Phase I CAR T-cell therapy for relapsed or refractory acute lymphoblastic leukemia in children, adolescents, and young adults

A Phase I Clinical Trial of CART Cell Therapy for Refractory/ Relapsed Acute Lymphoblastic Leukemia With Unmet Needs in Children, Adolescents and Young Adults: Feasibility and Safety Study (REALL_CART).

This phase I study will test two CAR T-cell approaches to see if they are safe and feasible for children and young adults with relapsed or refractory B-ALL or T-ALL.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: N/A to 30 Years
• Sex: All
• Sponsor: Instituto de Investigación Hospital Universitario La Paz (other)
• Drugs / interventions: CART, CAR-T, chemotherapy, prednisone, chimeric antigen receptor, CAR T
• Locations: 1 site (Madrid, Madrid)
• Trial ID: NCT06709469 on ClinicalTrials.gov

What this trial studies

This Phase I trial uses an academic manufacturing approach to deliver two different CAR T-cell products matched to disease biomarkers in pediatric and young adult patients with relapsed or refractory acute lymphoblastic leukemia. Patients with CD19+/- CD22+ B-ALL receive autologous CD19/CD22 CAR T cells, while patients with T-ALL receive allogeneic CAR T cells using an NKG2D receptor. The primary goals are to determine feasibility and safety, with close monitoring for toxicity, CAR T-cell persistence, and early signs of remission. Patients who enter remission may proceed to allogeneic hematopoietic stem cell transplant per investigator judgment.

Who should consider this trial

Good fit: Children, adolescents, and young adults with relapsed or refractory CD19+/- CD22+ B-ALL or relapsed/refractory T-ALL who have failed conventional chemotherapy and meet performance, laboratory, and donor (for T-ALL) eligibility criteria are the intended participants.

Not a fit: Patients with very limited life expectancy (<12 weeks), poor organ function or performance status, uncontrolled infection, or without a suitable donor for the T-ALL arm are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, these approaches could provide new targeted options that induce remission in patients with relapsed or refractory B-ALL or T-ALL who currently have few effective therapies.

How similar studies have performed: Anti-CD19 CAR T cells have produced high response rates in CD19+ B-ALL but relapses are common, and CAR approaches for T-ALL are much less established, while dual CD19/CD22 and NKG2D strategies have shown promising preclinical and early compassionate-use signals.

Eligibility criteria

Inclusion Criteria:

* ARM A: CD19+/- CD22+ B-ALL with relapsed or refractory disease not responding to conventional chemotherapy and with no other curative therapy available. Treatment with previous CART CD19 therapy is permitted, but is not mandatory, OR:
* ARM B: T-ALL with relapsed or refractory disease not responding to conventional chemotherapy and with no other curative therapy available.
* Patients diagnosed with ALL must be suitable for allogeneic HSCT and willing to proceed to transplant if the CART treatment induces complete remission and the investigator believes it is the best option.
* For ARM B there must be a suitable haploidentical donor (following local standard operating procedures).
* Lansky (age \<16 years) or Karnofsky (age ≥16 years) score of 50 or greater.
* Life expectancy greater than 12 weeks.
* Absolute neutrophil count (ANC) ≥ 500/μL unless, in the opinion of the investigator, cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy.
* Platelet count ≥ 50,000/μL unless, in the opinion of the investigator, cytopenia is due to underlying leukemia and is potentially reversible with leukemia therapy.
* Absolute lymphocyte count ≥ 100/μL.
* Adequate renal, hepatic, pulmonary, and cardiac function.
* Adequate venous access and absence of contraindications for lymphoapheresis
* Patients with a seizure disorder may be enrolled if well controlled with anticonvulsants.
* Patients or patients' legal representative, parent(s), or guardian able to provide written informed consent.

Exclusion Criteria:

* Enrolled in another clinical trial in the previous 4 weeks.
* Active infection requiring systemic medical therapy including clinically significant viral infection or uncontrolled viral reactivation of EBV, CMV, adenovirus, BK-virus, HHV-6 or Aspergillus.
* Any of the following cardiac criteria: cardiac echocardiography with LVSF\<30% or LVEF\<40%; or clinically significant pericardial effusion.
* Presence of CNS-3 disease or uncontrolled seizure disorder.
* Active immunosuppressive therapy with the exception of prednisone 10 mg/day (or equivalent), within 7 days prior to enrolment.
* GFR \<30 ml/min or bilirubin \>3 times the upper limit of normality (unless due to Gilbert's syndrome).
* Any other condition that, in the opinion of the PI, may interfere with the efficacy and/or safety evaluation of the trial.
* Pregnant or lactating women.
* Sexually active patients must be willing to utilize one of the more effective birth control methods for at least 12 months after the infusion and until CAR-T cells are no longer present on two consecutive tests. Male partner should use a condom. Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant.
* Sexually active males should use a condom during intercourse for at least 12 months after the infusion and until CAR-T cells are no longer present on two consecutive tests.

Where this trial is running

Madrid, Madrid

• Hospital Universitario La Paz — Madrid, Madrid, Spain (RECRUITING)

Study contacts

• Study coordinator: Antonio Pérez Martínez, MD

Conditions: Precursor Cell Lymphoblastic Leukemia-Lymphoma