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

NCT06752785 | Recruiting Phase 1 DMC

• 1 other identifier: 2024423A01
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Lymphoblastic Leukemia

Keywords

B-ALL, CAR-T

Outcome Measures

Primary Outcomes (1)

• Validity exploration

  According to the efficacy evaluation criteria for ALL in the "NCCN Clinical Practice Guidelines for Acute Lymphoblastic Leukemia (2024.V5)", the complete remission(CR) rate will be evaluated at 1 year after CAR-T treatment.CR is generally measured in percentage(%).

  One year after CAR-T treatment

Study Arms (1)

MRD-Positive B-lineage Acute Lymphoblastic Leukemia

EXPERIMENTAL

Children of MRD-Positive B-lineage Acute Lymphoblastic Leukemia; CD19/CD22 CAR-T

Drug: CAR-T Therapy

Interventions

CAR-T Therapy DRUG

CD19/CD22 CAR-T cell therapy

MRD-Positive B-lineage Acute Lymphoblastic Leukemia

Eligibility Criteria

• Age: 1 Year - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Parents or legal guardians fully understand, are informed of this study and sign the informed consent form (ICF); are willing to follow and can complete all test procedures.
• Chinese children aged 1-18 years old at the time of screening, regardless of gender, with a body weight ≥ 10 kg.
• Bone marrow examination confirms that MRD is still positive on the 46th day after induction remission.
• Tumor cells in the bone marrow (BM) or peripheral blood (PB) express CD19/CD22 within 3 months before screening.
• Good organ function, which needs to meet the following criteria: (1)ALT ≤ 5 times the upper limit of normal value (ULN); (2)total bilirubin ≤ 2 times ULN (Gilbert's syndrome ≤ 3 times ULN); (3)without \> grade 1 dyspnea when not inhaling oxygen, and oxygen saturation \> 95%; (4)left ventricular ejection fraction (LVEF) ≥ 50%; (5)serum creatinine ≤ 1.5 times ULN.
• Karnofsky score (≥ 16 years old) ≥ 70 or Lansky (\< 16 years old) score ≥ 50.
• Expected survival period of at least 12 weeks.
• Have sufficient venous access (for apheresis or venous blood sampling), and have no other contraindications for blood cell separation.

You may not qualify if:

• Have genetic diseases, except Down syndrome.
• Have a history of other malignancies or have other malignancies simultaneously.
• 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 the upper limit of normal value; (3)human immunodeficiency virus antibody (HIV-Ab) positive; (4)Treponema pallidum antibody (TP-Ab) positive; (5)EBV DNA higher than the upper limit of normal value; (6)cytomegalovirus DNA higher than the upper limit of normal value.
• Have or are suspected to have uncontrolled or require intravenous drug treatment for fungal, bacterial, viral or other infections.
• Long-acting G-CSF is prohibited within 21 days before screening, and short-acting G-CSF is prohibited within 7 days before screening.
• Have active central nervous system leukemia.
• Are allergic to albumin and aminoglycoside antibiotics.
• Have undergone organ transplantation (except hematopoietic stem cell transplantation).
• Have participated in other interventional clinical studies within 3 months before screening (received active test drug treatment), or intend to participate in another clinical trial or receive anti-tumor treatment other than that specified in the protocol during the entire study period.
• Cannot tolerate chemotherapy and cytokine storm due to impaired function of important organs.
• Other situations that the investigator deems not suitable for participating in this clinical trial.

Sponsors & Collaborators

• Guangzhou Women and Children's Medical Center: lead

Study Sites (1)

Guangzhou Medical University Affiliated Women and Children's Medical Center

Guangzhou, Guangdong, 510623, China

RECRUITING

Related Publications (6)

• Cordoba S, Onuoha S, Thomas S, Pignataro DS, Hough R, Ghorashian S, Vora A, Bonney D, Veys P, Rao K, Lucchini G, Chiesa R, Chu J, Clark L, Fung MM, Smith K, Peticone C, Al-Hajj M, Baldan V, Ferrari M, Srivastava S, Jha R, Arce Vargas F, Duffy K, Day W, Virgo P, Wheeler L, Hancock J, Farzaneh F, Domning S, Zhang Y, Khokhar NZ, Peddareddigari VGR, Wynn R, Pule M, Amrolia PJ. CAR T cells with dual targeting of CD19 and CD22 in pediatric and young adult patients with relapsed or refractory B cell acute lymphoblastic leukemia: a phase 1 trial. Nat Med. 2021 Oct;27(10):1797-1805. doi: 10.1038/s41591-021-01497-1. Epub 2021 Oct 12.

