CAR T-Cell Therapy for Acute Lymphoblastic Leukemia
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Crystal Mackall, MD
Must not be taking: Anticoagulants
Disqualifiers: CNS disorders, Cardiac disease, Infections, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial studies a new treatment combining modified immune cells and chemotherapy for children and young adults with difficult-to-treat leukemia. The immune cells are engineered to target and kill cancer cells, while chemotherapy helps them work more effectively.
Do I need to stop my current medications for the trial?
The trial protocol does not specify if you must stop all current medications, but it does mention that certain chemotherapy drugs should be stopped at least one week before apheresis (a procedure to collect blood cells). It's best to discuss your specific medications with the trial team to get a clear answer.
What data supports the effectiveness of the treatment Chimeric Antigen Receptor T-Cell Therapy for Acute Lymphoblastic Leukemia?
Research shows that CAR T-cell therapies like tisagenlecleucel and axicabtagene ciloleucel are highly effective for treating relapsed or refractory B-cell acute lymphoblastic leukemia, significantly improving survival rates and achieving long-term remissions in many patients.
12345Is CAR T-cell therapy safe for humans?
CAR T-cell therapy, including treatments like tisagenlecleucel and axicabtagene ciloleucel, has been approved for certain cancers and shows promising results, but it can cause serious side effects. Patients may experience cytokine release syndrome (a severe immune reaction), neurotoxicity (nerve damage), and infections, which require careful monitoring and management.
678910How is CAR T-cell therapy different from other treatments for acute lymphoblastic leukemia?
CAR T-cell therapy is unique because it uses genetically modified T-cells (a type of immune cell) to specifically target and destroy cancer cells in patients with relapsed or refractory B-cell acute lymphoblastic leukemia. This treatment is particularly effective for patients who have not responded to standard therapies, offering a new option for those with limited alternatives.
12101112Eligibility Criteria
This trial is for children and young adults aged 1 to 30 with B-cell acute lymphoblastic leukemia that's resistant or has returned after treatment. They should have tried at least two therapies, be free of uncontrolled infections, not pregnant or breastfeeding, and without severe heart conditions. Participants must also have no history of certain other diseases within the last three years.Inclusion Criteria
Must have evaluable or measurable disease according to the revised IWG Response Criteria for Malignant Lymphoma
My condition worsened after a stem cell transplant.
My minimal residual disease has been confirmed positive twice, at least 4 weeks apart.
+19 more
Exclusion Criteria
I do not have brain disorders that could affect nerve damage assessment.
Unlikely to complete all protocol-required study visits or procedures
My ALL has come back or didn't respond to treatment, and is only in my testicles.
+11 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Chemotherapy
Participants receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2
1 week
3 visits (in-person)
CAR T Cell Treatment
Participants receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Additional doses may be given if beneficial and no unacceptable side effects occur
1 day
1 visit (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
15 years
Daily until day 14, twice weekly until day 28, at 2 and 3 months, every 3 months until month 12, every 6-12 months up to year 5, then annually for years 6-15
Participant Groups
The study tests different doses of CD19/CD22 CAR T cells combined with chemotherapy (fludarabine phosphate and cyclophosphamide) in patients whose leukemia expresses CD19 proteins. It aims to find the best dose that is effective while monitoring side effects.
1Treatment groups
Experimental Treatment
Group I: Treatment (CD19/CD22-CAR T cells, chemotherapy)Experimental Treatment5 Interventions
Patients receive fludarabine phosphate IV over 30 minutes on days -4 to -2 and cyclophosphamide IV over 60 minutes on day -2. Patients then receive CD19/CD22-CAR T cells IV over 10-20 minutes on day 0. Patients that benefited from the first dose of CD19/CD22-CAR T cells, had no unacceptable side effects, and have enough cells left over may receive 2 or 3 additional doses of CD19/CD22-CAR T cells.
Chimeric Antigen Receptor T-Cell Therapy is already approved in European Union, United States, European Union, United States, European Union, United States, European Union, United States, European Union, United States, Canada, Japan for the following indications:
🇪🇺 Approved in European Union as Tisagenlecleucel for:
- Acute lymphoblastic leukemia
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇺🇸 Approved in United States as Tisagenlecleucel for:
- Acute lymphoblastic leukemia
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇪🇺 Approved in European Union as Axicabtagene ciloleucel for:
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇺🇸 Approved in United States as Axicabtagene ciloleucel for:
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇪🇺 Approved in European Union as Tecartus for:
- Mantle cell lymphoma
- Acute lymphoblastic leukemia
🇺🇸 Approved in United States as Tecartus for:
- Mantle cell lymphoma
- Acute lymphoblastic leukemia
🇪🇺 Approved in European Union as Brexucabtagene autoleucel for:
- Mantle cell lymphoma
🇺🇸 Approved in United States as Brexucabtagene autoleucel for:
- Mantle cell lymphoma
🇪🇺 Approved in European Union as Lisocabtagene maraleucel for:
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇺🇸 Approved in United States as Lisocabtagene maraleucel for:
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇨🇦 Approved in Canada as CAR T-cell therapy for:
- Acute lymphoblastic leukemia
- Diffuse large B-cell lymphoma
- Follicular lymphoma
🇯🇵 Approved in Japan as CAR T-cell therapy for:
- Acute lymphoblastic leukemia
- Diffuse large B-cell lymphoma
- Follicular lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Lucile Packard Children's Hospital Stanford UniversityPalo Alto, CA
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Who Is Running the Clinical Trial?
