CAR T Cell Therapy for Acute Lymphoblastic Leukemia

Overseen By Andrew Roth, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Colorado, Denver

Disqualifiers: Previous CAR T, CNS disease, others

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

Compensation: Varies

Number of Visits: Unknown

29 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called UCD19 CAR T cell therapy for individuals with acute lymphoblastic leukemia, specifically those in remission but with minimal residual disease (MRD), meaning small traces of cancer cells remain. The primary goal is to assess the safety and tolerability of this treatment and to identify the optimal dose. Participants will first undergo chemotherapy to prepare for the CAR T cell infusion. This trial suits adults in remission from B-cell acute lymphoblastic leukemia after initial treatment but with detectable cancer cells. 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 innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, since the trial involves chemotherapy and CAR T cell therapy, it's possible that some medications might need to be adjusted. Please consult with the trial coordinators for specific guidance.

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

Research has shown that UCD19 CAR T cell therapy can be safely administered to adults with acute lymphoblastic leukemia. In one study, seven patients received this treatment, and the early results were promising. Although side effects like nerve-related issues can occur, they have been reported as manageable.

This treatment remains in the early testing stages. The current focus is on assessing its safety and tolerability. Researchers are determining the optimal dose and are closely monitoring for any side effects.

Overall, UCD19 CAR T cell therapy has shown potential, but it is still under careful study to ensure its safety for wider use. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard chemotherapy and stem cell transplants for acute lymphoblastic leukemia, UCD19 CAR T therapy is unique because it harnesses the patient's own immune cells to fight the cancer. This treatment involves a cutting-edge technique where T cells are modified to specifically target and destroy leukemia cells. Researchers are excited about this approach because it offers a targeted attack on cancer cells, potentially leading to fewer side effects and more effective results compared to traditional methods.

What evidence suggests that this treatment might be an effective treatment for acute lymphoblastic leukemia?

Research shows that CAR T-cell therapy significantly advances the treatment of relapsed or hard-to-treat acute lymphoblastic leukemia (B-ALL). Studies have found that CD19 CAR T-cell therapies, such as UCD19, lead to high rates of long-lasting remission in adult B-ALL patients. Many patients experience major improvements, with many achieving remission after treatment. However, side effects can occur, and these treatments typically require close monitoring. Overall, UCD19 CAR T therapy shows promise in effectively treating B-ALL by targeting specific cancer cells. ^{5 6 7 8 9}

Who Is on the Research Team?

Marc Schwartz, MD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adults with B-cell ALL in first complete remission but still showing minimal residual disease can join this trial. They must be fit enough for treatment (ECOG ≤ 2), have adequate organ function, and not be pregnant or planning pregnancy. Excluded are those with previous CAR T therapy, active CNS leukemia, uncontrolled infections, HIV/hepatitis B/C, certain heart conditions, or a history of other cancers within 3 years.

Inclusion Criteria

I am capable of becoming pregnant and have a negative pregnancy test.

My side effects from previous treatments are mild or gone.

MRD positivity criteria for Ph- ALL and Ph+ ALL

Exclusion Criteria

My condition is either mixed phenotype acute leukemia or Burkitt's lymphoma.

My blood cancer is not in remission.

I am currently fighting an infection that needs medicine to manage.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Lymphodepleting Chemotherapy

Participants undergo apheresis and receive lymphodepleting chemotherapy prior to CAR T cell infusion

1-2 weeks

CAR T Cell Infusion

Infusion of UCD19 CAR T cells following chemotherapy, with potential delay for clinical toxicity resolution

1 week

Dose Limiting Toxicity Assessment

Assessment for dose limiting toxicities within 42 days after CAR T infusion

6 weeks

Follow-up

Participants are monitored for overall response rate, survival, and event-free survival

24 months

What Are the Treatments Tested in This Trial?

Interventions

• UCD19 CAR T

Trial Overview The trial is testing UCD19 CAR T cell therapy's safety and effectiveness in adults with acute lymphoblastic leukemia who are in remission but have some remaining cancer cells. It involves collecting patients' immune cells, modifying them to target cancer cells better and then infusing them back into the patient after chemotherapy.

How Is the Trial Designed?

Group I: UCD19 CAR T Infusion Experimental Treatment 1 Intervention

Lymphodepleting chemotherapy followed by infusion of UCD19 CAR T cells. Infusion is subject to a seven (7) day delay following chemotherapy completion if needed for resolution of clinical toxicities or to allow for product release.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Published Research Related to This Trial

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]

CD19 CAR T-cell therapy has shown a high complete remission rate in pediatric acute lymphoblastic leukemia, highlighting its efficacy as a treatment for this type of cancer.

Despite its effectiveness, CD19 CAR T-cell therapy is associated with significant adverse reactions and an increased risk of cancer recurrence, necessitating further research into mechanisms of recurrence and strategies to mitigate these risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cluster of differentiation 19 chimeric antigen receptor T-cell therapy in pediatric acute lymphoblastic leukemia. Fu, Z., Zhou, J., Chen, R., et al.[2020]

The FDA has approved tisagenlecleucel, the first anti-CD19 CAR T-cell therapy, specifically for treating pediatric and young adult patients with relapsed or refractory acute lymphocytic leukemia (ALL).

CAR T-cell therapy, particularly with tisagenlecleucel, shows promise as a standard treatment option for patients with B-cell malignancies, although it has primarily been developed through small clinical studies and poses unique management challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. Thomas, X., Paubelle, E.[2019]

Brexucabtagene autoleucel (brexu-cel) is an FDA-approved CAR T-cell therapy for adult patients with relapsed or refractory B-cell precursor acute lymphoblastic leukemia (B-ALL), showing a complete remission (CR) rate of 52% within 3 months after treatment in a study of 54 patients.

