineage malignancies, anti-CD19 CAR T-cell therapy demonstrated a 6-month progression-free survival rate of 50%, indicating its potential efficacy in treating these cancers.

The study found that preconditioning with lymphodepletion and the use of interleukin-2 (IL-2) improved patient outcomes, while the most common treatment-related side effects included fever and acute renal failure, suggesting that while the therapy is generally well tolerated, monitoring for adverse effects is important.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials. Xu, XJ., Zhao, HZ., Tang, YM.[2019]

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]

Dual-targeting CAR-T cell therapy shows promising efficacy in treating B cell malignancies, with a 77% overall response rate and 52% complete response rate in patients with B cell non-Hodgkin lymphoma (B-NHL), and a 92% complete response rate in patients with B cell acute lymphoblastic leukemia (B-ALL).

The therapy has a manageable safety profile, with grade ≥3 cytokine release syndrome occurring in 14% of B-NHL patients and 11% of B-ALL patients, indicating that while there are risks, the benefits may outweigh them for many patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis. Yu, M., Zhang, Q., Kong, F., et al.[2023]

CAR-T therapy has shown promising results in treating leukemia and lymphoma, offering potentially curative options for patients who previously had limited treatment choices, as highlighted in studies presented at the 61st annual meeting of the American Society of Hematology.

Recent advancements in CAR-T constructs aim to enhance treatment efficacy and durability while also improving strategies to manage toxicity, indicating a focus on both effectiveness and patient safety in the evolving field of cellular immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Updates in Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Lymphoma and Leukemia from the Annual Meeting of American Society of Hematology 2019. Bukhari, A., Siglin, J., Lutfi, F., 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]

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]

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

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

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

CAR-T cells beyond CD19, UnCAR-Ted territory. [2020]

3. Japan pubmed.ncbi.nlm.nih.gov

Biology and clinical application of CAR T cells for B cell malignancies. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Engineering T-cells with chimeric antigen receptors to combat hematological cancers: an update on clinical trials. [2022]

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

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

6. Switzerland pubmed.ncbi.nlm.nih.gov

Sleeping beauty generated CD19 CAR T-Cell therapy for advanced B-Cell hematological malignancies. [2023]

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

Detection of CAR-T19 cells in peripheral blood and cerebrospinal fluid: An assay applicable to routine diagnostic laboratories. [2022]

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

Efficacy and safety of adoptive immunotherapy using anti-CD19 chimeric antigen receptor transduced T-cells: a systematic review of phase I clinical trials. [2019]

9. England pubmed.ncbi.nlm.nih.gov

Next generation chimeric antigen receptor T cells: safety strategies to overcome toxicity. [2020]

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

Efficacy and Safety of Dual-Targeting Chimeric Antigen Receptor-T Therapy for Relapsed or Refractory B Cell Lymphoid Malignancies: A Systematic Review and Meta-Analysis. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Updates in Chimeric Antigen Receptor T-Cell (CAR-T) Therapy for Lymphoma and Leukemia from the Annual Meeting of American Society of Hematology 2019. [2020]

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

Review: Current clinical applications of chimeric antigen receptor (CAR) modified T cells. [2022]

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

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

14. Netherlands pubmed.ncbi.nlm.nih.gov

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