CAR T-Cell Therapy for Blood Cancer

(CARPASCIO Trial)

Not currently recruiting at 1 trial location

Overseen By Carlos Ramos, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Must not be taking: Corticosteroids

Disqualifiers: Severe infection, GVHD, Pregnancy, others

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

Compensation: Varies

Number of Visits: 1

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment that combines the body's antibodies and T cells (a type of immune cell) to combat blood cancers like leukemia and lymphoma. Researchers create special T cells, called CAR T-cells (CD19.CAR-CD28Z T Cells), designed to better target and destroy cancer cells. The trial aims to find the safest dose, understand side effects, and determine if this approach can help patients whose cancer has returned or not responded to other treatments. It seeks participants with specific forms of leukemia or lymphoma who have had a stem cell transplant and still show cancer signs. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications, but you cannot be on other investigational antitumor therapy for one month before joining the study. Also, you cannot be taking high doses of corticosteroids for GVHD treatment.

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

Research shows that CD19/CAR-T cell therapy, such as the CD19.CAR-CD28Z T cells used in this trial, is generally well-tolerated by people with blood cancers. In past studies, these treatments proved very successful, with some patients seeing their cancer completely disappear. However, some known side effects exist.

For example, some patients experienced cytokine release syndrome (CRS), which can cause fever and flu-like symptoms due to the body's immune response to the therapy. The risk of CRS increases when there is a high cancer burden. Fortunately, doctors have found effective ways to manage this side effect.

Additionally, CD19/CAR-T cell treatment uses modified T cells, which are part of the immune system. These T cells are specially designed to better target cancer cells. While they have shown promise, researchers are still learning the best ways to use them safely.

Overall, despite potential side effects, researchers continue to find ways to reduce risks and improve outcomes for patients. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CAR T-Cell Therapy, specifically the CD19.CAR-CD28Z T Cells, because it offers a cutting-edge approach to treating blood cancers like B-cell ALL and other B-cell malignancies. Unlike traditional treatments such as chemotherapy and radiation, which attack cancer cells and healthy cells indiscriminately, CAR T-Cell Therapy involves modifying a patient's own T-cells to specifically target and destroy cancer cells. This precision reduces harm to healthy cells and can lead to more effective and lasting remissions. Additionally, this therapy can be tailored to patients with either HLA-matched or mismatched donors, making it versatile and accessible to a broader range of patients.

What evidence suggests that CD19.CAR-CD28Z T Cells might be an effective treatment for lymphoma or leukemia?

Research has shown that CD19 CAR T-cell therapy holds promise for treating blood cancers such as lymphoma and leukemia. In one study, 88% of patients experienced a complete response to treatment with 19-28z CD19 CAR T cells. Another study found the therapy to be about 75% effective. This trial will evaluate CD19.CAR-CD28Z T Cells in different patient subgroups, with variations in donor matching and dose escalation. This treatment uses special immune cells called T cells, which are modified to better locate and attack cancer cells. The CD19 antibody enhances the ability of these T cells to find cancer cells. Although the FDA has not yet approved this treatment, early results suggest it could be very effective against certain blood cancers. ^{1 2 3 6 7}

Who Is on the Research Team?

Carlos Ramos, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for patients with certain blood cancers (NHL, ALL, CLL) that have returned or persisted despite treatment. Participants must be undergoing or have undergone a stem cell transplant and have an identified donor. They should not be on other investigational antitumor therapies, must meet specific health criteria like organ function, and agree to effective birth control use.

Inclusion Criteria

Life expectancy of ≥12 weeks

Bilirubin ≤ 2 times the upper limit of normal

Patients or legal guardians must sign an informed consent

Exclusion Criteria

Pregnant or lactating

History of hypersensitivity reactions to murine protein-containing products

My graft-versus-host disease is more severe than grade II.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-treatment

Participants may receive chemotherapy with cyclophosphamide and fludarabine if their circulating T cell levels are high

1-2 weeks

Treatment

Participants receive an injection of CD19/CD28 chimeric receptor-T cells and are monitored for up to 4 hours post-infusion

6 weeks

1 visit (in-person) for infusion, followed by monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, with potential for additional T cell infusions if beneficial

4-6 weeks

Regular follow-up visits (in-person)

Long-term follow-up

Participants are followed for long-term side effects of gene transfer

Up to 15 years

What Are the Treatments Tested in This Trial?

