CAR-T Cell Therapy for B-Cell Leukemia
(TRICAR-ALL Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
Overseen ByNabil Ahmed, MD
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Baylor College of Medicine
Must not be taking: Corticosteroids, TKIs, Hydroxyurea, others
Disqualifiers: Active malignancy, Severe infection, Pregnancy, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests a new treatment for patients with a type of blood cancer called Acute Lymphoblastic Leukemia (ALL) that hasn't responded to other treatments. The treatment uses the patient's own T cells, which are modified in the lab to better fight cancer. These enhanced T cells are then reintroduced into the patient's body to target and kill cancer cells more effectively. This therapy has shown promise in treating relapsed or refractory acute lymphoblastic leukemia (ALL).
Do I need to stop my current medications for the trial?
Yes, you will need to stop certain medications before participating in the trial. Chemotherapy and biologic therapy must be stopped at least 7 days before collection, systemic corticosteroids 7 days prior, Tyrosine Kinase Inhibitors 3 days prior, and Hydroxyurea 1 day prior. Other specific medications have different requirements, so it's important to discuss your current medications with the trial team.
What data supports the effectiveness of the treatment CAR-T Cell Therapy for B-Cell Leukemia?
Research shows that CAR-T cell therapy targeting CD19 has led to complete remission in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia, which is significantly higher than the 30% response rate expected with traditional chemotherapy.
12345Is CAR-T cell therapy safe for humans?
CAR-T cell therapy has shown significant safety concerns, including severe toxicities like cytokine release syndrome (CRS) and neurotoxicity, which can be life-threatening. While it has been effective in treating B-cell leukemia, these side effects are a major challenge in its broader use.
678910What makes TriCAR T-cells treatment unique for B-cell leukemia?
TriCAR T-cells are a type of CAR-T cell therapy that involves genetically modifying a patient's own T-cells to better recognize and attack cancer cells. This treatment is unique because it targets specific markers on B-cell leukemia cells, potentially leading to higher remission rates compared to traditional chemotherapy.
14111213Eligibility Criteria
This trial is for young people aged 12 months to 21 years with B cell Acute Lymphoblastic Leukemia that's resistant or has returned. They must weigh at least 10 kg, have certain levels of liver and kidney function, a good heart function score, and be expected to live more than 8 weeks. Those who can get pregnant must agree to use effective birth control during the study.Inclusion Criteria
I am over 18 and can make my own health decisions or have a guardian who can.
I have stopped all cancer treatments and recovered from their major side effects.
I am between 12 and 21 years old and eligible for the TRICAR-ALL T cell infusion.
+5 more
Exclusion Criteria
Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol
I do not have any cancer other than the one being studied.
I have a brain condition that needs treatment.
+5 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Chemotherapy
Participants receive lymphodepletion chemotherapy with Cyclophosphamide for 2 days and Fludarabine for 4 days
6 days
Daily visits during chemotherapy
Treatment
Participants receive an infusion of TRICAR-ALL T-cells and are monitored for up to 3 hours post-infusion
1 day
1 visit (in-person)
Initial Follow-up
Participants are monitored for safety and effectiveness with regular visits and tests
4 weeks
Visits on days 1, 4, 7, 10, 14, 28 post-infusion
Extended Follow-up
Participants continue to be monitored for long-term safety and effectiveness
15 years
Visits at 3, 6, 12 months, then yearly
Participant Groups
The trial tests 'TRICAR-ALL' T-cells combined with lymphodepletion chemotherapy in patients with leukemia. These special T-cells are engineered in the lab to target cancer cells more effectively by using a modified antibody that sticks to three specific proteins on leukemia cells.
1Treatment groups
Experimental Treatment
Group I: Autologous TRICAR-ALL T-Cells and lymphodepletion chemotherapyExperimental Treatment1 Intervention
Three dose levels will be evaluated. The TRICAR-ALL T-cells will be administered after lymphodepletion chemotherapy with Cyclophosphamide and fludarabine.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Houston Methodist HospitalHouston, TX
Texas Children's HospitalHouston, TX
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Who Is Running the Clinical Trial?
Baylor College of MedicineLead Sponsor
Center for Cell and Gene Therapy, Baylor College of MedicineCollaborator
The Methodist Hospital Research InstituteCollaborator
Texas Children's Cancer CenterCollaborator
References
CD19-Targeted CAR T cells as novel cancer immunotherapy for relapsed or refractory B-cell acute lymphoblastic leukemia. [2023]Immunotherapy has demonstrated significant potential for the treatment of patients with chemotherapy-resistant hematologic malignancies and solid tumors. One type of immunotherapy involves the adoptive transfer of T cells that have been genetically modified with a chimeric antigen receptor (CAR) to target a tumor. These hybrid proteins are composed of the antigen-binding domains of an antibody fused to T-cell receptor signaling machinery. CAR T cells that target CD19 recently have made the jump from the laboratory to the clinic, and the results have been remarkable. CD19-targeted CAR T cells have induced complete remissions of disease in up to 90% of patients with relapsed or refractory B-cell acute lymphoblastic leukemia (B-ALL), who have an expected complete response rate of 30% in response to chemotherapy. The high efficacy of CAR T cells in B-ALL suggests that regulatory approval of this therapy for this routinely fatal leukemia is on the horizon. We review the preclinical development of CAR T cells and their early clinical application for lymphoma. We also provide a comprehensive analysis of the use of CAR T cells in patients with B-ALL. In addition, we discuss the unique toxicities associated with this therapy and the management schemes that have been developed.
