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Trial Title:
Mitoxantrone Hydrochloride Liposome Injection-containing Bridging Regimen and CD19-targeting CAR-T Therapies
NCT ID:
NCT06220097
Condition:
B-cell Acute Lymphoblastic Leukemia
B-cell Lymphoma Refractory
Conditions: Official terms:
Precursor Cell Lymphoblastic Leukemia-Lymphoma
Fludarabine
Mitoxantrone
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Mitoxantrone hydrochloride liposome Injection-based bridging therapy+ Fludarabine-based chemotherapy +CD19 CAR-T Cells
Description:
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.
Arm group label:
Effective of MHL injection-containing bridging regimens with CD19 CAR-T
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.
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.
Criteria for 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Union Hospital, Huazhong University of Science and Technology
Address:
City:
Wuhan
Zip:
430022
Country:
China
Status:
Recruiting
Contact:
Last name:
Heng Mei, M.D., Ph.D
Phone:
027-8572600
Email:
hmei@hust.edu.cn
Contact backup:
Last name:
Yun Kang
Phone:
17362995329
Email:
cloudykang@hust.edu.cn
Investigator:
Last name:
Heng Mei, M.D., Ph.D
Email:
Principal Investigator
Investigator:
Last name:
Danying Liao, M.D., Ph.D
Email:
Sub-Investigator
Start date:
February 1, 2024
Completion date:
December 30, 2025
Lead sponsor:
Agency:
Wuhan Union Hospital, China
Agency class:
Other
Collaborator:
Agency:
CSPC Pharmaceutical Group Limited
Agency class:
Industry
Source:
Wuhan Union Hospital, China
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06220097
