CD19/CD22 CAR-T Cell Therapy in MRD-Positive B-lineage Acute Lymphoblastic Leukemia in Children.

Last updated: December 29, 2024
Sponsor: Guangzhou Women and Children's Medical Center
Overall Status: Active - Recruiting

Phase

1

Condition

Leukemia

Lymphoproliferative Disorders

Platelet Disorders

Treatment

CAR-T Therapy

Clinical Study ID

NCT06752785
2024423A01
  • Ages 1-18
  • All Genders

Study Summary

In this study, CD19/CD22 dual-target CAR-T therapy will be carried out among children patients who are still positive after induction remission, and subsequent chemotherapy will continue after CAR-T cells exert their functions. This study intends to use retroviral vector-based tandem CAR-T cells targeting CD19/CD22 to treat MRD-positive ALL. The CAR-T cells were provided by Shenzhen Cell Valley. The results of the research team from Stanford University School of Medicine in the United States have already demonstrated the feasibility and safety of producing bispecific CD19/CD22.BB.z-CAR T cells in a closed system as well as the high clinical activity shown in the treatment of CAR19-resistant B-ALL (B-lineage acute lymphoblastic leukemia) and LBCL (Large B-cell lymphoma). The investigators look forward to expanding the application of CAR-T cells in MRD positive B-ALL through this clinical study on safety and efficacy and greatly improving the prognosis of children patients with this type of B-ALL.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  1. Parents or legal guardians fully understand, are informed of this study and sign theinformed consent form (ICF); are willing to follow and can complete all testprocedures.

  2. Chinese children aged 1-18 years old at the time of screening, regardless of gender,with a body weight ≥ 10 kg.

  3. Bone marrow examination confirms that MRD is still positive on the 46th day afterinduction remission.

  4. Tumor cells in the bone marrow (BM) or peripheral blood (PB) express CD19/CD22within 3 months before screening.

  5. Good organ function, which needs to meet the following criteria: (1)ALT ≤ 5 timesthe upper limit of normal value (ULN); (2)total bilirubin ≤ 2 times ULN (Gilbert'ssyndrome ≤ 3 times ULN); (3)without > grade 1 dyspnea when not inhaling oxygen, andoxygen saturation > 95%; (4)left ventricular ejection fraction (LVEF) ≥ 50%; (5)serum creatinine ≤ 1.5 times ULN.

  6. Karnofsky score (≥ 16 years old) ≥ 70 or Lansky (< 16 years old) score ≥ 50.

  7. Expected survival period of at least 12 weeks.

  8. Have sufficient venous access (for apheresis or venous blood sampling), and have noother contraindications for blood cell separation.

Exclusion

Exclusion Criteria:

  1. Have genetic diseases, except Down syndrome.

  2. Have a history of other malignancies or have other malignancies simultaneously.

  3. Meet any of the following conditions: (1)hepatitis B surface antigen (HBsAg)positive or HBV DNA quantification higher than the upper limit of normal value; (2)hepatitis C antibody (HCV Ab) positive and HCV RNA quantification higher than theupper limit of normal value; (3)human immunodeficiency virus antibody (HIV-Ab)positive; (4)Treponema pallidum antibody (TP-Ab) positive; (5)EBV DNA higher thanthe upper limit of normal value; (6)cytomegalovirus DNA higher than the upper limitof normal value.

  4. Have or are suspected to have uncontrolled or require intravenous drug treatment forfungal, bacterial, viral or other infections.

  5. Long-acting G-CSF is prohibited within 21 days before screening, and short-actingG-CSF is prohibited within 7 days before screening.

  6. Have active central nervous system leukemia.

  7. Are allergic to albumin and aminoglycoside antibiotics.

  8. Have undergone organ transplantation (except hematopoietic stem celltransplantation).

  9. Have participated in other interventional clinical studies within 3 months beforescreening (received active test drug treatment), or intend to participate in anotherclinical trial or receive anti-tumor treatment other than that specified in theprotocol during the entire study period.

  10. Cannot tolerate chemotherapy and cytokine storm due to impaired function ofimportant organs.

  11. Other situations that the investigator deems not suitable for participating in thisclinical trial.

Study Design

Total Participants: 10
Treatment Group(s): 1
Primary Treatment: CAR-T Therapy
Phase: 1
Study Start date:
October 01, 2024
Estimated Completion Date:
June 30, 2028

Study Description

This clinical trial is a single-center, open-label, single-arm clinical trial to evaluate the safety and efficacy of CAR-T cell treatment for MRD-positive B-ALL. The specific trial process is divided as follows:

  1. Screen the enrolled population to determine the indications and exclusion criteria for cell treatment. In brief, intermediate-risk patients with positive MRD on day 46 of induction through flow cytometry according to CCCG-ALL regimen.

  2. Sign the informed consent form.

  3. CAR-T cell preparation: collect autologous lymphocytes and produce CAR-T cells targeting the CD19/CD22 target.

  4. Lymphocyte depletion pretreatment: according to the patient's condition, select the FC regimen (fludarabine 30 mg/m²/day for 4 days; cyclophosphamide 500 mg/m²/day for 2 days) before autologous transplantation.

  5. Cell intravenous infusion: dose: 3 × 10⁶/kg (allowable fluctuation range: 2 × 10⁶/kg

    • 4 × 10⁶/kg). Obeserve adverse reactions including CRS and ICANS.

  6. Evaluate the efficacy after the first cell infusion by MRD test .

  7. Continue chemotherapy after one month of CART according CCCG-ALL regimen from the second high-dose MTX of consolidation stage.

  8. Follow-up after the completion of the clinical study: within the first month after cell infusion, the subject needs to complete the relevant examinations required for follow-up on the 7th, 14th, 21st, and 30th days. Depending on the patient's condition, the number of detections may also be increased; from the 2nd to 6th months after infusion, follow-up once a month; from 6 months to 2 years after infusion, follow-up once every 3 months. From 2 to 5 years after infusion, follow-up once a year. After that, enter long-term follow-up.

Connect with a study center

  • Guangzhou Medical University Affiliated Women and Children's Medical Center

    Guangzhou, Guangdong 510623
    China

    Active - Recruiting

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