Shanxi Bethune Hospital Evaluating CAR-T for R/R Hematological Tumors in Phase 2/3 Clinical Trial

Shanxi Bethune Hospital, located in China’s Shanxi province, is currently evaluating a chimeric antigen receptor T-cell (CAR-T) therapy for the treatment of relapsed/refractory (r/r) hematological tumors in a phase 2/3 clinical trial (NCT06238336).

The single-center, open-label, study aims to assess the safety and efficacy of the CAR-T therapy. Participants undergo nonmyeloablative chemotherapy prior to treatment with the CAR-T. The study follows a dose climbing format, with a starting dose of 1.0x10⁶ cells of the CAR-T per kg, and 3 patients per dose group. Additional dose levels listed by the investigators are 2.0x10⁶ cells/kg and 4.0x10⁶ cells/kg.

According to the clinicaltrials.gov page for the study, which was most recently updated on February 2, 2024, the study is currently recruiting at Shanxi Bethune Hospital in Taiyuan. The trial, which has an estimated primary completion date of November 15, 2025, and an estimated completion date of December 20, 2025, began on June 15, 2020. It is expected to enroll approximately 30 participants in total.

The trial’s primary end point is the incidence of treatment-related adverse events in the period of up to 36 months posttreatment, along with serious adverse events and clinically significant laboratory abnormalities. Secondary endpoints pertain to efficacy and include measures of CART-cell expansion, CART-cell persistence, lymphocyte ablation characteristics, the objective response rate (ORR), the progression-free survival, andthe event-free survival. All secondary end points, excepting ORR, are noted to be assessed in a time frame of up to 36 months. The ORR, on the other hand, is noted to be assessed at 3 months, 6 months, and 1 year posttreatment. It is noted that CAR T-cell expansion and persistence will be assessed in the peripheral blood, bone marrow, cerebrospinal fluid, and lymph nodes.

The study is open to patients aged between 14 and 70 years old, with a confirmed malignant hematological tumor and measurable or evaluable lesions. Patients must also have adequate liver, kidney, lung, and cardiac function, adequate peripheral superficial venous blood flow, an Eastern Cooperative Oncology Group performance status of 2 or lower, and an expected survival time of at least 3 months. Patients are excluded if they are pregnant or breastfeeding, have any uncontrolled infections within 4 weeks before enrollment, have active viral hepatitis B or hepatitis C, or have an HIV infection. Patients who have severe autoimmune diseases or immunodeficiency disorders, are allergic to large molecule biopharmaceuticals (e.g. antibodies and cytokines), have participated in another clinical trial within 6 weeks prior to enrollment, have received systemic hormones (excepting inhaled hormones) within 4 weeks prior to enrollment, or have psychiatric disorders or a history of substance abuse will also be excluded from participation. Any other condition that investigator judges may make patients unsuitable for the trial may also be used as grounds for exclusion.

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CGTLive® reached out to investigators on the trial for commentary on any unique aspects of the trial or recent progress made. The investigators have not yet responded to the request for comment.

Although, CGTLive recently interviewed Renier Brentjens, MD, PhD, the deputy director of the Roswell Park Comprehensive Cancer Center in Buffalo New York. Brentjens was not asked about the Shanxi Bethune Hospital trial, but spoke about the state of CAR-T therapy in hematologic malignancies, and in the broader field of oncology, in a general sense.

“If you look right now at the commercially available CARs—the design of the chimeric receptor—those designs were published back, I think, in 2002 and 2004,” Brentjens told CGTLive. “Since that time, you could stack up all the Science, Nature, and Cell papers, and it'll be about waist high of all these new designs and synNotch receptors and all these other designs and I think one of the frustrating things for me was that—we were as guilty of this as the next person—we kept publishing more ways of curing mice, and it looked better, the doses were lower, and all of this—and of all that technology that was described, much of it remarkably elegant, very little of it has seeped into the realm of translational research, into clinical trials, and for better outcomes. That was actually a significant source of frustration for me, because we were doing all of this, and none of it was actually doing what it was intended to do, which was to translate. Translating cell therapy, unlike drugs that can be manufactured en mass, translating cell therapies is an expensive endeavor.”

REFERENCE
1. Clinical Study of CAR-T Technology for the Treatment of Relapsed Refractory Malignant Haematological Tumours. Clinicaltrials.gov. Website. February 2, 2024. Accessed March 18, 2025. https://clinicaltrials.gov/study/NCT06238336?term=NCT06238336&rank=1