CAR T-Cell Therapy for Leukemia

Overseen By Aimee C. Talleur, MD

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: St. Jude Children's Research Hospital

Must not be taking: Systemic steroids, Intrathecal chemotherapy

Disqualifiers: HIV, CNS-3 disease, uncontrolled infection, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new CAR T-cell therapy (CD19-CAR(Mem) T-cells) to determine its safety and optimal dose for treating certain types of leukemia in young patients. It targets children and young adults with leukemia that has returned or not responded to treatment. The trial includes two groups: one for those who have received a stem cell transplant from the same donor and another for those who have not. Eligible participants are 21 years old or younger, have CD19-positive leukemia that is relapsed or difficult to treat, and have experienced challenges with other CAR T-cell therapies. As a Phase 1 trial, this research aims to understand 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 protocol suggests that you may need to stop certain medications. Specifically, you should not be on systemic steroids exceeding a certain dose or any systemic therapy that might interfere with the CAR T-cell product within 14 days before the infusion. Additionally, intrathecal chemotherapy should not be taken within 7 days prior to the infusion.

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

Research shows that CD19-CAR T-cells hold promise for treating difficult leukemia cases. These cells are a type of immunotherapy, helping the body's immune system fight cancer. Previous studies indicate that participants have generally tolerated CD19-CAR T-cells well. Common side effects include fever and low blood pressure, but these are usually manageable.

Donor-derived versions of these T-cells, like those in this study, have also been researched. They have been found safe for treating acute lymphoblastic leukemia (ALL), a type of blood cancer. Using donor T-cells might help more patients reach remission, meaning the cancer is no longer detectable.

This trial is in its early phase, so researchers are closely monitoring how the treatment affects people. They aim to find the best dose that balances safety and effectiveness. While early results are encouraging, this trial will provide more detailed information about safety for young patients with leukemia. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about CD19-CAR(Mem) T-cells because they offer a personalized approach to treating leukemia. Unlike traditional treatments like chemotherapy and radiation, which attack both healthy and cancerous cells, CAR T-cell therapy harnesses the body's own immune system to specifically target and destroy leukemia cells. This therapy involves modifying a patient's T-cells to better recognize and fight cancer cells, potentially leading to fewer side effects and a more effective treatment. Additionally, CD19-CAR(Mem) T-cells may provide a longer-lasting defense against cancer recurrence, making this a promising advancement in leukemia treatment.

What evidence suggests that CD19-CAR T-cells might be an effective treatment for leukemia?

Research has shown that CAR T-cell therapy, which targets the CD19 protein, offers promising results for B-cell acute lymphoblastic leukemia, particularly when the cancer returns or resists other treatments. Earlier studies demonstrated that these specially engineered T-cells can reduce or even eliminate the cancer temporarily. In this trial, participants will receive CD19-CAR T-cells, which specifically find and attack cancer cells with the CD19 marker. However, some cancer cells may lose this marker, potentially allowing the cancer to return. Despite this challenge, the therapy has succeeded in many cases where other treatments failed. These early successes suggest that CD19-CAR T-cells could provide hope for patients whose leukemia hasn't responded to other treatments. ^{1 2 4 6 7}

Who Is on the Research Team?

Aimee C. Talleur, MD

Principal Investigator

St. Jude Children's Research Hospital

Stephen Gottschalk, MD

Principal Investigator

St. Jude Children's Research Hospital

Are You a Good Fit for This Trial?

This trial is for young patients (≤ 21 years old) with relapsed or refractory CD19-positive leukemia who haven't responded to previous treatments and are not suitable for autologous CD19-CAR T-cell therapy. They should have a matched family member donor, good heart, kidney, liver function, no severe infections or significant arrhythmias, and must agree to birth control if sexually active.

Inclusion Criteria

I can do most activities but may need help.

EKG without evidence of clinically significant arrhythmia

My condition relapsed after a stem cell transplant from a donor.

Exclusion Criteria

Not applicable.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive allogeneic CD19-CAR.CD45RA-negative T-cells with dose escalation to determine the maximum tolerated dose

4 weeks

Weekly visits for dose escalation and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of dose-limiting toxicities

4 weeks

Bi-weekly visits for safety monitoring

Exploratory Analysis

Study of T-cell expansion, persistence, phenotype, and cytokine profile in peripheral blood and CSF

Ongoing

What Are the Treatments Tested in This Trial?

Interventions

• CD19-CAR(Mem) T-cells

Trial Overview The study tests the safety and maximum tolerated dose of allogeneic memory T-cells expressing a CD19-specific CAR in children and young adults with leukemia. It aims to find out how well these cells work against leukemia without causing graft-versus-host disease.

How Is the Trial Designed?

