Stem Cell + CAR T-Cell Therapy for Blood Cancers
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Joshua Sasine, MD, PhD
Must not be taking: Corticosteroids, Immunosuppressive drugs
Disqualifiers: Uncontrolled infection, Cardiac disease, Seizure disorder, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?
The study is designed to examine the feasibility and safety of collecting autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy for patients with relapsed/refractory (r/r) hematological disease. The study will evaluate feasibility of collecting the target dose of HSCs from at least 50% of enrolled patients. The study will assess safety based on incidence and severity of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in the first 60 days post CAR T dosing, and also through the collection of adverse events (AEs) and serious adverse events (SAEs) as well as the durability of response after treatment with HSCs with CAR T. The study follows an open-label, single-center and single non-randomized cohort design. 20 subjects with r/r hematological malignancies will be enrolled and treated to evaluate the feasibility and preliminary safety of collecting autologous HSCs and combining them with CAR T-cell therapy.
Will I have to stop taking my current medications?
The trial requires that you stop taking corticosteroids and other immunosuppressive drugs at doses of 5 mg/day or more of prednisone (a type of steroid) or equivalent. There is a washout period (time without taking certain medications) of 10 days before leukapheresis (a procedure to collect blood cells) and 10 days before receiving CAR T-cell therapy.
What data supports the effectiveness of the treatment Stem Cell + CAR T-Cell Therapy for Blood Cancers?
Research shows that CAR T-cell therapy, which is part of this treatment, has been effective in treating blood cancers like B-cell malignancies by targeting specific cancer cells. Studies have demonstrated that CAR T-cells can lead to long-term remission in patients with advanced blood cancers, even when other treatments have failed.12345
Is Stem Cell + CAR T-Cell Therapy generally safe for humans?
CAR T-Cell therapy, including products like Kymriah, has shown promise in treating blood cancers but can cause serious side effects. Common issues include cytokine release syndrome (a severe immune reaction), neurological problems, and blood cell deficiencies. While these therapies are advancing, managing these side effects is crucial for safe treatment.678910
What makes the Stem Cell + CAR T-Cell Therapy unique for blood cancers?
This treatment is unique because it combines autologous hematopoietic stem cells (patient's own stem cells) with CAR T-cell therapy, which uses modified T-cells to specifically target and attack cancer cells. This approach is particularly promising for patients with blood cancers where other treatments have failed, offering a personalized and powerful immunotherapy option.13111213
Research Team
JS
Joshua Sasine, MD, PhD
Principal Investigator
Cedars-Sinai Medical Center
Eligibility Criteria
Adults aged 18-85 with certain blood cancers that have come back or haven't responded to treatment can join. They must be healthy enough for the procedure, not have had recent heart issues or transplants, and can't be pregnant or breastfeeding. Participants need to agree to birth control use and follow study procedures.Inclusion Criteria
Women who can have children must take a pregnancy test before the study starts.
My condition worsened after the last treatment or didn't improve significantly.
It's been over 2 weeks or 5 half-lives since my last cancer treatment.
See 8 more
Exclusion Criteria
I currently have or might have an infection that isn't under control or needs IV drugs.
Any medical condition likely to interfere with assessment of feasibility or safety of study treatment
I have not received a live vaccine in the last 6 weeks.
See 10 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Collection and Preparation
Collection of autologous hematopoietic stem cells (HSCs) to be combined with CAR T-cell therapy
Up to 10 days
Multiple visits for collection and preparation
Treatment
Participants receive CAR T-cell therapy and are monitored for safety, including incidence of CRS and ICANS
60 days
Regular monitoring visits
Follow-up
Participants are monitored for safety and effectiveness after treatment, including response rate and recovery assessments
52 weeks
Periodic follow-up visits
Long-term Follow-up
Assessment of progression-free survival (PFS) and overall survival (OS) for up to 3 years
Up to 3 years
Treatment Details
Interventions
- Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy (CAR T-cell Therapy)
Trial OverviewThe trial is testing if it's possible and safe to collect a person's own stem cells and add them to CAR T-cell therapy in patients whose blood cancer has returned after treatment or hasn’t improved. It will track how well this works in 20 people over the first two months by looking at side effects like CRS and ICANS.
Participant Groups
1Treatment groups
Experimental Treatment
Group I: CAR T Therapy with Autologous Hematopoietic Stem Cells (aHSCs)Experimental Treatment1 Intervention
Autologous Hematopoietic Stem Cells with Chimeric Antigen Receptor (CAR) T-Cell Therapy is already approved in European Union, United States for the following indications:
🇪🇺 Approved in European Union as Kymriah for:
- B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years of age
- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy
🇺🇸 Approved in United States as Kymriah for:
- B-cell acute lymphoblastic leukemia (ALL) in patients up to 25 years of age
- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) after two or more lines of systemic therapy
- Relapsed or refractory follicular lymphoma after two or more lines of systemic therapy
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Cedars-Sinai Medical CenterLos Angeles, CA
Loading ...
Who Is Running the Clinical Trial?