Treatment of adult ALL patients with third-generation CD19-directed CAR T cells: results of a pivotal trial. [2023]Third-generation chimeric antigen receptor (CAR)-engineered T cells (CARTs) might improve clinical outcome of patients with B cell malignancies. This is the first report on a third-generation CART dose-escalating, phase-1/2 investigator-initiated trial treating adult patients with refractory and/or relapsed (r/r) acute lymphoblastic leukemia (ALL).
TCRαβ/CD3 disruption enables CD3-specific antileukemic T cell immunotherapy. [2022]T cells engineered to express chimeric antigen receptors (CARs) against B cell antigens are being investigated as cellular immunotherapies. Similar approaches designed to target T cell malignancies have been hampered by the critical issue of T-on-T cytotoxicity, whereby fratricide or self-destruction of healthy T cells prohibits cell product manufacture. To date, there have been no reports of T cells engineered to target the definitive T cell marker, CD3 (3CAR). Recent improvements in gene editing now provide access to efficient disruption of such molecules on T cells, and this has provided a route to generation of 3CAR, CD3-specific CAR T cells. T cells were transduced with a lentiviral vector incorporating an anti-CD3ε CAR derived from OKT3, either before or after TALEN-mediated disruption of the endogenous TCRαβ/CD3 complex. Only transduction after disrupting assembly of TCRαβ/CD3 yielded viable 3CAR T cells, and these cultures were found to undergo self-enrichment for 3CAR+TCR-CD3- T cells without any further processing. Specific cytotoxicity against CD3ε was demonstrated against primary T cells and against childhood T cell acute lymphoblastic leukemia (T-ALL). 3CAR T cells mediated potent antileukemic effects in a human/murine chimeric model, supporting the application of cellular immunotherapy strategies against T cell malignancies. 3CAR provides a bridging strategy to achieve T cell eradication and leukemic remission ahead of conditioned allogeneic stem cell transplantation.
Chimeric antigen receptor T-cell therapy for adult B-cell acute lymphoblastic leukemia: state-of-the-(C)ART and the road ahead. [2023]Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy has recently been added to the armamentarium in the battle against B-cell acute lymphoblastic leukemia (B-ALL). In this review, we discuss the trials that led to US Food and Drug Administration approval of CAR T-cell therapies in patients with B-ALL. We evaluate the evolving role of allogeneic hematopoietic stem cell transplant in the CAR T-cell era and discuss lessons learned from the first steps with CAR T-cell therapy in ALL. Upcoming innovations in CAR technology, including combined and alternative targets and off-the-shelf allogeneic CAR T-cell strategies are presented. Finally, we envision the role that CAR T cells could take in the management of adult patients with B-ALL in the near future.
Chimeric Antigen Receptor T-Cell Therapy Clinical Results in Pediatric and Young Adult B-ALL. [2020]Chimeric antigen receptor (CAR)-modified T-cell therapy has revolutionized the care of patients with relapsed and refractory B-cell acute lymphoblastic leukemia (B-ALL). Results from clinical trials across multiple institutions report remarkable remission rates with CD19-directed CAR-modified T-cell therapy. These remissions are also proving to be durable in many patients with a relapse-free survival (RFS) of approximately 50% to 60% at 1 year across several trials and institutions in this population that has been historically very difficult to treat. In addition, new products are being developed to enhance upon the original CAR T-cell products, which include a humanized CAR, allogeneic CARs, and both CD22 and biallelic CD19 and CD22 constructs. Toxicity after CAR-modified T-cell therapy is characterized by cytokine release syndrome (CRS) and neurotoxicity in the acute post-infusion period and B-cell aplasia as a long-term consequence of treatment. This review will summarize the published data thus far on the use of CAR-modified T-cell therapy in pediatric B-ALL and outline the various CAR products now being developed for this population. Delivery of this therapy and the decision to pursue hematopoietic stem cell transplant (HSCT) after treatment will be discussed.
