CD19.CAR-aNKT Cells for Lymphoma and Leukemia

Not currently recruiting at 1 trial location

Overseen By Mahshid Azamian

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: Baylor College of Medicine

Disqualifiers: Investigational agents, GVHD, HIV, others

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

Compensation: Varies

Number of Visits: 15

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment for patients with certain blood cancers, specifically lymphoma and leukemia, that have not responded to other treatments. Researchers combine special immune cells with a protein to enhance their ability to fight these cancers. The treatment involves CD19.CAR-aNKT cells, which are modified immune cells designed to target cancer cells more effectively. The goal is to determine the safest dose of these modified cells and assess their potential benefits. Individuals with lymphoma or leukemia that has relapsed or not responded to at least two treatments might be suitable for this trial. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new therapy.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, you cannot participate if you are currently receiving any investigational agents or have received cellular therapies in the past 6 weeks.

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

Research has shown that the treatment, called CD19.CAR-aNKT cells, has been safe in past studies. Recent data indicate that patients who received this therapy did not experience serious side effects such as nerve damage or a condition where donor cells attack the body. These results suggest that the treatment is well-tolerated so far. However, it is important to remember that this research remains in the early stages, and the main goal is to find the safest dose. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD19.CAR-aNKT cells because this treatment leverages a unique mechanism involving genetically engineered immune cells known as CAR-aNKT cells. Unlike traditional chemotherapy or standard CAR-T therapies, which use T-cells, this treatment uses a specialized type of immune cell called invariant natural killer T (iNKT) cells. These cells are designed to target and eliminate cancer cells more effectively, particularly in cases of refractory or relapsed B-cell non-Hodgkin lymphoma (NHL) and acute lymphoblastic leukemia (ALL). This innovative approach has the potential to offer a more targeted and potent immune response, which could lead to better outcomes for patients who have few remaining treatment options.

What evidence suggests that CD19.CAR-aNKT cells might be an effective treatment for lymphoma or leukemia?

Research shows that CD19 antibodies can treat lymphoma and leukemia by attaching to cancer cells and marking them for destruction. In this trial, participants will receive CD19.CAR-aNKT cells, which combine this antibody with NKT cells, a type of immune cell that can kill tumor cells. Studies indicate that modifying these cells to carry the CD19 antibody is generally safe and can lead to positive outcomes in patients with hard-to-treat B-cell cancers. Some studies have shown a 73% success rate in reducing cancer cells with similar treatments, suggesting a promising new approach to these challenging cancers. Participants in this trial will also receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine before the CD19.CAR-aNKT cell infusion. ^{1 6 7 8 9}

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 aged 3-75 with certain types of B-cell lymphoma or leukemia that have CD19 on their surface and have not responded to treatment. They must be in relatively good health, with proper liver and kidney function, no severe infections, and a reasonable life expectancy. Participants need to agree to use effective birth control during the study.

Inclusion Criteria

I am between 3 and 75 years old.

I have been diagnosed with a type of blood cancer that tests positive for CD19.

My ALL has not responded to at least two treatments.

Exclusion Criteria

I have had a moderate to severe reaction from a transplant.

I am not currently on experimental drugs or had cell therapy in the last 6 weeks.

I do not have any untreated serious infections.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Lymphodepletion Chemotherapy

Participants receive lymphodepletion chemotherapy with cyclophosphamide and fludarabine before ANCHOR cell infusion

1 week

1 visit (in-person)

ANCHOR Cell Infusion

Participants receive an infusion of ANCHOR cells and are monitored for immediate side effects

1 day

1 visit (in-person)

Initial Monitoring

Participants are monitored for side effects and cell persistence, with follow-up visits 3 times per week for the first 4 weeks

4 weeks

12 visits (in-person)

Extended Follow-up

Participants are monitored for long-term safety and effectiveness, with visits at specified intervals up to 15 years

15 years

Regular visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• CD19.CAR-aNKT cells
• Cyclophosphamide
• Fludarabine

Trial Overview The trial tests ANCHOR cells (CD19.CAR-aNKT), which are genetically modified immune cells designed to fight cancer by targeting CD19 on tumor cells. The goal is to determine the highest safe dose, how long these cells last in the body, their side effects, and if they help treat lymphoma or leukemia.

How Is the Trial Designed?

Group I: CD19.CAR-aNKT cells (cohort B, ALL). Experimental Treatment 1 Intervention

This cohort is for patients with refractory/relapsed B-cell NHL or leukemia (ALL). Three dose levels will be evaluated. Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion.

Group II: CD19.CAR-aNKT cells (cohort A, non-ALL) Experimental Treatment 1 Intervention

This cohort is for patients without refractory/relapsed B-cell NHL or leukemia (ALL). Three dose levels will be evaluated. Patients will also receive lymphodepletion chemotherapy consisting of cyclophosphamide and fludarabine followed by the CD19.CAR-aNKT cell infusion.

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+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Center for Cell and Gene Therapy, Baylor College of Medicine

Collaborator

Trials

114

Recruited

2,900+

Published Research Related to This Trial

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 phase I trial involving 12 younger patients with relapsed or refractory B-cell acute lymphoblastic leukemia, the use of chimeric antigen receptor T cells targeting CD19 and CD22 showed manageable toxicity levels.

