Anti‑CD19 CAR‑T plus a BTK inhibitor for newly diagnosed high‑risk CLL/SLL

The Efficacy of AntiCD19 CAR-T Combined With BTKi in the Treatment of Newly Diagnosed High-risk CLL Patients, and to Explore Its Efficacy and Safety of Limited-term Treatment in These Patients

We will try combining anti‑CD19 CAR‑T cells with a BTK inhibitor as first‑line treatment for people newly diagnosed with high‑risk CLL or SLL.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 50 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: The Affiliated Hospital of Xuzhou Medical University (Academic / other)
• Drugs / interventions: chemotherapy, prednisone, CAR-T
• Locations: 1 site (Xuzhou, Jiangsu)
• Trial ID: NCT07120633 on ClinicalTrials.gov

What this trial studies

Eligible newly diagnosed high‑risk CLL/SLL patients will be screened, give informed consent, and have blood taken for HIV testing and for autologous T cell collection and manufacturing feasibility. If the patient's cells are suitable, anti‑CD19 CAR‑T cells will be produced and the patient will receive CAR‑T infusion together with a BTK inhibitor. Participants will be monitored for MRD in peripheral blood and bone marrow, CAR‑T cell expansion, and treatment toxicity every three months for one year. After that one‑year on‑site follow‑up, subjects will enter a two‑year telephone and questionnaire phase to track long‑term outcomes and quality of life.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed, treatment‑naive, CD19‑positive high‑risk CLL or SLL who meet iwCLL 2018 treatment indications and can undergo CAR‑T manufacturing and follow‑up are ideal candidates.

Not a fit: Patients who have had prior systemic chemotherapy or radiotherapy, whose disease is CD19‑negative, who have uncontrolled active infections or serious comorbidities, or whose cells cannot be manufactured into CAR‑T are unlikely to benefit.

Why it matters

Potential benefit: If successful, the combination could raise the rate of undetectable minimal residual disease, improve long‑term outcomes, and reduce the need for long‑term medication in high‑risk CLL/SLL patients.

How similar studies have performed: Anti‑CD19 CAR‑T has shown activity in relapsed/refractory CLL and BTK inhibitors are effective in high‑risk disease, but combining them as a first‑line approach for newly diagnosed high‑risk CLL/SLL is largely novel with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. The patient voluntarily participates and signs the informed consent form;
2. Age ≥18 years old;
3. Confirmed as CLL/SLL according to WHO standards, and confirmed positive expression of CD19 through flow cytometry or immunohistochemical detection;
4. Subjects:

   4.1 First-time patients who have not received systemic radiotherapy or chemotherapy in the past. (Except for the following situations: Short-term systemic corticosteroids for disease control, improvement of performance status or treatment of non-cancer indications (use for ≤14 days, prednisone \<100 mg/d or dexamethasone ≤20 mg/d). Steroids must be discontinued before the study of treatment. Inhaled steroids, topical steroids and alternative corticosteroids are permitted for the treatment of asthma.

   4.2 Meet the treatment indications of iwCLL 2018, including: Progressive bone marrow failure caused by bone marrow infiltration due to CLL (hemoglobin \<10 g/L and platelet count \<100×10⁹/L); 4.3 Patients with high-risk genetic molecular factors (del(17p), TP53 gene deletion/mutation (vaf\>10%), U-IGHV, complex karyotype); 4.4 Have measurable or evaluable lesions (positive peripheral blood flow results or lesions ≥1cm evaluated based on PET-CT/CT/MRI).

   4.5 No contraindications for treatment with Bruton's tyrosine kinase (BTK) inhibitors or BCL2 inhibitors.
5. Good functions of major tissues and organs:

   5.1 Liver function: ALT/AST\<3 times the upper limit of the normal value and total bilirubin ≤34.2 μmol/L; 5.2 Renal function: Creatinine \< 220 μmol/L; 5.3 Pulmonary function: Indoor oxygen saturation ≥95%; 5.4 Cardiac function: Left ventricular ejection fraction ≥40%.
6. The peripheral superficial veins have smooth blood circulation and can accept intravenous infusion.
7. ECOG score ≤2;
8. The expected survival period is more than three months.

Exclusion Criteria:

1. CLL patients who have undergone Richter transformation;
2. Patients known to have active malignant tumors involving the central nervous system. For patients who have previously suffered from central nervous system diseases and have received effective treatment, if they have completed treatment for at least 3 months before enrollment, have no evidence of symptomatic diseases, and the imaging examination shows abnormal stability, they will be considered for enrollment.
3. There is a history of primary malignant tumor, and it has not been relieved for at least two years. The following situations are not subject to the two-year limit: non-melanoma skin cancer, completely resected stage 1 solid tumors with low recurrence risk, radical treatment of local prostate cancer, biopsion-revealed cervical cancer in situ or smear-revealed squamous intraepithelial lesions, and completely resected breast cancer in situ.
4. Active hepatitis B, hepatitis C, syphilis or human immunodeficiency virus infection;
5. There was an uncontrollable systemic fungal, bacterial or viral infection within 4 weeks before enrollment;
6. Have a history of any of the following cardiovascular diseases within the past 6 months: grade III or IV heart failure as defined by the New York Heart Association, angioplasty or stent implantation, myocardial infarction, unstable angina pectoris, clinically obvious arrhythmia, or other clinically significant heart diseases;
7. Women who are pregnant (with a positive urine/blood pregnancy test) or breastfeeding;
8. Patients who are allergic to large molecule biological drugs such as antibodies or cytokines;
9. Had systemic hormones or immunosuppressive drugs been used within 4 weeks before enrollment (except for patients with inhaled hormones);
10. Suffer from mental illness;
11. The researcher determined that the patient had other conditions that made him unsuitable for inclusion in the group.

Where this trial is running

Xuzhou, Jiangsu

• The Affiliated Hospital of Xuzhou Medical University — Xuzhou, Jiangsu, China (Recruiting)

Study contacts

• Study coordinator: Wei Sang, Ph.D.

Conditions CLL; CAR-T Cell Therapy; SLL; CAR-T