Chimeric Antigen Receptor Therapy in Acute Lymphoblastic Leukemia Clinical Practice. [2018]Over half of patients diagnosed with B-cell acute lymphoblastic leukemia (ALL) develop relapsed or refractory disease. Traditional chemotherapy salvage is inadequate, and new therapies are needed. Chimeric antigen receptor (CAR) T cell therapy is a novel, immunologic approach where T cells are genetically engineered to express a CAR conferring specificity against a target cell surface antigen, most commonly the pan-B-cell marker CD19. After infusion, CAR T cells expand and persist, allowing ongoing tumor surveillance. Several anti-CD19 CAR T cell constructs have induced high response rates in heavily pre-treated populations, although durability of response varied. Severe toxicity (cytokine release syndrome and neurotoxicity) is the primary constraint to broad implementation of CAR T cell therapy. Here, we review the experience of CAR T cell therapy for ALL and ongoing efforts to modify existing technology to improve efficacy and decrease toxicity. As an anti-CD19 CAR T cell construct may be FDA approved soon, we focus on issues relevant to practicing clinicians.
Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant. [2021]Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.
CAR-T Cell Therapy: the Efficacy and Toxicity Balance. [2023]Chimeric antigen receptor (CAR) T cell therapy is an immunotherapy that has resulted in tremendous progress in the treatment of patients with B cell malignancies. However, the remarkable efficacy of therapy is not without significant safety concerns. Herein, we will review the unique and potentially life-threatening toxicities associated with CAR-T cell therapy and their association with treatment efficacy.
Effects of CAR-T Cell Therapy on Immune Cells and Related Toxic Side Effect Analysis in Patients with Refractory Acute Lymphoblastic Leukemia. [2023]To observe the effects of chimeric antigen receptor T (CAR-T) cell immunotherapy on immune cells and related toxic side effects in patients with refractory acute lymphoblastic leukemia (ALL).
CAR T-Cells for the Treatment of B-Cell Acute Lymphoblastic Leukemia. [2023]B-cell acute lymphoblastic leukemia (B-ALL) is the most common subtype of acute leukemia in the pediatric population. The prognosis and treatment of B-ALL have dramatically improved over the past decade with the adoption of intensive and prolonged combination chemotherapy regimens. The advent of novel immunologic agents such as blinatumomab and inotuzumab has changed the treatment landscape of B-ALL. However, patients have continued to relapse, raising the need for novel therapies. Chimeric antigen receptor (CAR) T-cells have achieved a milestone in the treatment of B-ALL. Two CD19-targeting CAR T-cells were approved by the Food and Drug Administration and the European Medicines Agency for the treatment of relapsed and/or refractory B-ALL. In this review, we review the available data regarding CD19-targeting CAR T-cells with their safety profile as well as the mechanism of resistance to these agents and the way to overcome this resistance.
Progress on CAR-T cell therapy for hematological malignancies. [2022]Chimeric antigen receptor (CAR) T cell therapy is an effective treatment for hematological malignancies, which have experienced the development of CD19 CAR-T cells for B lymphoblastic leukemia and lymphoma, B cell maturation antigen (BCMA) CAR-T cells for multiple myeloid, and more recently, the development of CD7 CAR-T cells for T cell malignancies. There are more obstacles for myeloid malignancies compared to other hematological malignancies in this field, thus concerning researches are in more diverse ways. In order to obtain more effective clinical CAR-T cells with lower side effects, scientists have developed multi-target CAR-T cells, universal CAR-T cells, as well as CAR-T cells, CAR-NK cells, CAR-iMac cells derived from induced pluripotent stem cells (iPSC) by genetic engineering. Chinese scientists have made significant contribution to the invention and manufacture of origin CAR-T cells and the establishment of an intact clinical research system. This review introduces the latest progress involving CAR-T cell therapy for hematological malignancies including B lymphoblastic malignancies, T lymphoblastic malignancies and myeloid malignancies, and also discuss the future developments including multi-target, universal and iPSC-derived CAR-related cell therapy.
CAR therapy for hematological cancers: can success seen in the treatment of B-cell acute lymphoblastic leukemia be applied to other hematological malignancies? [2018]Chimeric antigen receptor (CAR) T-cell therapy has recently come into the spotlight due to impressive results in patients with B-cell acute lymphoblastic leukemia. By targeting CD19, a marker expressed most B-cell tumors, as well as normal B cells, CAR T-cell therapy has been investigated as a treatment strategy for B-cell leukemia and lymphoma. This review will discuss the successes of this therapy for the treatment of B-cell acute lymphoblastic leukemia and the challenges to this therapeutic strategy. We will also discuss application of CAR T-cell therapy to chronic lymphocytic leukemia and other B-cell malignancies including a follicular lymphoma, diffuse large B-cell lymphoma, as well as acute and plasma cell malignancies.
CAR-T therapy as a consolidation in remission B-ALL patients with poor prognosis. [2022]To date, almost all studies regarding chimeric antigen receptor (CAR)-T cell therapy for B-cell acute lymphoblastic leukemia (B-ALL) were performed in refractory/relapsed (r/r) or minimal residual disease-positive patients. CAR-T therapy in remission patients has not been reported.