Out of the 12 patients, 5 achieved complete responses, indicating promising efficacy of this treatment approach in this challenging patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting CD19-CD22 Aids Younger Patients with ALL. [2021]

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]

Chimeric antigen receptor (CAR) NK-cell therapy is being explored as a promising treatment for hematologic malignancies, particularly targeting the CD19 protein.

This approach is advantageous because NK cells do not cause graft-versus-host disease, allowing for their potential off-the-shelf use in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Equipping NK Cells with CARs. [2019]

Engineered NK-92 cells with anti-CD19 chimeric antigen receptors (αCD19-CAR) can effectively kill CD19-positive leukaemic cells that are typically resistant to natural killer cell activity, demonstrating significant cytotoxicity against both leukaemic cell lines and primary patient cells.

The safety of NK-92 cells has been established in phase I clinical studies, and their ability to be expanded under Good Manufacturing Practice (cGMP) conditions makes CAR-modified NK-92 cells a promising treatment option for patients with lymphoid malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CD19-CAR engineered NK-92 cells are sufficient to overcome NK cell resistance in B-cell malignancies. Romanski, A., Uherek, C., Bug, G., et al.[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]

In a study involving 15 patients with advanced CD19(+) B-cell malignancies, 8 patients achieved complete remissions after receiving autologous anti-CD19 CAR T cells, demonstrating the treatment's efficacy, especially in chemotherapy-refractory diffuse large B-cell lymphoma (DLBCL).

While the treatment showed promising results, some patients experienced acute toxicities such as fever and delirium, which resolved within three weeks, indicating that while the therapy is effective, monitoring for side effects is essential.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chemotherapy-refractory diffuse large B-cell lymphoma and indolent B-cell malignancies can be effectively treated with autologous T cells expressing an anti-CD19 chimeric antigen receptor. Kochenderfer, JN., Dudley, ME., Kassim, SH., 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]

Anti-CD19 CAR T-cell therapy has demonstrated significant clinical activity in treating B-cell non-Hodgkin lymphoma (NHL), with objective response rates ranging from 50-83% for relapsed diffuse large B-cell lymphoma (DLBCL), 83-93% for follicular lymphoma (FL), and 93% for mantle cell lymphoma (MCL).

This therapy represents a promising treatment option for patients with poor-risk refractory B-cell NHLs, highlighting its potential efficacy in difficult-to-treat cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anti-CD19 chimeric antigen receptor T-cell therapy in B-cell lymphomas: current status and future directions. Chavez, JC., Yassine, F., Sandoval-Sus, J., 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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03774654

Study Details | NCT03774654 | CD19.CAR Allogeneic NKT ... CD19 antibodies have been used to treat people with lymphoma and leukemia. For this study, the anti-CD19 antibody has been changed so that instead of floating ...

2. biospace.com biospace.com/athenex-presents-interim-data-from-anchor-study-of-kur-502-allogeneic-cd19-car-nkt-cells-in-relapsed-or-refractory-lymphoma-and-leukemia-at-63rd-ash-annual-meeting-and-exposition

Athenex Presents Interim Data from ANCHOR Study of ... The data demonstrates that allogeneic CD19 CAR-NKT cells are well-tolerated and can mediate objective responses in B-cell relapsed/refractory ...

3. mdanderson.org mdanderson.org/newsroom/cd19-car-nk-cell-therapy-achieves-73-percent-response-rate-in-patients-with-leukemia-and-lymphoma.h00-159379578.html

CD19 CAR NK-cell therapy achieves 73% response rate ... Responses to the CD19 CAR NK cell therapy were evident within one month following infusion, and persistence of these cells was confirmed out to ...

4. nejm.org nejm.org/doi/full/10.1056/NEJMoa1910607

Use of CAR-Transduced Natural Killer Cells in CD19 ... Anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has shown remarkable clinical efficacy in B-cell cancers. However, CAR T cells can ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10140490/

Failure of ALL recognition by CAR T cells: a review of CD 19 ... The aim of this review is to summarize the biological mechanisms described as causing the loss of CD19 antigen and subsequent leukemia escape after anti-CD19 ...

6. firstwordpharma.com firstwordpharma.com/story/5435917

Athenex Presents Interim Data from ANCHOR Study of ... Updated data show continued favorable safety profile and encouraging anti-tumor activity in adult patients treated with low doses of KUR-502.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8873350/

Allogeneic Chimeric Antigen Receptor Therapy in Lymphoma Delay in CAR-T therapy and increase in the lines of therapy before CAR-T have both been shown to worsen outcomes along with an increase in tumor ...

8. biospace.com biospace.com/athenex-presents-interim-data-from-phase-1-anchor-study-of-kur-502-allogeneic-cd19-car-nkt-cells-in-relapsed-or-refractory-lymphoma-and-leukemia-at-the-2022-transplantation-and-cellular-tandem-meetings-of-astct-and-cibmtr

Athenex Presents Interim Data from Phase 1 ANCHOR ... Excellent safety with no immune effector cell-associated neurotoxicity syndrome (ICANS) and no graft versus host disease (GvHD) attributable to ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S2666634025001047

Emerging trends in clinical allogeneic CAR cell therapy Recent clinical trials have demonstrated sustained and significant elimination of autoreactive B cells through autologous CD19- and/or BCMA- ...