Mitoxantrone Hydrochloride Liposome Injection-containing Bridging Regimen and CD19-targeting CAR-T Therapies

NCT06220097 | Active Not Recruiting Phase 2

• 1 other identifier: bridging regimen of CD19CAR-T
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this open, single-arm practical, phase II, clinical study is to evaluate the efficacy and safety of the mitoxantrone hydrochloride liposome injection-containing regimens in bridging therapies of CD19 CAR-T cells. The main question it aims to answer is: • the efficacy of the mitoxantrone hydrochloride liposome injection-containing combination regimens in bridging therapies of CD19 CAR-T cells. Participants will receive combination bridging regimens including mitoxantrone hydrochloride liposomal injection and CAR-T cell therapy to see if the combination regimens have a positive effect on the efficacy of bridging therapies.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• The overall response rate (ORR) of patients after bridging therapy

  The overall response rate (ORR) was based on the Lugano 2014 Lymphoma Efficacy Evaluation Criteria (Cheson 2014) and the 2021 version of the ALL Efficacy Evaluation Index

  After bridging therapy and before CD19 CAR-T infusion

Secondary Outcomes (3)

• Complete response rate (CR) of patients after bridging therapy and CD19 CAR-T infusion

  within 2 years after infusion

• In vivo expansion and survival of CD19 CAR-T cells

  within 2 years after infusion

• Incidence of Treatment-related Adverse Events

  before bridging therapy and within 2 years after infusion

Study Arms (1)

Effective of MHL injection-containing bridging regimens with CD19 CAR-T

EXPERIMENTAL

After enrollment, all subjects will receive a combination regimen of mitoxantrone hydrochloride liposomal injection within 28 days to 7 days before CAR-T infusions will be included, including but not limited to the R-MINE regimen (mitoxantrone hydrochloride liposomal injection combined with rituximab, mesna, ifosfamide and etoposide), G-MINE regimen (mitoxantrone hydrochloride liposomal injection combined with obinutuzumab, mesna, ifosfamide and etoposide), MAE scheme (mitoxantrone hydrochloride liposomal injection combined with cytarabine, etoposide), etc.

Drug: Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells

Interventions

Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells DRUG

Bridging therapies from enrollment before CD19 CAR-T infusion. A treatment regimen containing mitoxantrone hydrochloride liposome injection, including but not limited to the following recommended regimens: R-MINE regimen (rituximab + ifosfamide + mitoxantrone hydrochloride liposome + etoposide) G-MINE regimen (obinutuzumab + ifosfamide + mitoxantrone hydrochloride liposome + etoposide) MAE regimen (mitoxantrone liposome hydrochloride + cytarabine + etoposide) . The recommended dose of mitoxantrone liposome hydrochloride is not limited. For patients who achieve SD or better after one cycle of bridging treatment, it is up to the investigator to decide whether to receive CAR-T therapy. Fludarabine-based lymphodepletion chemotherapy was followed by CD19 CAR-T cells (relma-cel, axi-cel or humanized CAR19). Relma-cel and axi-cel will be infused according to the instructions. CART19 infusion is conducted at a dose of 1x10\^6/kg on day 0 and day 1 respectively.

Effective of MHL injection-containing bridging regimens with CD19 CAR-T

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged ≥ 18 years and \<75 years.
• Eastern Cooperative Oncology Group score≤ 2.
• 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).
• Flow cytometry (FCM) or immunohistochemistry showed positive CD19 expression in tumor cells;
• Organ function needs to meet the following conditions:
• \) 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.

You may not qualify if:

• 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).
• Hypersensitivity to any of the study drugs or their components.
• 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.
• Investigators judge patients with central nervous system involvement who may be at high risk of receiving bridging therapy and CD19 CAR-T cell treatment.
• Participants with other active malignancies within five years.
• Patients with relapse after allogeneic hematopoietic stem cell transplantation who have had grade 3\~4 acute graft-versus-host response (GVHD).
• Patients who are pregnant or breast-feeding.
• Active autoimmune disease requiring systemic immunosuppressive therapy.
• Other conditions considered to increase the risk to the subject or interfere with the results of the trial by the researcher.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• CSPC Pharmaceutical Group Limited: collaborator

Study Sites (1)

Union Hospital, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

Location

MeSH Terms

Conditions

Burkitt Lymphoma

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: : Proferssor, Cheif Doctor

Study Record Dates

• First Submitted: January 11, 2024
• First Posted: January 23, 2024
• Study Start: February 1, 2022
• Primary Completion: August 1, 2024
• Study Completion: December 30, 2025
• Last Updated: July 17, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)