CAR T-Cell Therapy for Chronic Lymphocytic Leukemia
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
Sponsor: National Cancer Institute (NCI)
Must not be taking: Anticoagulants, Checkpoint inhibitors
Disqualifiers: HIV, Second malignancies, Uncontrolled infections, others
No Placebo Group
Breakthrough Therapy
Approved in 3 Jurisdictions
Trial Summary
What is the purpose of this trial?Background:
Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are blood cancers that affect certain white blood cells. Advanced forms of these diseases are difficult to treat. CD19 is a protein often found on the surfaces of these cancer cells. Researchers can modify a person's own immune cells (T cells) to target CD19. When these modified T cells are returned to the body-a treatment called anti-CD19 chimeric antigen receptor (CAR) T cell therapy-they may help kill cancer cells.
Objective:
To test anti-CD19 CAR T cell therapy in people with CLL or SLL.
Eligibility:
People aged 18 years and older with CLL or SLL that has not been controlled with standard drugs.
Design:
Participants will be screened. They will have imaging scans and tests of their heart function. If a sample of tissue from their tumor is not available, a new one may be taken; the sample will be tested for CD19.
Participants will receive a drug to reduce the leukemia cells in their blood. Then they will undergo apheresis: Blood will be taken from the body through a needle. The blood will pass through a machine that separates out the T cells. The remaining blood will be returned to the body through a different needle. The collected T cells will be gene edited to make them attack cells with CD19.
Participants will take drugs to prepare them for treatment for 3 days. These drugs will start 5 days before the treatment. Then their own modified CAR T cells will be returned to their bloodstream. Participants will stay in the hospital for at least 9 days after the treatment.
Follow-up visits will continue for 5 years.
Will I have to stop taking my current medications?
The trial requires that participants stop taking systemic corticosteroids greater than 5 mg/day of prednisone or equivalent at least 14 days before starting rituximab. Additionally, participants on systemic anticoagulant therapy, except aspirin, are not allowed.
What data supports the effectiveness of the treatment for Chronic Lymphocytic Leukemia?
The treatment, which involves CAR T cells targeting CD19, has shown effectiveness in treating other B-cell cancers like acute lymphoblastic leukemia and diffuse large B-cell lymphoma. These successes suggest potential benefits for similar B-cell malignancies, such as Chronic Lymphocytic Leukemia.
12345Is CAR T-cell therapy safe for humans?
CAR T-cell therapy, including treatments like tisagenlecleucel (Kymriah), has been associated with serious but mostly reversible side effects, such as cytokine release syndrome (a severe immune reaction) and neurotoxicity (effects on the nervous system). Medium-term complications can include low blood cell counts and B-cell aplasia (a lack of B cells, which are part of the immune system).
12456How is CAR T-cell therapy for chronic lymphocytic leukemia different from other treatments?
CAR T-cell therapy for chronic lymphocytic leukemia is unique because it uses the patient's own T cells, which are modified to target and destroy cancer cells expressing the CD19 protein. This personalized approach is different from standard treatments like chemotherapy or kinase inhibitors, which are not specifically tailored to target cancer cells in this way.
578910Eligibility Criteria
This trial is for adults over 18 with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) that hasn't responded to standard treatments. Participants must have a tumor sample available for CD19 testing, and their heart and overall health should be stable enough to undergo the procedures involved in the trial.Inclusion Criteria
I've had at least two treatments for my condition, including one with a BTK inhibitor.
I am fully active or can carry out light work.
My heart pumps blood effectively.
+15 more
Exclusion Criteria
I have an active condition where my red blood cells are being destroyed faster than they can be made.
I have had a stem cell transplant from a donor.
I need urgent treatment because my tumor is pressing on my spine or other organs.
+20 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Pre-treatment
Participants receive a drug to reduce leukemia cells and undergo apheresis to collect T cells
1 week
1 visit (in-person)
Conditioning Chemotherapy
Participants receive rituximab and a lymphocyte-depleting chemotherapy regimen
3 days
3 visits (in-person)
CAR T-cell Infusion
Participants receive an infusion of genetically modified CAR T cells
1 day
1 visit (in-person)
Inpatient Monitoring
Participants are monitored for toxicity in the hospital
9 days
Inpatient stay
Follow-up
Participants are monitored for safety and effectiveness after treatment
5 years
Regular visits (in-person and virtual)
Participant Groups
The study tests anti-CD19 CAR T cell therapy, where patients' own immune cells are modified to target cancer cells. It involves taking medication to reduce leukemia cells, extracting T cells from blood, genetically modifying them in a lab, and then infusing them back into the patient's bloodstream.
