CD19-CAR_Lenti T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and DLBCL or PML

NCT04787263 | Active Not Recruiting Phase 1

• 1 other identifier: CD19-CAR_Lenti
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims at evaluating the feasibility and safety of the administration of autologous T cells that have been modified through the introduction of a chimeric antigen receptor targeting the B-cell surface antigen CD19, following administration of lymphodepleting chemotherapy regimen, in children and adults with relapsed/refractory B-cell acute lymphoblastic leukemia (B- ALL) or aggressive B-cell Non-Hodgkin lymphoma (B-NHL). The phase II extension is aimed at testing the efficacy of the treatment at the optimal dose defined in the phase I. In addition, the investigators hypothesize that it is feasible to successfully manufacture CAR T cells to meet the established release criteria at a maximum target dose of 3.0 x 10\^6 cells/kilogram recipient total body weight in this patient population using the Miltenyi CliniMACS Prodigy® closed transduction system.

Conditions

Acute Lymphoblastic Leukemia; Diffuse Large B Cell Lymphoma; Primary Mediastinal Lymphoma

Outcome Measures

Primary Outcomes (3)

• Phase I - Identification of dose limiting toxicities (DLTs) and recommended dose (RD)

  Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 5.0

  4 weeks after CAR T cell infusion

• Phase I - Identification of recommended dose (RD)

  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.

  4 weeks after CAR T cell infusion of the last patient in the last dose level

• Phase II - Efficacy

  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

  Up to 6 months after CAR T cell infusion

Secondary Outcomes (5)

• Relapse Rate (RR)

  Up to 2 years

• Overall survival (OS)

  Up to 2 years

• Disease-Free Survival (DFS)

  Up to 2 years

• In vivo persistence/expansion of infused CAR T cell

  Up to 2 years

• Cytokine profiling

  Up to 10 days after CAR T cell infusion

Study Arms (1)

CD19-CAR_Lenti

EXPERIMENTAL

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.

Biological: CD19-CAR_Lenti T cell

Interventions

CD19-CAR_Lenti T cell BIOLOGICAL

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.

CD19-CAR_Lenti

Eligibility Criteria

• Age: 1 Year - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 chemotherapy in the week preceding infusion.

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead

Study Sites (1)

IRCCS Ospedale Pediatrico Bambino Gesù

Roma, 00165, Italy

Location

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma; Lymphoma, Large B-Cell, Diffuse

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Lymphoma

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2021
• First Posted: March 8, 2021
• Study Start: March 4, 2021
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 3, 2038
• Last Updated: December 2, 2025

Record last verified: 2025-11

Locations

IT (1)