  PMID: 34642489 BACKGROUND

• Wang T, Tang Y, Cai J, Wan X, Hu S, Lu X, Xie Z, Qiao X, Jiang H, Shao J, Yang F, Ren H, Cao Q, Qian J, Zhang J, An K, Wang J, Luo C, Liang H, Miao Y, Ma Y, Wang X, Ding L, Song L, He H, Shi W, Xiao P, Yang X, Yang J, Li W, Zhu Y, Wang N, Gu L, Chen Q, Tang J, Yang JJ, Cheng C, Leung W, Chen J, Lu J, Li B, Pui CH. Coadministration of CD19- and CD22-Directed Chimeric Antigen Receptor T-Cell Therapy in Childhood B-Cell Acute Lymphoblastic Leukemia: A Single-Arm, Multicenter, Phase II Trial. J Clin Oncol. 2023 Mar 20;41(9):1670-1683. doi: 10.1200/JCO.22.01214. Epub 2022 Nov 8.

  PMID: 36346962 BACKGROUND

• Pan J, Tang K, Luo Y, Seery S, Tan Y, Deng B, Liu F, Xu X, Ling Z, Song W, Xu J, Duan J, Wang Z, Li C, Wang K, Zhang Y, Yu X, Zheng Q, Zhao L, Zhang J, Chang AH, Feng X. Sequential CD19 and CD22 chimeric antigen receptor T-cell therapy for childhood refractory or relapsed B-cell acute lymphocytic leukaemia: a single-arm, phase 2 study. Lancet Oncol. 2023 Nov;24(11):1229-1241. doi: 10.1016/S1470-2045(23)00436-9. Epub 2023 Oct 17.

  PMID: 37863088 BACKGROUND

• Buechner J, Caruana I, Kunkele A, Rives S, Vettenranta K, Bader P, Peters C, Baruchel A, Calkoen FG. Chimeric Antigen Receptor T-Cell Therapy in Paediatric B-Cell Precursor Acute Lymphoblastic Leukaemia: Curative Treatment Option or Bridge to Transplant? Front Pediatr. 2022 Jan 25;9:784024. doi: 10.3389/fped.2021.784024. eCollection 2021.

  PMID: 35145941 BACKGROUND

• Pui CH, Yang JJ, Hunger SP, Pieters R, Schrappe M, Biondi A, Vora A, Baruchel A, Silverman LB, Schmiegelow K, Escherich G, Horibe K, Benoit YC, Izraeli S, Yeoh AE, Liang DC, Downing JR, Evans WE, Relling MV, Mullighan CG. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration. J Clin Oncol. 2015 Sep 20;33(27):2938-48. doi: 10.1200/JCO.2014.59.1636. Epub 2015 Aug 24.

  PMID: 26304874 BACKGROUND

• Pui CH, Yang JJ, Bhakta N, Rodriguez-Galindo C. Global efforts toward the cure of childhood acute lymphoblastic leukaemia. Lancet Child Adolesc Health. 2018 Jun;2(6):440-454. doi: 10.1016/S2352-4642(18)30066-X. Epub 2018 Mar 30.

  PMID: 30169285 BACKGROUND

MeSH Terms

Conditions

Precursor Cell Lymphoblastic Leukemia-Lymphoma

Interventions

Immunotherapy, Adoptive

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

Intervention Hierarchy (Ancestors)

Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Biological Therapy; Therapeutics; Immunologic Techniques; Investigative Techniques

Study Officials

• Hua Jiang, phd

  Guangzhou Medical University Affiliated Women and Children's Medical Center

  STUDY DIRECTOR

Central Study Contacts

Hua Jiang, phd

CONTACT

86-020-38076051; jiang_hua18@sina.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 12, 2024
• First Posted: December 31, 2024
• Study Start: October 1, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): June 30, 2028
• Last Updated: December 31, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)