CAR T Cell Therapy for Acute Lymphoblastic Leukemia

Recruiting in Palo Alto (17 mi)

Overseen by Marc Schwartz, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: University of Colorado, Denver

Disqualifiers: Previous CAR T, CNS disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

This trial tests a new treatment using modified immune cells to target and destroy remaining cancer cells in adults with B-ALL who are in remission but still have some cancer left. The goal is to see if this approach is safe and effective. Modified immune cells have shown remarkable success in helping patients with recurring B-ALL achieve remission again.

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.

What data supports the effectiveness of the treatment UCD19 CAR T Cells for Acute Lymphoblastic Leukemia?

Research shows that similar treatments, like CD19 CAR T cells, have high remission rates in patients with relapsed or refractory acute lymphoblastic leukemia, with one study reporting a 90% remission rate. This suggests that UCD19 CAR T Cells could also be effective in treating this condition. ^{1 2 3 4 5}

What is the safety profile of CAR T cell therapy for acute lymphoblastic leukemia?

CAR T cell therapy for acute lymphoblastic leukemia can cause side effects like cytokine release syndrome (a severe immune reaction) and neurological issues, but these are often manageable with treatments like tocilizumab and corticosteroids. Serious side effects are less common in real-world settings due to better management, and ongoing studies are evaluating long-term safety. ^{6 7 8 9 10}

How is the UCD19 CAR T treatment different from other treatments for acute lymphoblastic leukemia?

The UCD19 CAR T treatment is unique because it uses the patient's own T cells, which are modified to specifically target and destroy leukemia cells, offering high remission rates even in cases where other treatments have failed. This personalized approach is different from traditional chemotherapy or radiation, as it directly harnesses the immune system to fight the cancer. ^{1 2 3 4 11}

Research Team

Marc Schwartz, MD

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

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.

My B-cell ALL is in its first complete remission.

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.

Trial Timeline

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

Treatment Details

Interventions

• UCD19 CAR T (CAR T-cell Therapy)

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.

Participant Groups

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+

Aviva Abosch

University of Colorado, Denver

Chief Medical Officer since 2019

MD

Uday B. Kompella

University of Colorado, Denver

Chief Executive Officer since 2015

PhD in Pharmaceutical Sciences

Findings from Research

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]

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]

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]

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]

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]

References

1. England 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. [2018]

2. United States pubmed.ncbi.nlm.nih.gov

Locally produced CD19 CAR T cells leading to clinical remissions in medullary and extramedullary relapsed acute lymphoblastic leukemia. [2019]

3. England pubmed.ncbi.nlm.nih.gov

Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. [2019]

4. United States 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. [2023]

5. England 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. [2023]

6. Japan pubmed.ncbi.nlm.nih.gov

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

7. England 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). [2020]

8. England pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Brexucabtagene Autoleucel for Treatment of Adults With Relapsed or Refractory B-Cell Precursor Acute Lymphoblastic Leukemia. [2022]

9. Greece pubmed.ncbi.nlm.nih.gov

Cluster of differentiation 19 chimeric antigen receptor T-cell therapy in pediatric acute lymphoblastic leukemia. [2020]

10. United States 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. [2022]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Beyond CD19: Opportunities for Future Development of Targeted Immunotherapy in Pediatric Relapsed-Refractory Acute Leukemia. [2022]