Phase I Clinical Trial of CART Cell Therapy for Refractory/Relapsed Acute Lymphoblastic Leukemia in Children, Adolescents and Young Adults

NCT06709469 | Recruiting Phase 1 DMC

• 1 other identifier: HULP 6614
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test the feasibility and safety of an academic production of two different anti-CD19 chimeric antigen receptor T cells (CART) products according to the different biomarkers of the disease in children and young adults with relapsed/refractory CD19+ B cell acute lymphoblastic leukemia (r/r B-ALL) or relapsed/refractory T-cell acute lymphoblastic leukemia (r/r T-ALL). The main questions it aims to answer are:

1. 1.The safety and feasibility of autologous CART-19/22 in children, adolescents and young adults with a CD19+/- CD22+ relapse/ refractory disease for a r/r B-ALL.
2. 2.The safety and feasibility of allogeneic CART-NKG2D (chimeric-antigen receptor Natural-killer group 2, member D) in children, adolescents and young adults with r/r T-ALL.

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Outcome Measures

Primary Outcomes (2)

• Incidence and severity of adverse events in patients that received autologous CART-19/22

  An adverse event is any harmful and unintended reaction to an investigational medicinal product, regardless of the dose administered. Adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of CRS and ICANS, which will be graded according to ASBMT Consensus Grading. If CTCAE grading does not exist for an AE, the severity of mild, moderate, severe, life-threatening and fatal, corresponding to Grades 1-5, will be used.

  Through study completion, an average of 5 years

• Incidence and severity of adverse events in patients that received allogenic CART-NKG2D T

  An adverse event is any harmful and unintended reaction to an investigational medicinal product, regardless of the dose administered. Adverse events will be assessed and graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0, with the exception of CRS and ICANS, which will be graded according to ASBMT Consensus Grading. If CTCAE grading does not exist for an AE, the severity of mild, moderate, severe, life-threatening and fatal, corresponding to Grades 1-5, will be used.

  Through study completion, an average of 5 years

Secondary Outcomes (6)

• Expression of CD19/CD22 and NKG2DL on primary B- or T- cell ALL, respectively

  Through study completion, an average of 5 years

• Persistence of CART19/22 and CART-NKG2D cells in patients' samples

  Through study completion, an average of 5 years

• Cytokine profile

  Through study completion, an average of 5 years

• DNA methylation profile of NKG2DL

  Through study completion, an average of 5 years

• Presence of soluble NKG2DL, and ANTI-MICA and ANTI-MICB antibodies

  Through study completion, an average of 5 years

Other Outcomes (2)

• Incidence of serious adverse events

  Through study completion, an average of 5 years

• Performance status

  Through study completion, an average of 5 years

Study Arms (2)

Arm A

EXPERIMENTAL

Children and young adults with CD19+/- CD22+ B-ALL with relapsed or refractory disease not responding to conventional chemotherapy and with no other curative therapy available.

Biological: Autologous CD19/CD22 CAR T cells

Arm B

EXPERIMENTAL

Children and youn adults with T-ALL with relapsed or refractory disease not responding to conventional chemotherapy and with no other curative therapy available.

Biological: Allogeneic CART-NKG2D cells

Interventions

Autologous CD19/CD22 CAR T cells BIOLOGICAL

A total of two doses of autologous CD19/CD22 CAR T cells (first dose of up to 0.75x106/kg fresh cells), and a second infusion of unfrozen cells (same dose) if there has been no ≥ grade 1 cytokine-release syndrome (CRS) in the next 72 h; intravenously.

Arm A

Allogeneic CART-NKG2D cells BIOLOGICAL

A total of up to 3x106/kg allogeneic CART-NKG2D cells divided in three doses of up to 1x106/kg will be infused; intravenously. First infusion of fresh cells, and the 2nd and 3rd infusion of unfrozen cells (same dose) if there has been no ≥ grade 1 CRS (every 48 hours).

Arm B

Eligibility Criteria

• Age: Up to 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead

Study Sites (1)

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

RECRUITING

Related Publications (1)

• Gonzalez-Martinez B, Galan-Gomez V, Navarro-Zapata A, Mirones-Aguilar I, Cobo M, Pernas-Sanchez A, Vallejo S, Sanchez-Zapardiel E, Leon-Triana O, Echecopar C, Martinez-Romera I, Guerra-Garcia P, San Roman-Pacheco S, Escudero A, Izquierdo E, Izquierdo M, Naharro S, Martin-Ayuso A, Bareke H, Paris-Munoz A, Hu P, Schneider D, Orentas RJ, Minguillon J, Perez-Martinez A. Tandem CD19/CD22 CAR T-cells as potential therapy for children and young adults with high-risk r/r B-ALL. EBioMedicine. 2025 Aug;118:105872. doi: 10.1016/j.ebiom.2025.105872. Epub 2025 Aug 5.

  PMID: 40753722 DERIVED

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Condition Hierarchy (Ancestors)

Leukemia, Lymphoid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Central Study Contacts

Antonio Pérez Martínez, MD

CONTACT

917 27 75 76; aperezmartinez@salud.madrid.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Phase I, open label, prospective, single center, two-armed, non-randomized trial

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: November 29, 2024
• Study Start: July 8, 2025
• Primary Completion (Estimated): June 1, 2030
• Study Completion (Estimated): December 1, 2030
• Last Updated: September 22, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1)