Group I: Group B Experimental Treatment 6 Interventions

Participants in group B have not received a prior stem cell transplant from their CAR T-cell donor.

Group II: Group A Experimental Treatment 6 Interventions

Participants in group A have received a prior stem cell transplant from their CAR T-cell donor.

CD19-CAR(Mem) T-cells is already approved in United States, European Union for the following indications:

Approved in United States as CD19-CAR T-cells for:

• Relapsed/Refractory CD19-positive leukemia

Approved in European Union as CD19-CAR T-cells for:

• Relapsed/Refractory CD19-positive leukemia

Who Is Running the Clinical Trial?

St. Jude Children's Research Hospital

Lead Sponsor

Trials

451

Recruited

5,326,000+

Published Research Related to This Trial

Allogeneic stem cell transplantation (alloSCT) is a powerful treatment for leukemia, leveraging the body's immune system to target and eliminate cancer cells, but it carries risks like graft-versus-host disease (GvHD).

Recent advancements in T-cell engineering and the identification of specific leukemia antigens have led to promising clinical trials, particularly with anti-CD19 CAR T-cells, showing significant potential in treating various types of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive T-cell therapy for Leukemia. Garber, HR., Mirza, A., Mittendorf, EA., et al.[2023]

The study introduces an innovative oncolytic vaccinia virus that creates truncated CD19 expression in solid tumors, enhancing the targeting ability of CD19-specific CAR-T cell therapies.

In both immunodeficient and immunocompetent mouse models, this approach effectively eradicates solid tumors, suggesting a promising strategy to improve CAR-T cell therapy outcomes in treating hematopoietic malignancies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combination Therapy for Solid Tumors: Taking a Classic CAR on New Adventures. Dagher, O., King, TR., Wellhausen, N., et al.[2021]

Allogeneic donor CAR19 T cells show potential as an effective treatment for refractory CD19+ acute lymphoblastic leukemia (ALL) in a mouse model, addressing challenges with autologous CAR T cell production due to patient T-cell dysfunction.

This study suggests that using CAR19 T cells from healthy donors could be a viable alternative for patients who struggle to produce their own functional T cells, potentially improving treatment outcomes for ALL.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic CAR19 cells clear ALL. Neeson, P.[2021]

A new strategy has been developed to create virus-specific T cells from donor blood that can be genetically modified to target leukemia cells, specifically those expressing the CD19 marker, which could help prevent or treat leukemia relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT).

The modified T cells showed similar activation and effectiveness in killing leukemia cells when stimulated through either the chimeric antigen receptor (CAR) or their natural T cell receptor (TCR), indicating that this approach could provide a robust method for targeted leukemia therapy while minimizing the risk of graft-versus-host disease (GVHD).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Generation of CD19-chimeric antigen receptor modified CD8+ T cells derived from virus-specific central memory T cells. Terakura, S., Yamamoto, TN., Gardner, RA., et al.[2023]

The study successfully developed a clinical-grade manufacturing process for allogeneic CD19-CAR T cells using donor memory T cells, which expanded significantly (34.2-fold) and showed effective CAR expression (45.5%).

These engineered CD19-CAR T cells demonstrated the ability to recognize and kill CD19-positive cancer cells in laboratory tests and exhibited strong antitumor activity in a model of acute lymphoblastic leukemia (ALL), indicating their potential as a viable treatment option for patients who cannot use autologous CAR T cell therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of a cGMP-compliant process to manufacture donor-derived, CD45RA-depleted memory CD19-CAR T cells. Kim-Hoehamer, YI., Riberdy, JM., Zheng, F., et al.[2023]

CAR T cell therapy, specifically targeting the CD19 antigen, has shown high response rates in patients with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL), indicating its potential as a new treatment option.

Despite its effectiveness, CAR T cell therapy is associated with severe toxicities like cytokine release syndrome and neurotoxicity, which pose challenges for its widespread use and highlight the need for ongoing improvements in the technology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. Luskin, MR., DeAngelo, DJ.[2018]

In a study involving 7 patients with B-cell acute lymphoblastic leukemia (B-ALL), all participants achieved complete remission in the bone marrow after receiving CD19 CAR-T cell therapy, demonstrating the treatment's efficacy.

However, within a month of treatment, 2 patients developed acute myeloid leukemia (AML) related to their original B-ALL, highlighting a potential risk of immune escape and the need for careful monitoring in patients undergoing this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy. Gardner, R., Wu, D., Cherian, S., et al.[2022]

CD19-specific CAR T-cell therapy shows high initial remission rates (over 80%) in pediatric patients with relapsed or refractory B-ALL, but only 40% to 50% achieve durable remission.