Crystal Mackall, MDLead Sponsor
References
CD19 chimeric antigen receptor-T cells in B-cell leukemia and lymphoma: current status and perspectives. [2022]The approval of tisagenlecleucel and axicabtagene ciloleucel represents a breakthrough in the field of immune and cellular therapy for hematologic malignancies. These anti-CD19 chimeric antigen receptor-T cells (CAR) proved to be highly effective in the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia (B-ALL) and specific histologic subtypes of B-cell non-Hodgkin lymphomas. This expert review aims to summarize the current available research evidence in this field, with a special focus on the different challenges faced by treating physicians, and we also provide future perspectives.
Clinical Pharmacology of Tisagenlecleucel in B-cell Acute Lymphoblastic Leukemia. [2020]Tisagenlecleucel is an anti-CD19 chimeric antigen receptor (CAR19) T-cell therapy approved for the treatment of children and young adults with relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL).
Tisagenlecleucel for the treatment of B-cell acute lymphoblastic leukemia. [2022]Cure rates for pediatric and young adult patients with refractory or recurrently relapsed acute lymphoblastic leukemia (ALL) are dismal. Survival from time of relapse is typically measured in weeks to months, and standard chemotherapy and currently approved targeted therapy achieve remission in less than a third of affected patients. To date, the only definitive curative therapy has been allogeneic hematopoietic stem cell transplant (HSCT). Advances in immunotherapy, with the introduction of chimeric antigen receptor T-cell therapies and the development of tisagenlecleucel, have changed the landscape. Areas covered: This review will describe the pharmacology of tisagenlecleucel and summarize the clinical evidence for its use in the treatment of multiple-relapsed or refractory B-cell ALL (B-ALL). Also discussed are other immunotherapies for B-ALL as well as the most commonly-encountered toxicities and corresponding management strategies. Expert commentary: Early phase trials indicate that tisagenlecleucel significantly improves survival for patients with B-ALL that is refractory or in second or later relapse. In responding patients, remissions have been reported on the order of years, and thus, tisagenlecleucel may herald a dramatic shift in the treatment paradigm of this largely fatal disease.
Clofarabine for Lymphodepletion Before CAR-T-Cell Infusion: A Brief Case Report. [2023]Given the shortage of fludarabine, alternative preparative lymphodepleting regimens for CAR-T-cell therapy need to be identified. We present a case of relapsed/refractory B-cell acute lymphoblastic leukemia requiring multiple lines of salvage therapy with persistent extensive disease, who underwent lymphodepletion with clofarabine and cyclophosphamide before tisagenlecleucel CD19+ CAR-T-cell infusion with eventual remission. We offer evidence of clofarabine's activity against B-cell acute lymphoblastic leukemia in combination with tisagenlecleucel therapy. In this patient, clofarabine did not decrease CAR-T-cell effectiveness, supported by presence of cytokine release syndrome and ultimate minimal residual disease negativity both on flow cytometry and next-generation sequencing.
Chimeric Antigen Receptor T Cells in Large B-Cell Lymphoma: Analysis of Overall Survival Based on Reconstructed Patient-Level Data. [2022]Chimeric antigen receptor (CAR) T-cell products (eg, tisagenlecleucel [tisa], axicabtagene ciloleucel [axi]) have been used in patients with relapsed/refractory large B-cell lymphoma (LBCL) and in adult patients with acute lymphoblastic leukemia (ALL). After the recent publication of long-term follow-up data in LBCL, reviewing the evidence on this topic is worthwhile. The aim of the present work was to study the pattern of overall survival (OS) reported for CAR T-cell products in LBLC and ALL.
Efficacy and Safety of CAR-T Cell Products Axicabtagene Ciloleucel, Tisagenlecleucel, and Lisocabtagene Maraleucel for the Treatment of Hematologic Malignancies: A Systematic Review and Meta-Analysis. [2022]Currently, three chimeric antigen receptor (CAR)-T cell products axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel have been approved by the U.S. Food and Drug Administration for the treatment of large B cell lymphoma, which provide a novel and promising choice for patients with relapsed or refractory to traditional anti-tumor treatments. Thus, it is pertinent to describe the efficacy and safety profile of the three products available by summarizing the current evidence.
Safety profile of chimeric antigen receptor T-cell immunotherapies (CAR-T) in clinical practice. [2021]Two chimeric antigen receptor T-cell (CAR-T) therapies have been approved in the United States (USA) in 2017 and Europe (EU) in 2018: axicabtagene ciloleucel and tisagenlecleucel. They contain the patient's own T cells, which are extracted, genetically modified, and reinfused. Alongside the good efficacy results, the assessment of safety profile of these new therapies represents a great challenge. Our aim was to analyze the reports of the adverse drug reactions (ADR) after CAR-T administration as occurred in the real clinical setting.
