CAR T-Cell Therapy for Leukemia and Lymphoma

(SAGAN Trial)

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: Investigational agents, Tumor vaccines

Disqualifiers: Active infection, Other cancer, Pregnancy, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 6 weeks

64 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treating certain types of lymphoma and leukemia, specifically for those whose cancer has returned or hasn't responded to other treatments. It uses a special type of immune system cell called a T cell, modified in the lab to better target and fight cancer cells. This modification is known as CAR T-cell therapy. Some participants will receive T cells with an added boost from two proteins, while others will get T cells with just one protein, to determine which works best. The trial seeks individuals with a history of lymphoma or leukemia, particularly if their condition has persisted or returned after previous treatments. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does allow treatment with PD1/PDL1 inhibitors if medically indicated. It also excludes those currently receiving investigational agents or tumor vaccines within the previous 6 weeks.

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

Research has shown that CD19 CAR T-cell therapy holds promise for safety. Studies have found this treatment to be generally safe and well-tolerated in patients with certain types of leukemia and lymphoma. Reports and small trials suggest that CD19-directed CAR T-cell therapy effectively treats B-cell cancers that have returned or are unresponsive to other treatments.

Other clinical trials have demonstrated that CD19-specific CAR T-cell therapy is safe for patients with relapsed or hard-to-treat B-cell acute lymphoblastic leukemia (R/R B-ALL). While side effects can occur, as with any treatment, the overall safety results remain encouraging.

This therapy is still under study to fully understand its effects. However, the data so far indicates it is generally safe for the patients studied. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about CAR T-Cell therapy for leukemia and lymphoma because it represents a cutting-edge approach that harnesses the patient's own immune system to fight cancer. Unlike traditional treatments like chemotherapy and radiation, which can be non-specific and damage healthy cells, this therapy involves genetically engineering T cells to specifically target and destroy cancer cells. The CD19.CAR/28 and CD19.CAR/28137 T cells are designed to recognize and attack B-cell cancers more precisely, potentially leading to better outcomes with fewer side effects. This innovative mechanism of action offers hope for more effective and personalized cancer treatment.

What evidence suggests that this trial's treatments could be effective for lymphoma or leukemia?

Research has shown that CD19 CAR T-cell therapy holds promise for treating leukemia and lymphoma. In patients whose B-cell acute lymphoblastic leukemia (B-ALL) has returned or resisted treatment, this therapy led to complete remission in 70% to 90% of cases. Participants in this trial will receive CD19 CAR T-cell therapy, which uses specially designed T cells to locate and destroy cancer cells with the CD19 protein. Studies have also found CD19 CAR T cells effective in treating non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL), suggesting it could be a strong option for managing these challenging cancers. ^{6 7 8 9 10}

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 people up to 75 years old with certain types of blood cancers like B-cell lymphoma, ALL, or CLL that have come back or didn't respond to treatment. They should be fit enough for the study and not have infections needing antibiotics, HIV/HTLV, or a history of severe reactions to mouse proteins.

Inclusion Criteria

TREATMENT: Bilirubin less than 3 times the upper limit of normal.

TREATMENT: AST less than 5 times the upper limit of normal.

PROCUREMENT: Hgb greater than or equal to 7.0 (can be a transfused value).

Exclusion Criteria

TREATMENT: History of hypersensitivity reactions to murine protein-containing products.

I am currently on antibiotics for an active infection.

I have no cancer history, except for certain skin, breast, or cervix cancers treated over 2 years ago.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of CD19 CAR T Cells, with potential pre-treatment using cyclophosphamide and fludarabine if necessary

6 weeks

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

Evaluation

6-week evaluation period to assess treatment benefit, with potential for additional doses if beneficial

6 weeks

1 visit (in-person) for evaluation

Follow-up

Participants are monitored for safety and effectiveness after treatment, with long-term follow-up for gene transfer side effects

15 years

What Are the Treatments Tested in This Trial?

Interventions

• CD19.CAR/28 and CD19.CAR/28137 T cells
• Cyclophosphamide
• Fludarabine

Trial Overview The trial tests two modified T-cell therapies against aggressive blood cancers. One therapy includes CD19.CAR/28 T cells; the other adds CD137 to enhance effectiveness. The goal is to find the safest high dose, understand side effects, and see if these therapies can help patients.

How Is the Trial Designed?

Group I: Dose Expansion: CD19 CAR T Cells for B-cell NHL/CLL Experimental Treatment 1 Intervention

Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

Group II: Dose Expansion: CD19 CAR T Cells for B-cell ALL Experimental Treatment 1 Intervention

Each patient will receive the maximum tolerated dose (MTD) of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

Group III: Dose Escalation: CD19 CAR T Cells for B-cell NHL/CLL Experimental Treatment 1 Intervention

Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

Group IV: Dose Escalation: CD19 CAR T Cells for B-cell ALL Experimental Treatment 1 Intervention

Each patient will receive a dose of CD19 CAR T Cells administered as an infusion. Each infusion will consist of CD19.CAR/28 T cells and CD19.CAR/28137 T cells.