Joshua Sasine, MD, PhD
Lead Sponsor
Trials
1
Patients Recruited
20+
References
Adoptive Immunotherapy for B-cell Malignancies Using CD19- Targeted Chimeric Antigen Receptor T-Cells: A Systematic Review of Efficacy and Safety. [2019]Adoptive infusion of chimeric antigen receptor transduced T- cells (CAR-T) is a powerful tool of immunotherapy for hematological malignancies, as evidenced by recently published and unpublished clinical results.
Adoptive T-cell therapy of B-cell malignancies: conventional and physiological chimeric antigen receptors. [2020]Hematological malignancies remain incurable diseases because of the high risk of relapse, even after complete remission. Adoptive T-cell therapy (ACT) using modified T cells with chimeric antigen receptors (CARs) targeted to specific tumor-associated antigens expressed by B-cell malignancies represents an attractive approach for cancer immunotherapy. Investigators optimized the design of CARs to enhance receptor mediated T cell signaling and demonstrated that second and third generation CARs, including various costimulatory molecules, resulted in enhanced T-cell persistence and sustained antitumor activity in both in vitro and in vivo mouse models as well as clinical trials. We highlight advances in the use of CARs in the treatment of B-cell malignancies and future challenges in the use of adoptive therapy with CAR-engineered T cells.
Practical aspects of CAR-T cell therapy. [2022]Chimeric antigen receptor (CAR) T cell therapy has been gradually building its position in the treatment of hematological malignancies. Currently, there are three types of autologous anti-CD19 CAR-T cells approved for the treatment of selected relapsed B cell non-Hodgkins lymphomas and acute B-lymphoblastic leukemia in the Czech Republic. Additional clinical trials are ongoing to evaluate CAR-T cell therapy that targets other tumor-specific antigens. It is expected that some of these CAR-T cells will be approved for the treatment of other hemato-oncological dia-gnoses in the near future. Manufacturing and management of CAR-T cell therapy have been optimized. European Society for Blood and Marrow Transplantation and American Society for Transplantation and Cellular Therapy have updated their recommendations for the management and treatment of early CAR-T cell toxicity based on valuable experience gained during several years. Nevertheless, late toxicity remains an issue. It is crucial for patients undergoing this highly specific therapy to stay in follow-up for several decades. Intensive research and development have been devoted to manufacturing new CAR constructs with higher efficacy and lesser toxicity. A significant improvement in the availability of this, otherwise very expensive treatment, is expected from universal allogeneic T cells that will express CAR binding to tumor-specific antigen.
Chimeric Antigen Receptor T Cell Therapy versus Hematopoietic Stem Cell Transplantation: An Evolving Perspective. [2023]Cellular therapy modalities, including autologous (auto-) hematopoietic cell transplantation (HCT), allogeneic (allo-) HCT, and now chimeric antigen receptor (CAR) T cell therapy, have demonstrated long-term remission in advanced hematologic malignancies. Auto-HCT and allo-HCT, through hematopoietic rescue, have permitted the use of higher doses of chemotherapy. Allo-HCT also introduced a nonspecific immune-mediated targeting of malignancy resulting in protection from relapse, although at the expense of similar targeting of normal host cells. In contrast, CAR T therapy, through genetically engineered immunotherapeutic precision, allows for redirection of autologous immune effector cells against malignancy in an antigen-specific and MHC-independent fashion, with demonstrated efficacy in patients who are refractory to cytotoxic chemotherapy. It too has unique toxicities and challenges, however. Non-Hodgkin lymphoma (including large B cell lymphoma, mantle cell lymphoma, and follicular lymphoma), B cell acute lymphoblastic leukemia, and multiple myeloma are the 3 main diseases associated with the use of fully developed CAR T products with widespread deployment. Recent and ongoing clinical trials have been examining the interface among the 3 cellular therapy modalities (auto-HCT, allo-HCT, and CAR T) to determine whether they should be "complementary" or "competitive" therapies. In this review, we examine the current state of this interface with respect to the most recent data and delve into the controversies and conclusions that may inform clinical decision making.
Chimeric antigen receptor T cell treatment in hematologic malignancies. [2017]Adoptive transfer of T cells that have genetically engineered chimeric antigen receptors (CARs) is an encouraging treatment modality in the hematological malignancies. These T cells are capable of selectively recognizing tumor-associated antigens. There are a variety of reported, as well as ongoing studies on the utilization of CAR-T cells in the treatment of leukemia, myeloma, as well as B and T cell lymphomas. In this review, we aimed to highlight current understanding of this promising treatment modality, including its efficacy and adverse effects.
Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in patients with haematological and solid malignancies: protocol for a systematic review and meta-analysis. [2019]Patients with relapsed or refractory malignancies have a poor prognosis. Immunotherapy with chimeric antigen receptor T (CAR-T) cells redirects a patient's immune cells against the tumour antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies, including acute B-cell lymphoblastic leukaemia and B-cell lymphomas. CAR-T cell therapy for patients with other solid tumours is also being tested. Safety is an important consideration in CAR-T cell therapy given the potential for serious adverse events, including death. Previous reviews on CAR-T cell therapy have been limited in scope and methodology. Herein, we present a protocol for a systematic review to identify CAR-T cell interventional studies and examine the safety and efficacy of this therapy in patients with haematology malignancies and solid tumours.