Tisagenlecleucel: The First CAR on the Highway to Remission for Acute Lymphoblastic Leukemia. [2020]Tisagenlecleucel is a first-in-class chimeric antigen receptor (CAR) T-cell therapy approved by the US Food and Drug Administration in 2017 for relapsed/refractory (RR) acute lymphoblastic leukemia (ALL) in patients up to 25 years of age. Tisagenlecleucel is an autologous T-cell therapy that is genetically engineered with a lentiviral vector to seek and eliminate CD19-expressing B cells throughout the patient's body and retain antitumor immune surveillance following remission. This groundbreaking cellular therapy brings unprecedented single-agent efficacy to patients with RR ALL, citing complete response rates of greater than 80% and 6-month relapse-free survivals exceeding 60% in a patient population with poor prognosis and few treatment options. Patients receiving CAR T-cell therapy are at risk for cytokine release syndrome (CRS), neurotoxicity, and infections, along with other toxicities that may be severe or life-threatening. The cornerstone of the management of moderate to severe CRS is treatment with the interleukin-6 antagonist tocilizumab, with dramatic responses often occurring within 24 hours. The optimal management of neurotoxicity following tisagenlecleucel remains undefined. It is critical that providers caring for patients receiving tisagenlecleucel understand the multistep process to prepare a patient for therapy, how to closely monitor patients for toxicity, and how to manage emergent adverse events following cell infusion.
Efficacy and safety of CD19-directed CAR-T cell therapies in patients with relapsed/refractory aggressive B-cell lymphomas: Observations from the JULIET, ZUMA-1, and TRANSCEND trials. [2022]Chimeric antigen receptor (CAR)-T cell therapies have improved the outcome for many patients with relapsed or refractory aggressive B-cell lymphomas. In 2017, axicabtagene ciloleucel and soon after tisagenlecleucel became the first approved CAR-T cell products for patients with high-grade B-cell lymphomas or diffuse large B-cell lymphoma (DLBCL) who are relapsed or refractory to ≥ 2 prior lines of therapy; lisocabtagene maraleucel was approved in 2021. Safety and efficacy outcomes from the pivotal trials of each CAR-T cell therapy have been reported. Despite addressing a common unmet need in the large B-cell lymphoma population and utilizing similar CAR technologies, there are differences between CAR-T cell products in manufacturing, pivotal clinical trial designs, and data reporting. Early reports of commercial use of axicabtagene ciloleucel and tisagenlecleucel provide the first opportunities to validate the impact of patient characteristics on the efficacy and safety of these CAR-T cell therapies in the real world. Going forward, caring for patients after CAR-T cell therapy will require strategies to monitor patients for sustained responses and potential long-term side effects. In this review, product attributes, protocol designs, and clinical outcomes of the key clinical trials are presented. We discuss recent data on patient characteristics, efficacy, and safety of patients treated with axicabtagene ciloleucel or tisagenlecleucel in the real world. Finally, we discuss postinfusion management and preview upcoming clinical trials of CAR-T cell therapies.
CD19 CAR T Cells for the Treatment of Pediatric Pre-B Cell Acute Lymphoblastic Leukemia. [2020]The development of cluster of differentiation (CD)-19-targeted chimeric antigen receptor (CAR) T cells for the treatment of pre-B-cell acute lymphoblastic leukemia (B-ALL) is an exciting new advancement in the field of pediatric oncology. Tisagenlecleucel and axicabtagene ciloleucel are the first US FDA-approved CD19-targeted CAR T cells. While various different CD19 CAR T cells are in development, tisagenlecleucel is the only CAR T cell approved for pediatric patients. The multicenter phase II trial that led to the approval of tisagenlecleucel demonstrated excellent responses in individuals with highly refractory disease. Other high-risk groups of patients with B-ALL who experience poor outcomes with standard therapy may also benefit from treatment with tisagenlecleucel. After receiving CAR T cells, patients must be closely monitored for unique toxicities, including cytokine release syndrome, neurotoxicity, and B-cell aplasia. The management of patients with relapsed or refractory disease after administration of CD19 CAR T cells can be challenging, and treatment options vary according to the characteristics of the disease present at relapse. In the many patients who experience a complete response, CAR T cells can lead to a durable remission. This review describes the current design and manufacturing of CAR T cells. Data in the selection and management of pediatric patients are highlighted, as are areas where further studies are needed.
Clinical experience of CAR T cells for B cell acute lymphoblastic leukemia. [2022]Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment for both pediatric and adult patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Clinical trial results across multiple institutions with different CAR constructs report significant response rates in treated patients. One product (tisagenlecleucel) is currently FDA approved for the treatment of R/R B-ALL in patients
First-Ever CAR T-cell Therapy Approved in U.S. [2021]The first chimeric antigen receptor T-cell therapy, tisagenlecleucel, received FDA approval for the treatment of patients up to 25 years of age with B-cell precursor acute lymphoblastic leukemia who haven't responded to standard therapy or who have relapsed at least twice.