CD19.CAR/28 and CD19.CAR/28137 T cells is already approved in United States for the following indications:

Approved in United States as CD19.CAR/28 T cells for:

• Non-Hodgkin Lymphoma
• Acute Lymphocytic Leukemia
• Chronic Lymphocytic Leukemia

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

The Methodist Hospital Research Institute

Collaborator

Trials

299

Recruited

82,500+

Published Research Related to This Trial

The study found that high levels of leukemia blast contamination in the starting material did not negatively impact the manufacturing of CAR T-cells or their ability to expand, suggesting that CAR T-cell therapy can be safely produced even from contaminated samples.

Using a specific CAR design with a short linker (CAR.CD19 SL) enhances the ability of CAR T-cells to target and kill CD19+ leukemia cells, providing a potential safety advantage in preventing leukemic relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Strategy to prevent epitope masking in CAR.CD19+ B-cell leukemia blasts. Quintarelli, C., Guercio, M., Manni, S., et al.[2022]

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 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]

CD37CAR T cells have shown comparable efficacy to CD19CAR T cells in controlling tumor growth in both in vitro and in vivo models, making them a promising alternative for treating B-cell lymphomas.

Unlike CD19CAR T cells, CD37CAR T cells effectively target tumors that have lost CD19 expression, demonstrating their potential to overcome resistance in patients with relapsed/refractory B-cell non-Hodgkin lymphoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preclinical development of CD37CAR T-cell therapy for treatment of B-cell lymphoma. Köksal, H., Dillard, P., Josefsson, SE., et al.[2020]

CD19CAR-T cell therapy is effective in treating relapsed and refractory B-lineage acute lymphoblastic leukemia, with four out of five patients achieving complete remission and minimal residual disease negativity.

The therapy can be safely administered with real-time monitoring of a 6-cytokine pattern, allowing for effective management of side effects like cytokine release syndrome and neurotoxicity using tocilizumab and steroids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor T cell therapy can be administered safely under the real-time monitoring of Th1/Th2 cytokine pattern using the cytometric bead array technology for relapsed and refractory acute lymphoblastic leukemia in children. Shen, D., Song, H., Xu, X., et al.[2021]

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]

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]

Adoptive cellular therapy using CD19 CAR T cells has shown remarkable efficacy in achieving remission in 67-90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), indicating a promising treatment option for this high-risk group.

While CD19 CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome and neurologic dysfunction, these effects are generally manageable with supportive care, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-redirected chimeric antigen receptor-modified T cells: a promising immunotherapy for children and adults with B-cell acute lymphoblastic leukemia (ALL). Tasian, SK., Gardner, RA.[2020]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11022988/

Efficacy and safety of CD19-specific CAR T cell–based ... Neurotoxicity of CD19 CAR T-cell therapy was acceptable in patients with relapsed/refractory B-ALL with CNSL. •. CD19-specific CAR T cells could induce similar ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10786140/

CAR-T Cell Therapy in B-Cell Acute Lymphoblastic Leukemia CAR-T cells targeting membrane antigens expressed on B-lymphoid cells, such as CD19, CD20, or CD22, were shown to have significant therapeutic activity in the ...

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1709919

Long-Term Follow-up of CD19 CAR Therapy in Acute ... Multiple clinical trials of CD19-specific CAR T cells have shown complete remission rates of 70 to 90% among children and adults with relapsed B ...

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

The present and future of CAR T-cell therapy for adult B- ... Chimeric antigen receptor T-cell therapy (CAR-T) targeting CD19 has transformed the management of relapsed/refractory (R/R) B-cell acute ...

5. 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 ... Discussion: CAR T-cell therapy, particularly anti-CD19, shows substantial efficacy in achieving MRD-CR in r/r B-ALL patients. The combination of ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT01853631

Study Details | NCT01853631 | Activated T-Cells ... These CD19 chimeric receptor T cells with CD28 and with or without CD137 are investigational products not approved by the FDA. The purpose of this study is to ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6277484/

In Vivo Fate and Activity of Second- versus Third-Generation ... We designed a clinical trial in which two CD19-specific CAR-transduced T cell products (CD19.CARTs) were prepared in parallel from autologous peripheral blood ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12117732/

Efficacy and safety of third-generation CD19-CAR T cells ... Case reports and small trials indicate that CD19-directed CAR T cell therapy is a safe and effective treatment strategy in R/R B-cell ...

9. nature.com nature.com/articles/s41375-024-02392-7

Third-generation anti-CD19 CAR T cells for relapsed ... We performed the first phase 1/2 investigator-initiated trial evaluating escalating doses of third-generation CARTs (HD-CAR-1) targeting CD19 in patients with ...

10. ashpublications.org ashpublications.org/blood/article/134/26/2361/409163/Toxicity-and-response-after-CD19-specific-CAR-T

Toxicity and response after CD19-specific CAR T-cell therapy ... We present results of a clinical trial that show the safety of CD19-specific CAR T-cell therapy for R/R B-ALL.