B-cell Acute Lymphoblastic LeukemiaPhase 2NCT06220097
Mitoxantrone Hydrochloride Liposome Injection-containing Bridging Regimen and CD19-targeting CAR-T Therapies
A Phase 2 study testing Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells in people with B-cell Acute Lymphoblastic Leukemia and B-cell Lymphoma Refractory, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- B-cell Acute Lymphoblastic Leukemia, B-cell Lymphoma Refractory
- What is being tested?
- Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteChina
- Study dates
- 1 Feb 2022to 30 Dec 2025
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
- 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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
China1 site
Union Hospital, Huazhong University of Science and Technology
Wuhan, Hubei, 430022
About this study
Official title: Study on the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Injection-containing Bridging Regimen in CD19-targeting CAR-T Therapies
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.
Read the detailed description
Chimeric antigen receptor T-cell (CAR-T) therapy has been approved for a variety of relapsed/refractory hematologic malignancies and has significantly improved patient outcomes. The preparation of CAR-T cells, including a variety of relevant individual factors, usually takes at least 3-4 weeks, or more, so patients may require bridging therapy (BT) to control disease progression and prevent the rapid exacerbation of systemic cancer. Clinical trial data have shown that about 7% of patients do not survive while waiting for CAR-T cell preparation to be completed, so individual bridging therapy can be given after apheresis and 4-6 weeks before CAR-T infusion to achieve effective CAR-T cell therapy.
Mitoxantrone, a traditional anthracycline quinone, is an antibiotic antineoplastic drug. It exerts antitumor effects by interfering with DNA, RNA, and inhibition of topoisomerase II, and is a cell cycle non-specific drug[]. Liposomes are excellent carriers of anti-tumor drugs, which can reduce the distribution of drugs in normal tissues and increase the accumulation of drugs in tumor tissues, thereby reducing toxicity and improving treatment efficacy. To reduce the toxicity of mitoxantrone and improve its efficacy, CSPC Pharmaceutical Group has developed the liposomal formulation of mitoxantrone, which is based on liposomal R\&D technology. A new technical upgrade has been carried out on the mitoxantrone liposome, making it the only liposome with a higher dosage than the ordinary preparation, and it is a new anthracycline liposome that has been comprehensively upgraded. In the pivotal phase II study of liposomal mitoxantrone, monotherapy with PTCL was associated with an ORR of 41.7%, a CR rate of 23.1%, a median PFS of 8.5 months, a median OS not reached, and a high incidence of adverse events such as neutropenia and pigmentation, with a good cardiac safety profile and no progression of cardiotoxicity. Single-agent 16mg/m2 and 20mg/m2 doses were also explored in DLBCL, and 35 patients with relapsed and refractory DLBCL were enrolled, with an overall objective response rate of 38.5% in the 26 full analysis sets, which had certain activity in DLBCL.
- Being tested
- Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells
- Medical subject headings
- Burkitt Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T CellsDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
CR will be assessed from CAR-T cell infusion to death or last follow-up (censored)
Measured: within 2 years after infusion
In vivo expansion and survival of CD19 CAR-T cells
The quantity of CD19 CAR copies in bone marrow, peripheral blood and cerebrospinal fluid will be determined by using a quantitative polymerase chain reaction.
Measured: within 2 years after infusion
Incidence of Treatment-related Adverse Events
Therapy-related adverse events (AE), including severe adverse events (SAE) and laboratory outliers with clinical significance, will be recorded and assessed according to the National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0).
Measured: before bridging therapy and within 2 years after infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Jan 2024
- Study start1 Feb 2022
- Primary completion1 Aug 2024
- Study completion30 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for B-cell Acute Lymphoblastic LeukemiaStudies of the same condition, open and under way.
- More trials run by Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 28 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- CSPC Pharmaceutical Group Limited
- Responsible party
- Principal investigator, MEI HENG, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06220097
- Sponsor's protocol ID
- bridging regimen of CD19CAR-T
- Status last verified
- Jan 2025
- First submitted
- 11 Jan 2024
- Last updated
- 17 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study on the Safety and Efficacy of Mitoxantrone Hydrochloride Liposome Injection-containing Bridging Regimen in CD19-targeting CAR-T Therapies
- ClinicalTrials.gov ID
- NCT06220097
- Acronym / sponsor ID
- bridging regimen of CD19CAR-T
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 28 participants (estimated)
- Lead sponsor
- Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyUniversity, hospital or other
- Collaborators
- CSPC Pharmaceutical Group Limited
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Aug 2024 (actual)
- Study completion
- 30 Dec 2025 (estimated)
- First posted
- 23 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Chimeric antigen receptor T-cell (CAR-T) therapy has been approved for a variety of relapsed/refractory hematologic malignancies and has significantly improved patient outcomes. The preparation of CAR-T cells, including a variety of relevant individual factors, usually takes at least 3-4 weeks, or more, so patients may require bridging therapy (BT) to control disease progression and prevent the rapid exacerbation of systemic cancer. Clinical trial data have shown that about 7% of patients do not survive while waiting for CAR-T cell preparation to be completed, so individual bridging therapy can be given after apheresis and 4-6 weeks before CAR-T infusion to achieve effective CAR-T cell therapy.
Mitoxantrone, a traditional anthracycline quinone, is an antibiotic antineoplastic drug. It exerts antitumor effects by interfering with DNA, RNA, and inhibition of topoisomerase II, and is a cell cycle non-specific drug[]. Liposomes are excellent carriers of anti-tumor drugs, which can reduce the distribution of drugs in normal tissues and increase the accumulation of drugs in tumor tissues, thereby reducing toxicity and improving treatment efficacy. To reduce the toxicity of mitoxantrone and improve its efficacy, CSPC Pharmaceutical Group has developed the liposomal formulation of mitoxantrone, which is based on liposomal R\&D technology. A new technical upgrade has been carried out on the mitoxantrone liposome, making it the only liposome with a higher dosage than the ordinary preparation, and it is a new anthracycline liposome that has been comprehensively upgraded. In the pivotal phase II study of liposomal mitoxantrone, monotherapy with PTCL was associated with an ORR of 41.7%, a CR rate of 23.1%, a median PFS of 8.5 months, a median OS not reached, and a high incidence of adverse events such as neutropenia and pigmentation, with a good cardiac safety profile and no progression of cardiotoxicity. Single-agent 16mg/m2 and 20mg/m2 doses were also explored in DLBCL, and 35 patients with relapsed and refractory DLBCL were enrolled, with an overall objective response rate of 38.5% in the 26 full analysis sets, which had certain activity in DLBCL.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Effective of MHL injection-containing bridging regimens with CD19 CAR-T | Experimental | Drug: Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T CellsAfter 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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:
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T CellsBridging 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. | Drug | Effective of MHL injection-containing bridging regimens with CD19 CAR-T |
Primary outcome
The overall response rate (ORR) of patients after bridging therapy
Time frame: After bridging therapy and before CD19 CAR-T infusion
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
3 secondary outcomes
Complete response rate (CR) of patients after bridging therapy and CD19 CAR-T infusion
Time frame: within 2 years after infusion
In vivo expansion and survival of CD19 CAR-T cells
Time frame: within 2 years after infusion
Incidence of Treatment-related Adverse Events
Time frame: before bridging therapy and within 2 years after infusion
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Jul 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells in people with B-cell Acute Lymphoblastic Leukemia and B-cell Lymphoma Refractory, run by Union Hospital, Tongji Medical College, Huazhong University of Science and Technology at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 17 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The overall response rate (ORR) of patients after bridging therapy (time frame: After bridging therapy and before CD19 CAR-T infusion). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Jul 2025.