Combination of Mitoxantrone Liposome Injection and CD19 CAR-T Therapy for B-cell Malignancies

Study on the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Injection-containing Bridging Regimen in CD19-targeting CAR-T Therapies

This study is testing a new combination treatment of a special injection and CAR-T therapy to see if it helps people with tough-to-treat B-cell cancers while they wait for their CAR-T cells to be ready.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 28 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Wuhan Union Hospital, China (Academic / other)
• Drugs / interventions: CAR-T, chemotherapy, doxorubicin, Chimeric antigen receptor
• Locations: 1 site (Wuhan, Hubei)
• Trial ID: NCT06220097 on ClinicalTrials.gov

What this trial studies

This phase II clinical trial evaluates the safety and efficacy of a combination regimen that includes mitoxantrone hydrochloride liposome injection and CD19-targeting CAR-T cell therapy for patients with refractory or relapsed B-cell malignancies. The study aims to determine if this bridging therapy can effectively control disease progression while patients await CAR-T cell preparation. Participants will receive the combination treatment to assess its impact on treatment outcomes. The trial is designed to address the urgent need for effective bridging therapies in this patient population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 to 75 with refractory or relapsed B-cell malignancies who express CD19 in their tumor cells.

Not a fit: Patients with non-B-cell malignancies or those who do not meet the eligibility criteria will not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly improve patient outcomes by providing effective disease control during the waiting period for CAR-T therapy.

How similar studies have performed: Other studies have shown promise with CAR-T therapies, but the specific combination of mitoxantrone liposome injection and CAR-T is a novel approach.

Eligibility criteria

Inclusion Criteria:

1. Aged ≥ 18 years and \<75 years.
2. Eastern Cooperative Oncology Group score≤ 2.
3. Clinically diagnosed refractory or relapsed B-cell malignancies. Relapse refers to "relapse after a complete response (CR) from initial chemotherapy"; refractory refers to "diagnosis can be made if any of the following are met:(1) tumor shrinkage of \<50% or disease progression (PD) after standard chemotherapy; (2) CR is achieved by standard chemotherapy but relapses within six months, (3) 2 or more recurrences after CR, (4) recurrence after hematopoietic stem cell transplantation"; B-cell malignancies include the following 3 categories: (1) B-cell acute lymphoblastic leukemia (B-ALL); (2) indolent B-cell lymphoma (CLL, FL, MZL); (3) aggressive B-cell lymphoma (DLBCL, BL, MCL).
4. Flow cytometry (FCM) or immunohistochemistry showed positive CD19 expression in tumor cells;
5. Organ function needs to meet the following conditions:

1) EF \>50%, and there is no obvious abnormality on ECG; 2) SpO2≥90%； 3) Cr≤2.5 ULN; 4) ALT and AST≤5 ULN, TBil≤3 ULN; 6. Negativity of blood pregnancy test for women, and participants use effective methods of contraception until the last follow-up. 7. The patient or his or her legal guardian voluntarily participates in and signs an informed consent form.

Exclusion Criteria:

1. Prior treatment with doxorubicin or other anthracyclines with a total cumulative dose of doxorubicin \>360 mg/m2 (other anthracyclines convert 1 mg of doxorubicin to 2 mg epirubicin).
2. Hypersensitivity to any of the study drugs or their components.
3. Concomitant other diseases that are not effectively controlled, including but not limited to persistent or poorly controlled infections, symptomatic congestive heart failure, unstable angina, cardiac arrhythmias, poorly controlled pulmonary diseases, or psychiatric disorders.
4. Investigators judge patients with central nervous system involvement who may be at high risk of receiving bridging therapy and CD19 CAR-T cell treatment.
5. Participants with other active malignancies within five years.
6. Patients with relapse after allogeneic hematopoietic stem cell transplantation who have had grade 3\~4 acute graft-versus-host response (GVHD).
7. Patients who are pregnant or breast-feeding.
8. Active autoimmune disease requiring systemic immunosuppressive therapy.
9. Other conditions considered to increase the risk to the subject or interfere with the results of the trial by the researcher.

Where this trial is running

Wuhan, Hubei

• Union Hospital, Huazhong University of Science and Technology — Wuhan, Hubei, China (Recruiting)

Conditions B-cell Acute Lymphoblastic Leukemia; B-cell Lymphoma Refractory