Using donor-derived CAR T cells to treat pediatric B-cell leukemia
Phase I Clinical Trial on the Use of Fresh, Allogeneic, Second-generation CD19-CAR T Cells for Treatment of Children With Relapsed/Refractory B-cell Acute Lymphoblastic Leukemia
This study is testing a new type of CAR T cell treatment made from donor cells to see if it can help children and young adults with hard-to-treat B-cell leukemia.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 24 (estimated) |
| Ages | 1 Year to 35 Years |
| Sex | All |
| Sponsor | Bambino Gesù Hospital and Research Institute Academic / other |
| Drugs / interventions | Alemtuzumab, chemotherapy, radiation, prednisone, Chimeric Antigen Receptor, CAR T |
| Locations | 1 site (Rome, Italy) |
| Trial ID | NCT06080191 on ClinicalTrials.gov |
What this trial studies
This phase 1, open-label study aims to evaluate the safety and efficacy of allogeneic CD19-directed Chimeric Antigen Receptor T (CAR T) cells in pediatric and young adult patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia (B-ALL). The study will involve a dose-escalation approach to identify the recommended dose of these fresh, donor-derived CAR T cells. Participants will include those who have experienced relapse after previous treatments or those with refractory disease who have a fully matched donor available. The study is designed to provide preliminary evidence of the treatment's effectiveness in this challenging patient population.
Who should consider this trial
Good fit: Ideal candidates are pediatric and young adult patients with relapsed or refractory B-cell Acute Lymphoblastic Leukemia who have a fully matched donor available.
Not a fit: Patients with B-ALL who do not have a suitable donor or who have not failed multiple lines of therapy may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new therapeutic option for children and young adults with difficult-to-treat B-cell leukemia.
How similar studies have performed: Other studies using CAR T cell therapies have shown promising results in treating B-cell malignancies, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
Patient Inclusion Criteria:
1. Patients with a diagnosis of CD19 expressing B ALL relapse, and one of the following:
1. Relapse after alloHSCT OR
2. Relapsed/refractory disease, with failure of frontline therapy and at least 2 rescue strategies, including CD19/CD22-directed monoclonal antibody and availability of a fully matched related donor.
2. CD19+ count ≥ 50 cells/mcl and/or Minimal Residual Disease (MRD) ≥ 10\^-4.
3. Voluntary informed consent. For subjects \< 18-years 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.
4. Clinical performance status: patients \> 16 years of age: Karnofsky greater than or equal to 60%; patients ≤ 16 years of age: Lansky score than or equal to 60%.
5. 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 4 months after receiving the lymphodepletion regimen.
6. Females of child-bearing potential must have a negative pregnancy test because of the potentially dangerous effects on the fetus.
Patients Exclusion Criteria:
1. Pregnant or lactating women.
2. Severe, uncontrolled active intercurrent infections.
3. HIV, or active HCV and/or HBV infection.
4. Life-expectancy \< 6 weeks or rapidly progressive disease that in the evaluation of the investigator would compromise ability to complete study therapy.
5. Hepatic function: inadequate liver function defined as total bilirubin \> 4x upper limit of normal (ULN) or transaminase (ALT and AST) \> 6x ULN.
6. Renal function: serum creatinine \>3x ULN for age.
7. Blood oxygen saturation \< 90%.
8. Cardiac function: left ventricular ejection fraction lower than 45% by ECHO.
9. 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.
10. Presence of active, grade 2-4 acute or chronic Graf versus Host Disease (GvHD) requiring steroid therapy or other immune-suppressive treatment.
11. Relapse occurring before 60 days after alloHSCT.
12. Concurrent or recent prior therapies, before infusion:
i. systemic steroids (at a dose of ≥ 2 mg/kg prednisone) in the 2 weeks before infusion of CD19-CAR\_Lenti\_ALLO cells . Recent or recurrent use of inhaled/topical/non-absorbable steroids is not exclusionary.
ii. systemic chemotherapy in the 2 weeks preceding infusion of CD19-CAR\_Lenti\_ALLO cells .
iii. anti-thymocyte globulin (ATG) or Alemtuzumab (Campath®)in the 8 weeks preceding infusion of CD19-CAR\_Lenti\_ALLO cells .
iv. immuno-suppressive agentis in the 2 weeks preceding infusion of CD19-CAR\_Lenti\_ALLO cells
v. radiation therapy must have been completed at least 2 weeks before infusion of CD19-CAR\_Lenti\_ALLO cells .
vi. other anti-neoplastic investigational agents currently administered or within 30 days prior to infusion of CD19-CAR\_Lenti\_ALLO cells (i.e, start of protocol therapy).
vii. Exceptions:
1. there is no time restrictions in regards to intrathecal chemotherapy, but there must be a complete recovery from any acute toxic effects from such treatment.
2. subjects receiving steroid therapy at physiologic replacement doses only are allowed provided that there has been no increase for at least 2 weeks to starting apheresis.
Donor Eligibility Criteria
Conventional criteria for the eligibility of allogeneic donors will be adopted for the evaluation of cell donors, before apheresis, as required by law.
Where this trial is running
Rome, Italy
- Ospedale Pediatrico Bambino Gesù — Rome, Italy, Italy (Recruiting)
Study contacts
- Principal investigator: Franco Locatelli, MD, PhD — Director Department of Hematology/Oncology and Cell and Gene Therapy
- Study coordinator: Franco Locatelli, MD, PhD
- Email: franco.locatelli@opbg.net
- Phone: +39066859
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.