2023-506348-17-00
尚未招募
2 期
A single-arm, multi-center, open-label Phase II study to determine the safety and efficacy of MB-CART2019.1 in pediatric subjects with relapsed/refractory (r/r) mature B-cell neoplasms who have relapsed after one or more prior therapies, including subjects with primary refractory disease
概览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 12
- 试验地点
- 6
- 主要终点
- • Type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI). Primary efficacy estimand:
概览
简要总结
The primary objective is to assess the safety, toxicity and efficacy of MB-CART2019.1 therapy, as measured by best overall response rate (BORR), after infusion in subjects with relapsed/refractory (r/r) mature B cell neoplasms.
入排标准
- 年龄范围
- 0 years 至 17 years（0-17 Years）
- 接受健康志愿者
- 是
入选标准
- •1.Subjects must meet all the following inclusion criteria to be eligible for inclusion in this study: Is able to provide age-appropriate assent/consent (as applicable, according to local legislation) and/or have a guardian able to provide consent signed and dated by the parent(s) or by subject’s legal guardian before conduct of any study-specific procedures.
- •Tissue samples archival or fresh (preferred) from recent relapse or initial diagnosis (in case of primary refractory disease) must be made available for the central pathology review to confirm diagnosis (≤2 years, preferably not older than 2 months since collection).
- •Has Karnofsky (aged ≥16 years) or Lansky (aged <16 years) performance status ≥
- •Has adequate bone marrow function as defined by the following laboratory values (as assessed by local laboratory for eligibility): o Absolute neutrophil count (ANC) >1000/µL. o Platelets ≥50000/µL. o Hemoglobin ≥8.0 g/dL. o Absolute lymphocyte count ≥100/µL.
- •Is willing to undergo collection of non-mobilized leukapheresis.
- •In the opinion of the investigator, the subject must be able to comply with all study related procedures, medication use, and assessments.
- •Has adequate organ function as follows: o Renal function: estimated glomerular filtration rate (eGFR) >29 mL/min by Schwartz formula (Schwartz et al 1976). o Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤5 × upper limit of normal (ULN) for age. o Bilirubin <1.5 x ULN (for Gilbert’s Syndrome, subject’s total bilirubin <4 mg/dL). o Adequate pulmonary function as follows: - Resting oxygen saturation of ≥91% on room air. - No or mild dyspnea (Grade ≤1)."
- •Female subjects of childbearing potential must be willing to undergo pregnancy tests before MB-CART2019.1 infusion.
- •If subjects are sexually active, they must be willing to use highly effective methods of contraception. o Female subjects must agree to use two methods of contraception; - one of the following methods (Pearl index <1%): Hormonal contraceptives associated with inhibition of ovulation (oral, intravaginal, injected, implanted, transdermal), intrauterine devices (IUDs) or systems (e.g., hormonal and non-hormonal IUD), or vasectomized sexual partner AND one barrier method. - Highly effective methods of contraception must be followed from inclusion until 12 months after MB-CART2019.1 infusion. o Male subjects must agree to use a condom during intercourse from inclusion through at least 12 months after MB-CART2019.1 infusion to prevent them from fathering a child AND to prevent delivery of MB-CART2019.1 via seminal fluid to their partner. Do not use a female condom when using a male condom, since tearing can occur. In addition, male subjects must not donate sperm for the time period specified above. o Females must agree not to breast feed or donate eggs/ova during the study and until at least 12 months after MB-CART2019.1 infusion.
- •Has histologically confirmed mature CD19+ and/or CD20+ B-cell neoplasm according to the WHO 2022 classification of hematolymphoid tumors such as:o Burkitt lymphoma/Burkitt leukemia o Diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS) o Primary mediastinal (thymic) large B-cell lymphoma o Burkitt-like lymphoma with 11q aberration o Aggressive mature B-cell lymphoma o Other rare aggressive B-cell non-Hodgkin lymphoma (NHL) after sponsor approval."
排除标准
- •Is receiving active treatment for malignant disease (including participation in any additional parallel investigational drug or device studies), except for pre-enrollment therapy, including radiotherapy. Lesions that are irradiated during pre-enrollment therapy may not be considered measurable lesions. For subjects with lymphoma to be eligible, there must be at least one measurable lesion after pre-enrollment therapy.
- •Presence of active or prior hepatitis B or C as indicated by serology. Treated infection with hepatitis B or C virus unless confirmed to be polymerase chain reaction (PCR) negative.
- •Has infection with Treponema pallidum.
- •Has active infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2).
- •Has infection with human T-lymphotropic virus 1/2 (HTLV 1/2).
- •14.Has active severe systemic fungal, viral, or bacterial infection, requiring systemic antiviral, antifungal, or antimicrobial therapy.
- •Has clinically significant seizures according to the opinion of by the investigator.
- •Has history of cerebral vascular accident within 12 months prior to leukapheresis.
- •Has impaired cardiac function: Fractional shortening <28% or left ventricular ejection fraction <50% by echocardiography or multigated acquisition, if allowed as per local law.
- •Has concomitant genetic syndromes associated with bone marrow (BM) failure status, such as Fanconi anemia, Kostmann syndrome, Shwachman syndrome, or any other known BM failure syndrome.
