Using donor-derived CAR T cells to treat pediatric B-cell leukemia

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

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 it's running

• 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

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• CD19 and CD22 in vivo CAR-T therapy for relapsed/refractory B-ALL

  This study tests a one-of-a-kind in vivo CAR-T treatment that targets CD19 first and then CD22 in adults with relapsed or refractory B-ALL to see if it is safe and possibly effective.

  Recruiting Phase 1 Chinese PLA General Hospital · Beijing, Beijing Municipality · NCT07927816

• Umbilical Cord Blood CAR-T Cells Targeting CD19 and CD22 for relapsed/refractory B-ALL

  This phase 1 study tests whether dual-target cord blood-derived CAR-T cells against CD19 and CD22 are safe and tolerable in adults with relapsed or refractory B-cell ALL.

  Recruiting Phase 1 Ruijin Hospital · Shanghai, Shanghai Municipality · NCT07838714

• In Vivo CD19/CD20 CAR T-Cell Therapy for Relapsed or Refractory B-Cell Lymphoma

  This early-phase trial tests a one-time in vivo CAR T-cell therapy (SL1617) for people with relapsed or refractory B-cell lymphoma to see if it is safe and tolerable.

  Recruiting Phase 1 Chinese PLA General Hospital · Beijing · NCT07775508

• Dual-target CD22/CD19 CAR-T consolidation after first remission in high-risk B-ALL

  This test will try a dual-target CD22/CD19 CAR-T cell treatment as consolidation for patients with high-risk B-cell acute lymphoblastic leukemia who are in their first remission.

  Recruiting Phase 1/2 Chinese PLA General Hospital · Beijing, Beijing Municipality · NCT07575971

• CD22/CD19 CAR-T consolidation for adults with standard-risk B-ALL

  This study will try dual-target CD22/CD19 CAR-T cell therapy as a consolidation treatment for adults with standard-risk B-cell acute lymphoblastic leukemia who are in first remission.

  Recruiting Phase 1/2 Chinese PLA General Hospital · Beijing, Beijing Municipality · NCT07575919

• Fludarabine dosing for children and young adults with B-cell acute lymphoblastic leukemia

  This trial will test whether pharmacokinetic (PK)-targeted fludarabine dosing before tisagenlecleucel CAR T-cell therapy helps children and young adults with relapsed or refractory B‑cell ALL more than standard fludarabine dosing.

  Recruiting at 7 sites Phase 3 Memorial Sloan Kettering Cancer Center · New York, New York and 7 other locations · NCT07223021

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.