MB-CART19.1 in Patients With R/R ALL
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|ClinicalTrials.gov Identifier: NCT03321123|
Recruitment Status : Unknown
Verified October 2017 by Shanghai Children's Medical Center.
Recruitment status was: Not yet recruiting
First Posted : October 25, 2017
Last Update Posted : October 25, 2017
|Condition or disease||Intervention/treatment||Phase|
|Precursor B-Lymphoblastic Lymphoma/Leukaemia Refractory||Drug: MB-CART19.1||Phase 2|
This is an open-label, non-randomized phase II paediatric study. In this study, eligible patients will receive autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1) at a doesage of 2x10e6 ~2x10e7 CAR-transduced T cells/kg.
Upon enrollment, leukapheresis will be performed for MB-CART19.1 generation. Patients with high disease burden at screening (e.g. ALL with M3 marrow and 10.000/L blasts in peripheral blood) may receive bridging chemotherapy after leukapheresis, to avoid critical tumor lysis syndrome and cytokine release syndrome (CRS) by subsequent lymphodepleting chemotherapy and CAR transfer.
All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells.
Patients will receive freshly prepared MB-CART19.1 on day 0, corresponding to day 12 (48 hours) of manufacturing, at a dose of 2x10e6 ~2x10e7/kg MB-CART19.1 T cells as defined in the study design section. The appropriate volume for the target cell dose will be drawn up and given as an IV injection over 30 minutes through a large vein peripherally or centrally.
The primary objectives are:
- To assess the safety and tolerability of MB-CART19.1.
- To evaluate the biological activity of adoptive transfer of autologous MB-CART19.1 in patients with R/R CD19-positive B cell lymphoblastic leukemia.
The primary endpoint is Overall response rate (ORR):ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Adoptive Therapy With MB-CART19.1 in Patients With Relapsed/Refractory CD19-positive B Cell Acute Lymphoblastic Leukemia|
|Estimated Study Start Date :||December 1, 2017|
|Estimated Primary Completion Date :||July 1, 2019|
|Estimated Study Completion Date :||December 31, 2019|
Experimental: CRA treatment
The drug for this trial is autologous T cells transduced with the lentiviral vector pLTG1563 (MB-CART19.1). The dose is 2x10e6 ~2x10e7 MB-CART19.1/kg.
A leukapheresis for the patient will be performed for MB-CART19.1 generation. All patients will receive lymphodepleting chemotherapy with fludarabine 30 mg/m2/d intravenously (iv) on days -5,-4,-3 and -2 cyclophosphamide 500 mg/m2/d iv on day -3,-2 before CAR T cell transfer to enhance the in vivo expansion of CAR T cells.
Miltenyi Biotec has established a semi-automated manufacturing process that can be made available to academic settings for systematic exploration of CAR strategies in advanced clinical studies. Closed-system operation, improved robustness, simplified work flows, and reduced labor intensity, while maintaining strict adherence to regulatory guidelines, allows for decentralized manufacturing. In this study, we will explore autologous 2nd generation CD19 CAR T cell products in patients with relapsed and refractory disease incurable with standard therapies.
Other Name: Miltenyi CD-19 CAT-T cell
- Overall response rate [ Time Frame: 1 Month ]ORR in ALL patients is defined as the rate of complete remission (CR, CRh) on day 28
- Overall incidence and severity of adverse events. [ Time Frame: 1 Months ]Overall incidence and severity of adverse events will measure in this trial. Including: 1,Risks related to targeting of CD19+ normal B-cells; 2,Allergic reactions to CAR T cell infusion; 3, Cytokine release syndrome (CRS); 4, neurological toxicities; 5,Risks related to transfer of donor T cells after previous alloSCT; 6, Risks related to lentiviral gene transfer into human cells.
- Rate of ALL patients achieving MRD negative CR [ Time Frame: 12 Months ]The rate of ALL patients achieving MRD negative CR in D28; 3,6,12months.
- Relapse rate and time to relapse [ Time Frame: 12 Months ]Overall rate of relapse and the time to relapse from CART cell transfused.
- Disease-free and overall survival at 1 year after adoptive immunotherapy with MB-CART19.1 in patients not receiving alloSCT [ Time Frame: 12 Months ]CART treatment is an adoptive immunotherapy, and the CART cells will disaper after infusion. Then the patient relapsed. Allo-SCT can rebuild a new immune system to detec and destory cancer cell.
- Level of circulating CAR T cells [ Time Frame: 12 Months ]CART treatment is an adoptive immunotherapy, and the CART cells will disaper after infusion. The investigator need to detec the circulating CAR-T cell after infusion regularly.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03321123
|Contact: Jing Chen, MD, PhD||86 firstname.lastname@example.org|
|Contact: Benshang Li, MD, PhD||86 email@example.com|
|Principal Investigator:||Jing Chen, MD,PhD||Shanghai Children Medicine Center|