结局指标
主要结局
• Type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI). Primary efficacy estimand:
• Type, frequency, and severity of adverse events (AEs), serious adverse events (SAEs), and adverse events of special interest (AESI). Primary efficacy estimand:
BORR, defined as the proportion of subjects with at least one partial response (PR) or complete response (CR) based on independent review committee (IRC) assessment from MB-CART2019.1 infusion until progressive disease (PD), start of new anti lymphoma therapy, lost to follow-up or death due to any cause, whichever occurs first.
BORR, defined as the proportion of subjects with at least one partial response (PR) or complete response (CR) based on independent review committee (IRC) assessment from MB-CART2019.1 infusion until progressive disease (PD), start of new anti lymphoma therapy, lost to follow-up or death due to any cause, whichever occurs first.
次要结局
- Key secondary efficacy endpoints • BORR until Week 24, defined as the proportion of subjects with at least one PR or CR after the MB-CART2019.1 infusion, based on IRC assessment until Week 24.
- • CRR, defined as the proportion of subjects with at least one CR assessment, based on IRC assessment. "
- • DOR, defined as the time between the date of first objective response (CR/PR) until the date of PD, based on IRC assessment, or lost to follow-up, or death due to any cause, whichever occurs first. "
- • DOCR, defined as the time between the date of first CR until the date of PD, based on IRC assessment, or lost to follow-up, or death due to any cause, whichever occurs first. "
- • TTR, defined as the time between the date of MB-CART2019.1 infusion and the date of a first objective response (CR/PR), based on IRC assessment. "
- • TTCR, defined as the time between the date of MB-CART2019.1 infusion and the date of a first objective CR, based on IRC assessment. "
- • ORR, defined as the proportion of subjects with a PR or CR, based on IRC assessment, at the following visits: Day 28, Week 8, Week 12, Week 24, Week 52, and Week 78. "
- • EFS, defined as the time between the date of the MB-CART2019.1 infusion and the date of an event (PD, start of a new anti-lymphoma therapy after MB-CART2019.1 infusion excluding hematopoietic stem cell transplantation [HSCT], relapse, or death due to any cause), based on IRC assessment. "
- • PFS, defined as the time between the date of MB-CART2019.1 infusion and the date of PD based on IRC assessment, or lost to follow-up, or death due to any cause, whichever occurs first. "
- • OS, defined as the time between the date of MB-CART2019.1 infusion and the date of death due to any cause, irrespective of new anti-lymphoma therapy. "
- • OS rates at Week 52 and at Week 78. "
- • BORR, based on investigator assessment. "
- • BORR until Week 24, based on investigator assessment. "
- • CRR, based on investigator assessment. "
- • DOR, based on investigator assessment. "
- • DOCR, based on investigator assessment.
- • TTR, based on investigator assessment. "
- • TTCR, based on investigator assessment. "
- • ORR, based on investigator assessment, at the following visits: Day 28, Week 8, Week 12, Week 24, Week 52, and Week 78. "
- • EFS, based on investigator assessment. "
- • PFS, based on investigator assessment.
- • Occurrence and persistence of B-cell aplasia. "
- • The proportion of subjects who proceed to HSCT after MB-CART2019.1 infusion until end of study (EOS). "
- • Types and levels of cytokines (including soluble interleukin-2 receptor [sIL-2R], IL-6, IL-10, IL-15, interferon gamma [IFN-γ], and tumor necrosis factor alpha [TNF-α])
- • Persistence and phenotype of MB-CART2019.1, based on flow cytometry analyses and persistence based on quantitative polymerase chain reaction (qPCR). "
- • Anti-MB-CART2019.1 antibody via anti-drug antibody assay "
- • Change from baseline in HRQoL, using the EuroQol-5 Dimensions-Youth (EQ-5D-Y) questionnaire"
- • Hospital days within 6 months after MB-CART2019.1 infusion. "
- • Intensive care unit (ICU) admission days within 6 months after MB-CART2019.1 infusion. "
- • Use of tocilizumab and/or high-dose steroids and/or anti-interleukin medication. "
- • Need for transfusions, prophylactic antimicrobial therapy, and gamma globulin substitution within 12 months after MB-CART2019.1 infusion.
- • Change in clinical laboratory assessments, physical and neurological examinations, and electrocardiogram (ECG) parameters within 6 months after MB-CART2019.1 infusion. "
- • Monitoring of RCL by qPCR"
- • CD19/CD20 antigen expression in tumor biopsies in case of relapse after MB-CART2019.1 infusion
研究者
Clinical Trial Desk
Scientific
Miltenyi Biomedicine GmbH
研究点 (6)
Loading locations...
相似试验
招募中
不适用
Study of CART Cell (MB-CART19.1) in Patients With Relapsed or Refractory CD19 Positive NHLNCT07271121King Hussein Cancer Center26
尚未招募
不适用
A Study of DB-1324 in Advanced/Metastatic Gastrointestinal TumorsNCT07263594DualityBio Inc.127
招募中
1 期
A Trial of LBL-024 Monotherapy or Combination Drug in Patients With Triple Negative Breast CancerNCT07281976Nanjing Leads Biolabs Co.,Ltd220
招募中
3 期
A Study to Investigate the Efficacy and Safety of Fitusiran Prophylaxis in Male Participants Aged 1 to Less Than 12 Years With Hemophilia A or BNCT07285460Sanofi85
尚未招募
不适用
NANT 2021-02: Randomized MIBG With Vorinostat/Dinutuximab/Vorinostat + DinutuximabNCT07261241New Approaches to Neuroblastoma Therapy Consortium118