While brexu-cel demonstrates significant efficacy, it is associated with serious adverse reactions in 79% of patients, including severe cytokine release syndrome (92%) and neurological toxicities (87%), necessitating a risk evaluation and mitigation strategy (REMS) for patient safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. Bouchkouj, N., Lin, X., Wang, X., et al.[2022]

In a phase 1b/2 study involving 21 patients with relapsed and refractory acute lymphoblastic leukemia (R/R ALL), autologous CD19 CAR T cell therapy achieved a remarkable remission rate of 90%, including successful treatment of extramedullary leukemic sites.

While 16 patients experienced cytokine release syndrome and 11 had neurotoxicity, there were no toxic deaths, indicating that the treatment is relatively safe despite these side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. Jacoby, E., Bielorai, B., Avigdor, A., et al.[2019]

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]

A 71-year-old woman with relapsed and refractory acute lymphoblastic leukemia (ALL) achieved undetectable minimal residual disease after receiving haplo-identical donor-derived CD19 CAR-T cells combined with mobilized peripheral blood stem cells, indicating potential efficacy in treating elderly patients.

While the treatment led to full donor cell engraftment, it also caused transient cytokine release and mild fever, along with reversible increases in liver enzymes, highlighting the need for caution regarding complications from donor cell infusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Co-infusion of haplo-identical CD19-chimeric antigen receptor T cells and stem cells achieved full donor engraftment in refractory acute lymphoblastic leukemia. Cai, B., Guo, M., Wang, Y., et al.[2018]

CAR T cell therapy, particularly targeting CD19, has shown promising results in treating pediatric patients with relapsed and refractory B cell acute lymphoblastic leukemia (ALL), offering a new hope for those with high-risk disease.

The review highlights the need for exploring additional therapeutic targets for other high-risk leukemia types, such as T cell ALL, acute myeloid leukemia (AML), and infant ALL, to improve treatment outcomes in pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beyond CD19: Opportunities for Future Development of Targeted Immunotherapy in Pediatric Relapsed-Refractory Acute Leukemia. Shalabi, H., Angiolillo, A., Fry, TJ.[2022]

UCART19, a genome-edited allogeneic CAR T cell therapy, demonstrated feasibility and antileukaemic activity in 21 patients with relapsed or refractory B-cell acute lymphoblastic leukaemia, achieving a complete response in 67% of participants within 28 days after infusion.

While UCART19 showed promising efficacy, it was associated with significant adverse events, including cytokine release syndrome in 91% of patients, highlighting the need for careful monitoring and management of side effects during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Genome-edited, donor-derived allogeneic anti-CD19 chimeric antigen receptor T cells in paediatric and adult B-cell acute lymphoblastic leukaemia: results of two phase 1 studies. Benjamin, R., Graham, C., Yallop, D., et al.[2023]

CAR-T cell therapy, particularly with anti-CD19 CAR-T cells like Tisagenlecleucel (Kymriah®), has significantly improved treatment outcomes for pediatric patients with relapsed acute lymphoblastic leukemia (ALL), achieving high rates of remission.

While CAR-T therapy can lead to serious adverse events such as cytokine release syndrome and neurotoxicity, these are managed effectively in real-world settings, resulting in fewer severe complications compared to clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current status of CAR-T cell therapy for pediatric hematologic malignancies. Hiramatsu, H.[2023]

In a phase 1 trial involving 15 pediatric and young adult patients with relapsed or refractory B-ALL, the dual-targeting CAR T-cell therapy AUTO3 demonstrated a favorable safety profile with no severe toxicities reported and an impressive remission rate of 86% one month post-treatment.

Despite the high initial remission rate, the one-year overall survival rate was 60% and event-free survival rate was 32%, indicating that improvements in the persistence of AUTO3 CAR T-cells are necessary to enhance long-term outcomes and prevent relapses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Cordoba, S., Onuoha, S., Thomas, S., et al.[2022]

Citations

1. 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 ... CAR T-cell therapy represents a groundbreaking advancement in treating r/r B-ALL, offering high rates of durable remissions.

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.e19012

CD-19 CAR-T cell therapy in adult B-cell ALL patients This review assesses the efficacy and safety of various CD-19 CAR-T cell therapies tested in adult relapsed/refractory B-cell ALL patients.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12166372/

Real-world outcomes for young adult patients receiving CD19 ... This study demonstrates comparable real-world efficacy among YAs receiving CD19 CAR T irrespective of CAR T construct; however, rates of toxicity seem higher ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04544592

UCD19 CarT in Treatment of Pediatric B-ALL and B-NHL This phase I/II trial will investigate a new CD19 directed CAR-T therapy manufactured locally with the goals to expedite infusion to wider patient inclusion ...

5. cancer.gov cancer.gov/research/participate/clinical-trials/intervention/autologous-ucd19-car-t-cells?pn=1

Clinical Trials Using Autologous UCD19 CAR T Cells - NCI NCI supports clinical trials that test new and more effective ways to treat cancer. Find clinical trials studying autologous ucd19 car t cells.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT05535855

UCD19 CAR T Therapy in Adults With B-ALL and MRD ... This open-label, single arm Phase 1/1b trial aims to determine the safety and tolerability of anti-CD19 chimeric antigen receptor-expressing (CAR) T cells ...

7. ashpublications.org ashpublications.org/blood/article/144/Supplement%201/5876/527644/Use-of-CD19-CAR-T-Cells-in-Adult-B-Cell-Acute

Use of CD19 CAR-T Cells in Adult B-Cell Acute Lymphoblastic ... Conclusions: Thus far, UCD19 has been safely administered to 7 adult patients with B-ALL in MRD+ CR1. Early outcomes are promising with high ...

8. 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 ...

9. 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 ...