- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04787263
CD19-CAR_Lenti T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and DLBCL or PML
Phase I/II Study of Anti-CD19 Chimeric Antigen Receptor-Expressing T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ Acute Lymphoblastic Leukemia and Diffuse Large B Cell Lymphoma (DLBCL) or Primary Mediastinal B Cell Lymphoma (PML)
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Franco Locatelli, MD, PhD
- Phone Number: 2678 0039 066859
- Email: franco.locatelli@opbg.net
Study Contact Backup
- Name: Francesca del Bufalo, MD
- Phone Number: 2739 0039 066859
- Email: francesca.delbufalo@opbg.net
Study Locations
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-
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Roma, Italy, 00165
- Recruiting
- IRCCS Ospedale Pediatrico Bambino Gesu
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Contact:
- Franco Locatelli, MD, PhD
- Phone Number: 2678 0039 066859
- Email: franco.locatelli@opbg.net
-
Contact:
- Francesca del Bufalo, MD
- Phone Number: 2739 0039 066859
- Email: francesca.delbufalo@opbg.net
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Principal Investigator:
- Franco Locatelli, MD, PhD
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Principal Investigator:
- Francesca del Bufalo, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Diagnosis of CD19 expressing B-ALL or DLBCL or PML and one of the following:
- Patients in 1st relapse, with High-Risk (HR) features including: MLL- rearrangements, E2A/TCF3-PBX1, TCF3-HLF [t(17;19)], hypodiploidy (i.e., <44 chromosomes), TP53 alterations, early (i.e., <30 months from diagnosis)/very early (i.e., <18 months from diagnosis) isolated or combined bone marrow relapse
- MRD > 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL
- Patients with DLBCL or PML in 1st or subsequent relapse, after at least one standard frontline chemotherapy
- Age: 1 year - 25 years for Bcp-ALL and 1-35 years for B-NHL.
- Voluntary informed consent is given. For subjects < 18 year-old their legal guardian must give informed consent. Pediatric subjects will be included in age-appropriate discussion and verbal assent will be obtained for those greater than or equal to 12 years of age, when appropriate.
- Clinical performance status: Patients > 16 years of age: Karnofsky greater than or equal to 60%; Patients < 16 years of age: Lansky scale greater than or equal to 60%.
- Patients of child-bearing or child-fathering potential must be willing to practice birth control from the time of enrollment on this study and for four months after receiving the preparative regimen.
- Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
Exclusion Criteria:
- Pregnant or lactating women
- Severe, uncontrolled active infections
- HIV, or active HCV and/or HBV infection (detection of viral RNA/DNA in blood)
- Life-expectancy < 6 weeks
- Hepatic function: Inadequate liver function defined as total bilirubin > 4x upper limit of normal (ULN) or transaminase (ALT and AST) > 6 x ULN
- Renal function: serum creatinine > 3x ULN for age.
- Blood oxygen saturation < 90%.
- Cardiac function: Left ventricular ejection fraction lower than 45% by ECHO.
- Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations that would limit compliance with study requirements or in the opinion of the PI would pose an unacceptable risk to the subject.
- BM blasts > 50% pre-infusion.
- Hyperleukocytosis (greater than or equal to 20,000 blasts/microliter) or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy
- Presence of active, grade 2-4 acute or moderate-severe chronic GvHD
- Recurrent or refractory ALL with testicular involvement
Concurrent or recent prior therapies, before infusion:
- Systemic steroids (at a dose > 2 mg/kg prednisone) in the 2 weeks before infusion. Recent or current use of inhaled/topical/non-absorbable steroids is not exclusionary.
- Systemic chemotherapy in the week preceding infusion.
- Anti-thymocyte globulin (ATG) in the 4 weeks preceding infusion.
- Immunosuppressive agents in the 1 week preceding infusion.
- Radiation therapy must have been completed at least 3 weeks prior to enrollment.
- Other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion (i.e. start of protocol therapy);
- Exceptions:
i. There is no time restriction with respect to prior intrathecal chemotherapy, provided that there is complete recovery from any acute toxic effects of such; ii. Patients who relapse while receiving standard ALL maintenance chemotherapy will not be required to have a waiting period before entry onto this study provided that they meet all other eligibility criteria; iii. Subjects receiving steroid therapy at physiologic replacement doses only are allowed provided that there has been no increase in dose for at least 2 weeks prior to starting apheresis;
- Patient-derived CD19-CAR_Lenti production failure: vitality of the fresh product <80%, CD3+ cells <80%, CD3+ CAR+ cells <10%, non-sterility in IPC at day 5, endotoxin contamination (> 5 EU/ml) in IPC at day 5, mycoplasma contamination in IPC at day 5, failure of the visual inspection.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: CD19-CAR_Lenti
Following lymphodepletion with chemotherapy (fludarabine + cyclophosphamide), patients will be treated with 1.0 to 3.0 x 10^6/kg CD19-Chimeric Antigen Receptor (CAR)_Lenti positive cells as a single dose.
The product will be infused fresh, at the end of manufacturing.
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Fresh peripheral blood mononuclear cells are manufactured to obtain CD19-CAR_Lenti T cell, second generation CAR T cells incorporating the 4-1BB costimulatory domain.
The fresh product is infused following lymphodepletion chemotherapy at a dose of 1.0-3.0x10^6
CAR+ cells/kg.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I - Identification of dose limiting toxicities (DLTs) and recommended dose (RD)
Time Frame: 4 weeks after CAR T cell infusion
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Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 5.0
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4 weeks after CAR T cell infusion
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Phase I - Identification of recommended dose (RD)
Time Frame: 4 weeks after CAR T cell infusion of the last patient in the last dose level
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The recommended dose of CD19-CAR_Lenti will be defined as the maximum tolerated dose (MTD) or the highest dose studied, if an MTD is not reached.
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4 weeks after CAR T cell infusion of the last patient in the last dose level
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Phase II - Efficacy
Time Frame: Up to 6 months after CAR T cell infusion
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Bone marrow morphological and minimal residual disease complete remission rate at day 28 after infusion for BCP-ALL; Overall Response Rate (CR, CRi, PR and SD) at day 28, day 90 and day 180 after CAR T cells infusion
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Up to 6 months after CAR T cell infusion
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival (OS)
Time Frame: Up to 2 years
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Up to 2 years
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Relapse Rate (RR)
Time Frame: Up to 2 years
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Up to 2 years
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Disease-Free Survival (DFS)
Time Frame: Up to 2 years
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Up to 2 years
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In vivo persistence/expansion of infused CAR T cell
Time Frame: Up to 2 years
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Detection of infused CAR T cell in the peripheral and bone marrow blood
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Up to 2 years
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Cytokine profiling
Time Frame: Up to 10 days after CAR T cell infusion
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Define serum cytokine profile (Th1/Th2) after T cell infusion and correlation with cytokine release syndrome (CRS)
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Up to 10 days after CAR T cell infusion
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Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- CD19-CAR_Lenti
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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