Interventions

• CD19.CAR-CD28Z T Cells

Trial Overview The study tests the safety and effectiveness of CD19.CAR-CD28Z T Cells at escalating doses in fighting lymphoma/leukemia post-stem cell transplantation from a donor. It aims to determine the maximum safe dose, how long these modified T cells last in the body, side effects they may cause, and their potential benefits.

How Is the Trial Designed?

Group I: Subgroup B2 Experimental Treatment 1 Intervention

Patients with other B cell malignancies and with an unrelated or HLA-mismatched donor will receive CD19.CAR-CD28Z T Cells - dose escalation 2

Group II: Subgroup B1 Experimental Treatment 1 Intervention

Patients with other B-cell malignancies and with an HLA-matched related donor will receive CD19.CAR-CD28Z T Cells - dose escalation 1

Group III: Subgroup A2 Experimental Treatment 1 Intervention

Patients with residual or relapsed B-cell ALL and with an unrelated or HLA-mismatched donor will receive CD19.CAR-CD28Z T Cells - dose escalation 2

Group IV: Subgroup A1 Experimental Treatment 1 Intervention

Patients with residual or relapsed B-cell ALL and with an HLA-matched related donor will receive CD19.CAR-CD28Z T Cells - dose escalation 1

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

In a review of 60 studies involving 913 participants, CAR-T cell therapy showed a promising complete response rate of 54.4% in patients with CD19+ hematologic malignancies, indicating its efficacy in treating certain blood cancers.

However, safety concerns were significant, with 55.3% of hematologic patients experiencing cytokine release syndrome and 37.2% experiencing neurotoxicity, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis. Grigor, EJM., Fergusson, D., Kekre, N., et al.[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]

CD19 is a highly effective target for CAR T-cell therapies, showing significant responses in patients with relapsed B-cell malignancies, particularly chronic lymphocytic leukemia and acute lymphoblastic leukemia.

While treatment with CD19-CAR T cells can lead to severe systemic inflammatory reactions, these are generally reversible with proper medical care, highlighting the importance of monitoring during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR trials. Ramos, CA., Savoldo, B., Dotti, G.[2022]

Chimeric antigen receptor (CAR) and T cell receptor (TCR) engineered T cells show promise in treating blood cancers, particularly with CD19-CAR-T cells demonstrating strong clinical responses in B-cell malignancies.

To enhance the effectiveness and safety of these therapies, researchers are exploring new antigens, improved T cell culture methods, and better administration protocols to address issues like treatment failure and toxicities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Overcoming key challenges in cancer immunotherapy with engineered T cells. Arcangeli, S., Mestermann, K., Weber, J., et al.[2021]

CD19+ CAR T-cells have shown high effectiveness against various cancers, but their complete risk profile, including complications, was not fully understood during initial clinical trials.

Emerging evidence from post-approval studies reveals significant complications associated with CD19+ CAR T-cell therapy, such as cytokine release syndrome and neurotoxicity, indicating that these therapies can affect multiple organ systems and may lead to long-term health issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications after CD19+ CAR T-Cell Therapy. Penack, O., Koenecke, C.[2020]

CD19-targeted CAR T cell therapy has shown remarkable efficacy, achieving complete remission in 70-90% of patients with relapsed/refractory acute lymphoblastic leukemia (ALL), highlighting its potential as a powerful treatment for B cell malignancies.

