Actively Recruiting

Phase 1
Age: 1Year - 35Years
All Genders
ID06080191

Phase I Clinical Trial of Fresh, Allogeneic, Second-generation CD19-CAR T Cells for Children and Young Adults With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia

Led by Bambino Gesù Hospital and Research Institute · Updated on 2025-12-02

24

Participants Needed

1

Research Sites

778 weeks

Total Duration

On this page

AI-Summary

What this Trial Is About

Researchers are evaluating fresh, donor-derived CD19-directed second-generation Chimeric Antigen Receptor T (CAR T) cells in pediatric and young adult patients with relapsed or refractory B-cell precursor Acute Lymphoblastic Leukemia (BCP-ALL). This phase 1, open-label, single-center study aims to assess the safety, determine the recommended dose, and gather preliminary evidence of efficacy in patients who have relapsed after or before allogeneic hematopoietic stem cell transplantation (alloHSCT) with a fully matched donor available. Participants receive a single intravenous infusion of CD19-CAR_Lenti_ALLO cells on Day 0 following a lymphodepletion regimen with fludarabine and cyclophosphamide given on days -5, -4, and -3. Patients are assigned to two cohorts based on donor HLA matching: cohort A with fully matched family or unrelated donors and cohort B with haploidentical donors. Dose levels vary by cohort, and an additional lower dose level may be explored if dose-limiting toxicities occur. During the study, participants will be closely monitored for safety, including dose-limiting toxicities over 28 days, and for graft-versus-host disease occurrence and severity over one year. Researchers will also evaluate treatment responses such as complete response and minimal residual disease negativity. Follow-up includes survival assessment over one year. The study involves detailed clinical evaluations and laboratory tests to ensure thorough monitoring of each participant.

CONDITIONS

Brief Title

Allogeneic Second-generation CD19-CAR T Cells for Pediatric Relapsed/Refractory B-ALL

Who Can Participate

Age: 1Year - 35Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Patients diagnosed with CD19-expressing B-cell Acute Lymphoblastic Leukemia relapse
  • Relapse after allogeneic hematopoietic stem cell transplantation (alloHSCT) or relapsed/refractory disease with failure of frontline therapy and at least two rescue treatments including CD19/CD22 monoclonal antibody
  • Availability of a fully matched related donor
  • CD19+ cell count of at least 50 cells/mcL or minimal residual disease (MRD) of at least 10^-4
  • Voluntary informed consent; for those under 18, legal guardian consent and verbal assent for those 12 or older when appropriate
  • Clinical performance status: Karnofsky score ≥ 60% if older than 16 years; Lansky score ≥ 60% if 16 years or younger
  • Willingness to use birth control from enrollment through 4 months after lymphodepletion
  • Negative pregnancy test for females of child-bearing potential
Not Eligible

You will not qualify if you...

  • Pregnant or lactating women
  • Severe uncontrolled infections
  • HIV or active hepatitis C or B infection
  • Life expectancy less than 6 weeks or rapidly progressing disease compromising study completion
  • Liver function with total bilirubin > 4 times upper limit of normal or transaminases > 6 times upper limit
  • Kidney function with serum creatinine > 3 times upper limit for age
  • Blood oxygen saturation below 90%
  • Left ventricular ejection fraction below 45% by echocardiogram
  • Congestive heart failure, cardiac arrhythmia, psychiatric illness, or social situations limiting study compliance or posing risk
  • Active grade 2-4 acute or chronic graft-versus-host disease requiring steroids or immunosuppressive therapy
  • Relapse occurring less than 60 days after alloHSCT
  • Recent systemic steroids (≥ 2 mg/kg prednisone) or chemotherapy within 2 weeks before infusion
  • Recent anti-thymocyte globulin or Alemtuzumab within 8 weeks before infusion
  • Recent immunosuppressive agents within 2 weeks before infusion
  • Radiation therapy completed less than 2 weeks before infusion
  • Other investigational anti-cancer agents within 30 days before infusion
  • Exceptions include intrathecal chemotherapy with recovery and stable physiologic steroid replacement doses
  • Donors must meet conventional eligibility for allogeneic donation as required by law

AI-Screening

AI-Powered Screening

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Run-in Period

Duration - 3 days

Participants receive lymphodepletion chemotherapy with fludarabine and cyclophosphamide before CAR T cell infusion.

Daily visits for 3 days

Treatment

Duration - Single day

Participants receive a single intravenous infusion of donor-derived CD19-CAR T cells on Day 0.

1 infusion visit (in-person)

Follow-up

Duration - Up to 1 year

Participants are monitored for safety, efficacy, and occurrence of graft-versus-host disease and other outcomes after treatment.

Regular follow-up visits for up to 1 year

Trial Site Locations

Total: 1 location

1

Ospedale Pediatrico Bambino Gesù

Rome, Italy, Italy, 00165

Actively Recruiting

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Research Team

F

Franco Locatelli, MD, PhD

F

Francesca del Bufalo, MD, PhD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

NONE

Allocation

NA

Model

SINGLE_GROUP

Primary Purpose

TREATMENT

Number of Arms

1

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