Current status and perspective of CAR-T and CAR-NK cell therapy trials in Germany. [2023]Chimeric antigen receptor (CAR)-T cell therapies are on the verge of becoming powerful immunotherapeutic tools for combating hematological diseases confronted with pressing medical needs. Lately, CAR-NK cell therapies have also come into focus as novel therapeutic options to address hurdles related to CAR-T cell therapies, such as therapy-induced side effects. Currently, more than 500 CAR-T and 17 CAR-NK cell trials are being conducted worldwide including the four CAR-T cell products Kymriah, Yescarta, Tecartus and Breyanzi, which are already available on the market. Most CAR-T cell-based gene therapy products that are under clinical evaluation consist of autologous enriched T cells, whereas CAR-NK cell-based approaches can be generated from allogeneic donors. Besides modification based on a second-generation CAR, more advanced CAR-immune cell therapeutics are being tested, which utilize precise insertion of genes to circumvent graft-versus-host disease (GvHD) or employ a dual targeting approach and adapter CARs in order to avoid therapy resistance caused by antigen loss. In this review, we are going to take a closer look at the commercial CAR-T cell therapies, as well as on CAR-T and CAR-NK cell products, which are currently under evaluation in clinical trials, that are being conducted in Germany.
Toxicity and management in CAR T-cell therapy. [2023]T cells can be genetically modified to target tumors through the expression of a chimeric antigen receptor (CAR). Most notably, CAR T cells have demonstrated clinical efficacy in hematologic malignancies with more modest responses when targeting solid tumors. However, CAR T cells also have the capacity to elicit expected and unexpected toxicities including: cytokine release syndrome, neurologic toxicity, "on target/off tumor" recognition, and anaphylaxis. Theoretical toxicities including clonal expansion secondary to insertional oncogenesis, graft versus host disease, and off-target antigen recognition have not been clinically evident. Abrogating toxicity has become a critical step in the successful application of this emerging technology. To this end, we review the reported and theoretical toxicities of CAR T cells and their management.
Adverse effects in hematologic malignancies treated with chimeric antigen receptor (CAR) T cell therapy: a systematic review and Meta-analysis. [2022]Recently, chimeric antigen receptor-modified (CAR) T cell therapy for hematological malignancies has shown clinical efficacy. Hundreds of clinical trials have been registered and lots of studies have shown hematologic toxic effects were very common. The main purpose of this review is to systematically analyze hematologic toxicity in hematologic malignancies treated with CAR-T cell therapy.
CAR-T-OPENIA: Chimeric antigen receptor T-cell therapy-associated cytopenias. [2022]Chimeric antigen receptor (CAR) T-cell is the most recent version in the evolution of cellular therapy with promising responses, which has revolutionized the management of some hematological malignancies in the current times. As the clinical use has progressed rather rapidly since the first approval in 2017, toxicities beyond cytokine release syndrome and immune effector cell-associated neurological syndrome have surfaced. Cytopenias are common in 90 days ("prolonged"); and have clinical implications to patient care as well as resource utilization. We review the details of etiology, factors associated with cytopenias, and management considerations for patients with cytopenias for each of these time-frames. This would potentially serve as a clinical guide for hematological toxicity or CAR-T-OPENIA, which is commonly encountered with the use of CAR T-cell therapy.
Identifying and managing CAR T-cell-mediated toxicities: on behalf of an Italian CAR-T multidisciplinary team. [2022]Chimeric antigen receptor (CAR)-T-cell therapy is a new treatment for patients with hematologic malignancies in which other therapies have failed.
Adoptive immunotherapy for hematological malignancies: Current status and new insights in chimeric antigen receptor T cells. [2018]Hematological malignancies frequently express cancer-associated antigens that are shared with normal cells. Such tumor cells elude the host immune system because several T cells targeted against self-antigens are removed during thymic development, and those that persist are eliminated by a regulatory population of T cells. Chimeric antigen receptor-modified T cells (CAR-Ts) have emerged as a novel modality for tumor immunotherapy due to their powerful efficacy against tumor cells. These cells are created by transducing genes-coding fusion proteins of tumor antigen-recognition single-chain Fv connected to the intracellular signaling domains of T cell receptors, and are classed as first-, second- and third-generation, differing on the intracellular signaling domain number of T cell receptors. CAR-T treatment has emerged as a promising approach for patients with hematological malignancies, and there are several works reporting clinical trials of the use of CAR-modified T-cells in acute lymphoblastic leukemia, chronic lymphoblastic leukemia, multiple myeloma, lymphoma, and in acute myeloid leukemia by targeting different antigens. This review reports the history of adoptive immunotherapy using CAR-Ts, the CAR-T manufacturing process, and T cell therapies in development for hematological malignancies.
Risk of infection in patients with hematological malignancies receiving CAR T-cell therapy: systematic review and meta-analysis. [2022]Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising treatment option for relapsed or refractory B-cell malignancies and multiple myeloma. Underlying and treatment-related variables may contribute to the development of infectious complications.