The review discusses the potential benefits of consolidative hematopoietic cell transplantation for patients who achieve a complete response after CAR T-cell therapy, as well as strategies to enhance the effectiveness and longevity of CAR T cells in preventing relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Preventing relapse after CD19 CAR T-cell therapy for pediatric ALL: the role of transplant and enhanced CAR T cells. Talleur, AC., Naik, S., Gottschalk, S.[2023]

CAR-T-cell therapy has shown significant promise in treating relapsed or refractory B-cell malignancies, such as B-cell non-Hodgkin lymphoma and B-cell acute lymphoblastic leukemia, by targeting specific antigens like CD19 and BCMA.

The review highlights both the efficacy and toxicity of CD19- and BCMA-targeted CAR-T-cell therapies, indicating that while these treatments can be effective, they also come with potential side effects that need to be managed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor-T-Cell Therapy for B-Cell Hematological Malignancies: An Update of the Pivotal Clinical Trial Data. Roex, G., Feys, T., Beguin, Y., et al.[2020]

CAR T-cell therapy, particularly targeting CD19, has shown high complete response rates in patients with relapsed or refractory B-cell malignancies, offering hope for those with limited treatment options.

While CAR T-cell therapy can lead to significant toxicities such as cytokine release syndrome, these can be effectively managed, and sustained B-cell aplasia may indicate long-term disease control in responding patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric Antigen Receptor T-Cell Therapy for the Community Oncologist. Maus, MV., Levine, BL.[2021]

CAR-T cell therapy targeting CD19 has shown remarkable success in treating refractory/relapsed acute lymphoblastic leukemia (ALL), achieving complete remission rates as high as 90% in both children and adults.

While CAR-T therapy is promising for hematologic cancers, challenges remain for its application in solid tumors due to immunosuppressive environments, and there are significant risks of severe toxicities like cytokine release syndrome (CRS) and neurotoxicity that require careful management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chimeric antigen receptor modified T-cells for cancer treatment. Han, X., Wang, Y., Han, WD.[2020]

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]

Adoptive T cell immunotherapy, particularly using tumor infiltrating lymphocytes (TILs), has shown the ability to induce significant cancer regression in metastatic melanoma, highlighting its potential effectiveness in cancer treatment.

The development of anti-CD19 CAR-T cells has marked a significant advancement in treating refractory B lymphocyte leukemia, but challenges remain in creating a standardized method for generating effective anti-leukemia T cells for all patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Approaches for generation of anti-leukemia specific T cells. Jin, Z., Xu, L., Li, Y.[2020]

In a phase 1 trial involving 6 patients with relapsed/refractory B-ALL, bispecific CAR T cell therapy targeting both CD19 and CD22 achieved a complete remission (CR) rate of 100%, demonstrating its potent anti-leukemic activity.

The therapy was found to be safe, with no neurotoxicity reported, although one patient experienced a relapse with CD19-negative leukemia, highlighting the challenge of antigen escape in treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bispecific CAR-T cells targeting both CD19 and CD22 for therapy of adults with relapsed or refractory B cell acute lymphoblastic leukemia. Dai, H., Wu, Z., Jia, H., et al.[2021]

Citations

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CAR-T cell therapy for cancer: current challenges and ... This review begins with a comprehensive overview of CAR-T cell therapy for cancer, covering the structure of CAR-T cells and the history of their clinical ...

2. 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 ...

3. thelancet.com thelancet.com/journals/ebiom/article/PIIS2352-3964(25)00316-0/fulltext

Tandem CD19/CD22 CAR T-cells as potential therapy for ... Chimeric antigen receptor (CAR) T-cells targeting CD19 have shown impressive outcomes in refractory/relapsed B-cell acute lymphoblastic ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6486329/

CD19 CAR T cell product and disease attributes predict ... Chimeric antigen receptor (CAR) T cells can induce remission in highly refractory leukemia and lymphoma subjects, yet the parameters for achieving sustained ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT05707273

Study Details | NCT05707273 | CD19-Car T Cell Therapy ... This phase I trial tests the safety, side effects, and best dose of autologous anti-CD19 CAR-expressing T lymphocytes (CD19-CAR T cells) in older adults ...

6. stjude.org stjude.org/care-treatment/clinical-trials/memcar19-leukemia.html

MEMCAR19: Allogeneic CAR T-Cell Therapy for Relapsed/ ... This clinical trial evaluates a type of immunotherapy that uses donor memory T cells to treat patients with relapsed or refractory CD19-positive leukemia.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05164042

Allogeneic CD19 CAR-T Cells for the Treatment of ... Allogeneic CAR-T cells are safe and effective for the treatment of ALL, and their clinical application range is expected to improve the remission rate and ...