2Treatment groups
Experimental Treatment
Group I: 2/Rituximab, conditioning chemotherapy plus CAR T-cells- Dose expansionExperimental Treatment4 Interventions
MTD dose or Optimal dose of Anti-CD19 CAR T- cells/kg + rituximab and conditioning chemotherapy
Group II: 1/Rituximab, conditioning chemotherapy plus CAR T-cells- Dose escalationExperimental Treatment4 Interventions
Escalating dose of anti-CD19 CAR T- cells/kg + rituximab and conditioning chemotherapy
Autologous HuCD19 (Anti-CD19) CAR T cells is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Kymriah for:
- B-cell precursor acute lymphoblastic leukemia (ALL)
- Relapsed or refractory large B-cell lymphoma
- Relapsed or refractory follicular lymphoma
🇪🇺 Approved in European Union as Kymriah for:
- B-cell precursor acute lymphoblastic leukemia (ALL)
- Relapsed or refractory large B-cell lymphoma
- Relapsed or refractory follicular lymphoma
🇨🇦 Approved in Canada as Kymriah for:
- B-cell precursor acute lymphoblastic leukemia (ALL)
- Relapsed or refractory large B-cell lymphoma
- Relapsed or refractory follicular lymphoma
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
[Medium-term follow-up of patients treated with chimeric antigen receptor T cells (CAR T cells): Recommendations of the Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC)]. [2022]Chimeric antigen receptor (CAR) T cells are a new class of anti-cancer therapy that involves manipulating autologous or allogeneic T cells to express a CAR directed against a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) has marketing authorization for the treatment of relapsed / refractory acute lymphoblastic leukemia (ALL) in children and young adults, in addition to the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL); the marketing authorization for axicabtagene ciloleucel (Yescarta™) is for the treatment of relapsed / refractory high-grade B-cell lymphoma and for the treatment of primary mediastinal B-cell lymphoma. Both cell products are genetically modified autologous T cells directed against CD19. These recommendations, drawn up by a working group of the Francophone Society of Bone Marrow transplantation and cellular Therapy (SFGM-TC) relate to the management of patients and the supply chain: medium-term complications, in particular cytopenias and B-cell aplasia, nursing and psychological supportive care. In another work, we will address long-term monitoring, post-marketing authorization pharmacovigilance and issues relating to JACIE and regulatory authorities. These recommendations are not prescriptive; their aim is to provide guidelines for the use of this new therapeutic approach. The purpose of this workshop is to outline the organizational aspects of this new therapeutic approach.
CAR T Cell Toxicity: Current Management and Future Directions. [2020]By late 2018, 2 chimeric antigen receptor T (CAR T) cell products have been approved by US and European regulatory authorities. Tisagenlecleucel (Kymriah, Novartis) is indicated in the treatment of patients up to 25 years of age with B-cell acute lymphoblastic leukemia (ALL) that is refractory or in second or later relapse, or adult patients with large B-cell lymphoma relapsed or refractory (r/r) after 2 or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified, high grade B-cell lymphoma and DLBCL arising from follicular lymphoma. Axicabtagene ciloleucel (Yescarta, Kite) is indicated for the treatment of adult patients with large B-cell lymphoma relapsed or refractory after 2 or more lines of systemic therapy, including DLBCL not otherwise specified, primary mediastinal large B-cell lymphoma, high grade B-cell lymphoma, and DLBCL arising from follicular lymphoma (ZUMA-1 trial). This review will offer a practical guide for the recognition and management of the most important toxicities related to the use of the current commercial CAR T cells, and also highlight strategies to diminish these side effects in the future.
[How to perform leukapheresis for procurement of the staring material used for commercial CAR T-cell manufacturing: A consensus from experts convened by the SFGM-TC]. [2021]Chimeric antigen receptor (CAR) T-cells are a new class of cancer treatments manufactured through autologous or allogeneic T cells genetic engineering to induce CAR expression directed against a membrane antigen present at the surface of malignant cells. In Europe, tisagenlecleucel (Kymriah™) has a marketing authorization for the treatment of relapsed/refractory B-cell acute lymphoblastic leukemia in children and young adults and for the relapsed/refractory diffuse large B-cell lymphoma (DLBCL). The marketing authorization for axicabtagene ciloleucel (Yescarta™) is the treatment of relapsed/refractory DLBCL and mediastinal B-cell lymphoma. Both products are "living drugs" and genetically modified autologous T cells directed against CD19 which is an antigen expressed throughout B lymphoid differentiation and on many B malignancies. This collaborative work - part of a series of expert works on the topic - aims to provide practical advice to assist collection facilities that procure the starting material i.e. blood mononuclear cells for autologous CAR T-cell manufacturing.
