Anti-CD19 CAR T Cells in Pediatric Patients Affected by Relapsed/Refractory CD19+ ALL and NHL

NCT03373071 | Completed Phase 1 DMC

• 1 other identifier: CD19-CAR01
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of this phase I study is to evaluate the safety and to establish the recommended dose of CD19-CART01 infused in pediatric patients affected by relapsed/refractory B-ALL or NHL with measurable Bone Marrow (BM) involvement. The phase II extension is aimed at testing the efficacy of the treatment at the optimal dose defined in the phase I.

Conditions

CD19-ALL; CD19-LNH

Keywords

CD19-CAR T cell; CD19-malignancy; CAR T cell; CD19-ALL; CD19-LNH

Outcome Measures

Primary Outcomes (2)

• Phase I - Identification of the dose limiting toxicity (DLT)

  Toxicity will be assessed according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) scale, version 4 and the number of patients experiencing DLT will be evaluated

  4 weeks after CAR T cell infusion

• Phase II - Efficacy

  Complete remission rate minimal residual disease (MRD) negative response

  4 weeks after CAR T cell infusion

Secondary Outcomes (8)

• Overall Response Rate (ORR)

  4 weeks after CAR T cell infusion

• In vivo persistence/expansion of infused CAR T cell

  Up to 5 years

• Function of infused CAR T cell

  Up to 5 years

• Cytokine profiling

  10 days after CAR T cell infusion

• Disease Outcome

  Up to 3 years

Study Arms (1)

CD19-CART01

EXPERIMENTAL

Following the lymphodepleting treatment, with patients will be treated with 0.5 to 3.0 x 10⁶/kg CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose

Biological: CD19-CAR T cell

Interventions

CD19-CAR T cell BIOLOGICAL

Following lymphodepletion with chemotherapy (cyclophosphamide and fludarabine) patients will be treated with 0.5 to 3.0 x 10⁶/kg CD19 Chimeric Antigen Receptor (CAR) positive T cells as a single dose. In case of toxicity, the patient will receive the dimerizing drug activating the suicide safety switch in order to improve the safety of the treatment

CD19-CART01

Eligibility Criteria

• Age: 6 Months - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Male and female subjects with CD19 expressing B-cell acute lymphoblastic leukemia (ALL) or Non-Hodgkin Lymphoma (NHL) with BM involvement and one of the following:
• i. Patients in 2nd or subsequent relapse, after at least one standard frontline chemotherapy and one salvage regimen, with BM involvement ii. Relapse after allogeneic HSCT, if at least 100 days post-transplant, if there is no evidence of active GVHD and if the patient is no longer taking immunosuppressive agents for at least 30 days prior to enrollment iii. MRD \> 0.1% after either reinduction therapy or any course of consolidation for relapsed ALL
• Measurable or evaluable disease at the time of enrollment, which may include any evidence of disease, including MRD detected by flow cytometry, cytogenetics, or polymerase chain reaction (PCR) analysis.
• Age: 6 months - 25 years.
• 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 intercurrent infections
• HIV, or active HCV and/or HBV infection
• 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
• Active CNS disease as documented by the presence of blasts in the CSF or by MRI. This criterion could be revised once that, after the phase I portion of the study, absence of life-threatening (i.e. grade IV) neurological toxicity will be documented.
• Presence of active, grade 2-4 acute or extensive chronic GvHD
• Recurrent or refractory ALL with testicular involvement
• Concurrent or recent prior therapies, before infusion:

Sponsors & Collaborators

• Bambino Gesù Hospital and Research Institute: lead

Study Sites (1)

Ospedale Pediatrico Bambino Gesù

Roma, Italy

Location

Related Publications (1)

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Haematology-Oncology Department Chief

Study Record Dates

• First Submitted: December 6, 2017
• First Posted: December 14, 2017
• Study Start: December 23, 2017
• Primary Completion: May 11, 2021
• Study Completion: January 24, 2025
• Last Updated: February 5, 2025

Record last verified: 2025-02

Locations

IT (1)