Clinical trial recruitment for BALL CAR T-Cell therapy

16th March 2023: The treatment of cancer is being revolutionized by new immunotherapeutic drugs that target the microenvironment at the tumour site. T cells with chimeric antigen receptors (CAR) are being extensively researched for cancer immunotherapy. Tisagenlecleucel, a type of CD19-specific CAR-T cell, has just received clinical approval. CAR designs targeted at novel targets involved in haematological and solid malignancies are being tested in ongoing clinical trials. Simultaneous and sequential CAR-T cells are also being investigated for potential clinical uses, in addition to single-target CAR-T cell experiments. Clinical trials for CAR-engineered T cells with several targets are also starting.

The development of CAR-T cells is moving forward with the use of universal and T cell receptor-engineered CAR-T cells. In this study, we registered clinical trials of CAR-T cells in China, assessed the properties of CAR constructions, and gave a brief overview of the CAR-T study environment in China.

Landscape of CAR T-Cell therapy in China has grown at a very rapid pace in last few years. Recruitment for CAR T-Cell therapy clinical trials are ongoing at some of the leading cancer centers in China. Listed are some of the centers in China that are undertaking these clinical trials:

1. Tianjin Hematology Hospital（Legend Bio）
2. Anhui Provincial Hospital（Cells: Bioheng）
3. Peking University Hospital, Shenzhen （Cells: Bioheng）
4. The 1st Affiliated Hospital of Soochow University（Unicar-Therapy）
5. The 3rd Xiangya Hospital of Central South University（Unicar-Therapy）

Intervention / Treatment : CD19-targeted Chimeric Antigen Receptor (CAR) T Cells

Detailed description:

Dose exploration for this study will be a 3+3 design with a target DLT rate of <1/3. Dose exploration can be discontinued once one or more dose levels with an acceptable safety profile and satisfactory antitumor activity have been selected for subsequent evaluation. The maximum tolerated dose (MTD) may not be achieved at the dose levels predetermined in this study, as described below.

During the treatment period of the study, four dose levels of JWCAR029 will be evaluated. enrollment will begin at dose level 1, follow a 3+3 dose exploration design protocol, and finally select one or more dose levels with an acceptable safety profile and good antitumor activity as the recommended dose, after which dose exploration will be discontinued.

Dose limiting toxicity (DLT) will be evaluated within 28 days after JWCAR029 infusion. Each dose cohort is planned to enroll three subjects initially, and at least one pediatric subject younger than 10 years of age who can be evaluated for DLT will be enrolled at each dose level. In the first dose cohort, the first 3 subjects will be infused at least 14 days apart. At each higher dose level, the first 3 patients within the dose cohort will be treated at least 7 days apart. For dose levels considered safe, at least 3 subjects with assessable DLT must complete a 28-day DLT assessment period.

Inclusion Criteria:

1. Age ≤ 30 years and weight ≥10kg.
2. Patients with r/r B-ALL, defined as morphological disease in the bone marrow(≥5% blasts) and either of the following:
   • ≥2 BM relapse;
   • Refractory defined as relapse if first remission<12 months or not achieving a CR after 1 cycle of a standard induction chemotherapy regimen for relapsed leukemia;primary chemo-refractory as defined by not achieving a CR after 1 cycle of a conventional chemotherapy or 2 cycles of a standard induction chemotherapy regimen for relapsed leukemia;
   • Any BM relapse after HSCT which must be ≥90 days from HSCT at the time of screening, and be required to be free from GVHD and end from any immunosuppressive therapy ≥1 month at the time of screening;
   • Patients with Ph+ ALL are eligible if they are intolerant to or have failed two lines of TKI therapy, or if TKI therapy is contraindicated.
   Note: Patients with MRD+ after bridging therapy will be allowed for treatment.
3. Karnofsky (age ≥16 years) or Lansky (age <16 years) performance status >60.
4. Adequate organ function.
5. Vascular access is sufficient for leukocyte isolation.
6. Expected survival time > 3 months.
7. Any non-hematological toxicity due to previous treatment, except for alopecia and peripheral neuropathy, must be restored to ≤ grade 1.
8. Females of childbearing potential (all female subjects who are physiologically capable of becoming pregnant) must agree to use a highly effective method of contraception for 1 year following JWCAR029 infusion; male subjects whose partners are of childbearing potential must agree to use an effective barrier method of contraception for 1 year following JWCAR029 infusion.

Exclusion Criteria:

1. People with leukemia in the central nervous system (CNS) who have active CNS lesions and significant neurodegenerative symptoms, or people whose CNS grade is between CNS-2 and CNS-3 according to NCCN guidelines (people whose CNS grade is CNS-2 because of a puncture injury may be enrolled).
2. Existing or previous clinically significant CNS lesions such as epilepsy, epileptic seizures, paralysis, aphasia, cerebral edema, stroke, severe brain injury, dementia, Parkinson’s disease, cerebellar disease, organic brain syndrome, psychosis, etc.
3. Patients with genetic syndromes other than Down syndrome.
4. Patients with Burkitt’s lymphoma.
5. History of malignancy other than B-ALL for at least 2 years prior to enrollment.
6. The subject had an HBV, HCV, HIV or syphilis infection at the time of screening.
7. Subject has deep vein thrombosis (DVT) (cancer thrombosis or thrombosis) or pulmonary artery embolism (PE) or is on anticoagulation therapy for DVT or PE within 3 months prior to signing the informed consent form
8. uncontrolled systemic fungal, bacterial, viral or other infections.
9. Combination of active autoimmune diseases requiring immunosuppressive therapy.
10. Acute or chronic graft-versus-host disease.
11. History of any of the following cardiovascular diseases within the past 6 months: Class III or IV heart failure as defined by the New York Heart Association (NYHA), cardiac angioplasty or stenting, myocardial infarction, unstable angina, or other clinically significant heart disease.
12. Women who are pregnant or lactating. Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to initiation of lymphocyte clearance chemotherapy.
13. Previous treatment with CAR-T cells or other gene-modified T cells.
14. Previous anti-CD19/anti-CD3 therapy, or any other anti-CD19 therapy.
15. Relevant medications or treatments within a specified time frame.
16. the existence of any factors that, in the investigator’s opinion, may make it difficult or impossible for a subject to follow the protocol, such as uncontrollable medical, psychological, familial, sociological, or geographic circumstances, as well as an unwillingness or inability to do so.
17. Known life-threatening allergic reactions, hypersensitivity reactions, or intolerance to JWCAR029 cell formulation or its excipients.

Disclaimer

A study’s listing on this website does not imply that the authorities have reviewed it. The safety and scientific validity of a study listed here is the responsibility of the study sponsor and investigators. Know the risks and potential benefits of clinical studies, and talk to your health care provider before participating.

Study sponsors and investigators are in charge of ensuring that the studies adhere to all relevant laws and regulations and provide information on the website. NLM staff do not verify the scientific validity or relevance of the submitted information beyond a limited quality control review for apparent errors, deficiencies, or inconsistencies.

Choosing to participate in a study is an important personal decision. Before you participate in a study, discuss all options with your health care provider and other trusted advisors. For more information about participating in clinical studies, see Learn About Clinical Studies, which includes questions that you might want to ask before deciding to participate in a study.