Management of adults and children undergoing chimeric antigen receptor T-cell therapy: best practice recommendations of the European Society for Blood and Marrow Transplantation (EBMT) and the Joint Accreditation Committee of ISCT and EBMT (JACIE). [2022]Chimeric antigen receptor (CAR) T cells are a novel class of anti-cancer therapy in which autologous or allogeneic T cells are engineered to express a CAR targeting a membrane antigen. In Europe, tisagenlecleucel (Kymriah™) is approved for the treatment of refractory/relapsed acute lymphoblastic leukemia in children and young adults as well as relapsed/refractory diffuse large B-cell lymphoma, while axicabtagene ciloleucel (Yescarta™) is approved for the treatment of relapsed/refractory high-grade B-cell lymphoma and primary mediastinal B-cell lymphoma. Both agents are genetically engineered autologous T cells targeting CD19. These practical recommendations, prepared under the auspices of the European Society of Blood and Marrow Transplantation, relate to patient care and supply chain management under the following headings: patient eligibility, screening laboratory tests and imaging and work-up prior to leukapheresis, how to perform leukapheresis, bridging therapy, lymphodepleting conditioning, product receipt and thawing, infusion of CAR T cells, short-term complications including cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome, antibiotic prophylaxis, medium-term complications including cytopenias and B-cell aplasia, nursing and psychological support for patients, long-term follow-up, post-authorization safety surveillance, and regulatory issues. These recommendations are not prescriptive and are intended as guidance in the use of this novel therapeutic class.
[Chimeric antigen receptor T-cell therapy for hematological malignancies]. [2019]The adoptive transfer of chimeric antigen receptor (CAR)-modified autologous T cells targeted at the B-cell antigen CD19 is highly effective in patients with relapsed or refractory B-cell malignancies. In Japan, tisagenlecleucel has been approved in March 2019, whereas axicabtagene ciloleucel, lisocabtagene maraleucel, and TBI-1501 have been tested in clinical trials. In addition, allogeneic CD19 CAR T cells from family or third-party donors have been developed for treating B-cell malignancies. Moreover, CAR T-cell therapies for acute myeloid leukemia (AML), T-cell leukemia, and multiple myeloma are still under development. Our group is currently preparing a phase I study on granulocyte macrophage colony-stimulating factor receptor-targeted CAR T cells in pediatric and adult patients with AML.
Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. [2022]In a single-center phase 1-2a study, the anti-CD19 chimeric antigen receptor (CAR) T-cell therapy tisagenlecleucel produced high rates of complete remission and was associated with serious but mainly reversible toxic effects in children and young adults with relapsed or refractory B-cell acute lymphoblastic leukemia (ALL).
Tisagenlecleucel-T for the treatment of acute lymphocytic leukemia. [2019]Label="INTRODUCTION">Cellular immunotherapy with autologous or allogeneic T cells, genetically engineered to express chimeric antigen receptors (CARs) or T-cell receptors, in order to redirect their cytotoxic specificity toward malignant cells, is emerging as a promising new treatment modality. The most advanced approach in clinical development is the use of anti-CD19 CAR T-cells for the treatment of CD19+ B-cell malignancies, including acute lymphocytic leukemia (ALL). Areas covered: Recently, the Food and Drug Administration (FDA) approved the first anti-CD19 CAR T-cell product, tisagenlecleucel, for the treatment of pediatric and young adult patients with relapsed/refractory ALL. In this overview, we described the advances in the field, including a summary of clinical trials with tisagenlecleucel in ALL published to date. Expert opinion: CAR T-cell therapy has been developed in the context of small clinical studies and very few centers have had to deal with the challenges of managing CAR T-cells administration. However, this approach is likely to become a standard option for patients with relapsed/refractory B-cell lineage ALL.
Combination of Deauville score and quantitative positron emission tomography parameters as a predictive tool of anti-CD19 chimeric antigen receptor T-cell efficacy. [2023]Autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy is an effective treatment for approximately 40% of relapsed/refractory large B cell lymphomas (LBCL), and early identification of patients at risk for relapse or progression after CAR T-cell therapy represents a clinical need.
Safety and tolerability of conditioning chemotherapy followed by CD19-targeted CAR T cells for relapsed/refractory CLL. [2021]Subgroups of patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) exhibit suboptimal outcomes after standard therapies, including oral kinase inhibitors. We and others have previously reported on safety and efficacy of autologous CD19-targeted CAR T-cells for these patients; here we report safety and long-term follow-up of CAR T-cell therapy with or without conditioning chemotherapy for patients with R/R CLL and indolent B-cell non-Hodgkin lymphoma (B-NHL).
Long-Term Outcomes From a Randomized Dose Optimization Study of Chimeric Antigen Receptor Modified T Cells in Relapsed Chronic Lymphocytic Leukemia. [2021]To describe long-term outcomes of anti-CD19 chimeric antigen receptor T (CART) cells in patients with relapsed or refractory chronic lymphocytic leukemia (CLL).