The ongoing phase I study using a non-viral gene transfer method (piggyBac-transposon system) for CD19 CAR T cell therapy in pediatric and young adult patients indicates a promising direction for expanding treatment options in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gene-modified T-cell therapy using chimeric antigen receptors for pediatric hematologic malignancies. Nakazawa, Y.[2017]

In a study involving 9 patients with relapsed or refractory B cell non-Hodgkin's lymphoma, both CD28 and 4-1BB targeted CAR-T cells showed similar antitumor efficacy, achieving a complete response rate of 67% within 3 months.

However, the 4-1BB (BBz CAR-T) cells were better tolerated, with only mild adverse events, while the CD28 (28z CAR-T) cells caused severe side effects, leading to the discontinuation of further evaluation for that group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Parallel Comparison of 4-1BB or CD28 Co-stimulated CD19-Targeted CAR-T Cells for B Cell Non-Hodgkin's Lymphoma. Ying, Z., He, T., Wang, X., et al.[2020]

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]

In a study involving five adults with relapsed B cell acute lymphoblastic leukemia (B-ALL), treatment with autologous T cells modified to express a CD19-specific CAR (19-28z) led to rapid tumor eradication and complete remissions without minimal residual disease (MRD), indicating strong efficacy of this therapy.

The treatment was generally well tolerated, although patients with higher tumor burdens experienced significant cytokine elevations, which required management with steroids, highlighting the need for monitoring and potential intervention during therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Brentjens, RJ., Davila, ML., Riviere, I., et al.[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]

CD19-specific CAR T cell therapies are effective for treating difficult-to-treat blood cancers, but they can cause significant cardiovascular toxicity, including issues like tachycardia, arrhythmias, and left ventricular dysfunction.

There is a need for more research to better understand these cardiovascular risks and to develop a cardiac surveillance protocol for patients undergoing CAR T cell therapy, ensuring safer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T Cell Therapy-Related Cardiovascular Outcomes and Management: Systemic Disease or Direct Cardiotoxicity? Ghosh, AK., Chen, DH., Guha, A., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4684949/

Efficacy and Toxicity Management of 19-28z CAR T Cell ... In contrast, patients treated with 19-28z CD19 CAR T cells had a very high overall complete response rate (88%), with 86% of the patients from this CR group ...

2. bmccancer.biomedcentral.com bmccancer.biomedcentral.com/articles/10.1186/s12885-024-12651-6

CD19 CAR T cells for B cell malignancies: a systematic review ... The overall BCR rate was 56%, with 60% OS and 75% BOR. Younger patients displayed remarkably higher BCR prevalence without differences in OS.

3. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5877/527643/Long-Term-Outcomes-and-Adverse-Events-of-CAR-T-19

Long-Term Outcomes and Adverse Events of CAR T-19 Cell ... Anti-CD19 CAR T-cell therapy showed the highest efficacy with an event rate of 74.75% (95% CI: 61% to 80%, I² = 89.84%). Combination therapies ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497124025461

The present and future of CAR T-cell therapy for adult B- ... Long-term remission rates are inversely correlated with age (30%-40% in adults; >90% in children), and relapsed/refractory (R/R) disease in ...

5. cell.com cell.com/molecular-therapy-family/oncology/fulltext/S2372-7705(20)30095-4

Efficacy and Safety of CD28- or 4-1BB-Based CD19 CAR-T ... Our pre-clinical and clinical results consistently demonstrate that 4-1BB CAR-T cells are more effective in suppressing B-ALL than CD28 CAR-T ...

6. ascopubs.org ascopubs.org/doi/10.1200/jco.2015.33.15_suppl.7010

Efficacy and safety of CD19-targeted 19-28z CAR modified ... 19-28z CAR T cells can induce a high CR rate of 91% in adult patients with R/R ALL. The risk of sCRS correlates with disease burden and can be effectively ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S2666636723014203

Clinical Variables Associated with Improved Outcomes for ... Here we review published CAR-T trials and consortium/collaborative outcomes to establish variables associated with optimal response to CAR-T in children and ...