CD19 & CD22 Bispecific CAR T Cells in the Treatment of Relapsed/Refractory B Cell Hematologic Tumors

NCT06735495 | Recruiting Phase 1 DMC

• 1 other identifier: CD19 & CD22 bispecific CAR T
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study is a multi-center, open, prospective single-arm clinical study of patients with relapsed / refractory B cell hematological tumors to evaluate the safety and efficacy of CD19 \& CD22 bispecific CAR-T cells in relapsed / refractory B cell hematological tumors while collecting pharmacokinetics and pharmacodynamics indicators of CAR-T cells.

Conditions

B-Cell Lymphoblastic Leukemia/Lymphoma

Keywords

CAR-T; dual-target; Relapsed / Refractory B Cell Hematological Tumors

Outcome Measures

Primary Outcomes (4)

• Overall response rate (ORR) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors

  Disease overall response rate (ORR) will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

• Complete response rate (CR) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors

  CR will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

• Complete response with incomplete blood recovery rate (CRi) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors

  CRi will be assessed from CAR-T cell infusion to death or last follow-up (censored).

  within 3 years after infusion

• Partial response rate (PR) of administering CD19&CD22 dual-target CAR-T cells In the treatment of relapsed/refractory B-cell hematologic tumors

  PR will be assessed from CAR-T cell infusion to death or last follow-up.

  within 3 years after infusion

Secondary Outcomes (7)

• Duration of Response (DOS) of administering CD19&CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors

  within 3 years after infusion

• Progress-free survival (PFS) of administering CD19&CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors

  within 3 years after infusion

• Overall survival (OS) of administering CD19&CD22 dual-target CAR-T cells in the treatment of relapsed/refractory B-cell hematologic tumors

  within 3 years after infusion

• The Peripheral blood vector copy number of patients of CD19&CD22 dual-target CAR-T cell therapy in relapsed/refractory B-cell hematological malignancies

  within 3 years after infusion

• The Cmax of CAR T cells of CD19&CD22 dual-target CAR-T cell therapy in relapsed/refractory B-cell hematological malignancies

  within 3 years after infusion

Study Arms (1)

Effective of CD19&CD22 bispecific CAR-T cells

EXPERIMENTAL

The infusion dose range of cells in this trial is recommended: 1 to 2 10\^6 And CAR-T cells / kg.

Drug: CD19&CD22 bispecific CAR-T cells

Interventions

CD19&CD22 bispecific CAR-T cells DRUG

Each patient will receive CD19\&CD22 bispecific CAR-T cells by intravenous infusion on day 0

Effective of CD19&CD22 bispecific CAR-T cells

Eligibility Criteria

• Age: 3 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• CD 19 + / CD 22 + B cell hematological tumor was confirmed by pathological and histological examination, and the patient met the following criteria for relapsed or refractory B cell hematological tumor:
• Refractory / relapsed B lymphocytic leukemia (1 of the following 4 items can be met):
• i . Recurrence within 6 months of first remission; ii. Primary refractory without complete remission after 2 cycles of standard chemotherapy regimen; iii. No complete remission or recurrence after first-line or multiline salvage chemotherapy; iv. Not eligible for HSCT conditions, abandonment of HSCT, or relapse after HSCT due to conditional limitations.
• Refractory / relapsed B-cell lymphoma (meet the following item 1 of the first 4 items plus item 5):
• i . After four courses of chemotherapy with a standard regimen, tumor shrinkage was less than 50% or disease progression; ii . CR after standard regimen chemotherapy, but relapsed within 6 months; iii.2 or more recurrences after CR; iv . Not suitable for hematopoietic stem cell transplantation, or abandoning HSCT due to conditional restrictions or relapse after hematopoietic stem cell transplantation; v . Subject must have received prior adequate treatment, including at least: a monoclonal antibody against CD 20 and combination chemotherapy containing an anthracycline drug agent.
• The results of FCM or immunohistochemical detection of tumor antigen (CD 19 / CD 22) were positive.
• The estimated survival period is more than 3 months starting from the signing of the informed consent form.
• Good organ function,Meet the following requirements：
• HGB≥70g/L(transfusible)
• Liver and kidney function: creatinine ≤1.5XULN: total bilirubin ≤1.5XULN:ALT and AST≤2.5X ULN
• Cardiopulmonary function: left ventricular ejection fraction \>50%; Blood oxygen saturation \>90%;
• Subjects with the Eastern Cooperative Oncology Group (ECOG) fitness scores of 0 to 2.

You may not qualify if:

• Serious heart insufficiency,LVEF \<50%
• History of severe pulmonary function impairment disease.
• Other malignant tumors in the advanced stage.
• Severe infection or persistent infection that cannot be effectively controlled.
• Combined with severe autoimmune disease or innate immune deficiency.
• Active hepatitis (hepatitis B virus deoxyribonucleic acid \[HBV-DNA 500 IU / ml and abnormal liver function\] or hepatitis C antibody \[HCV-Ab\] positive, HCV-RNA above the lower limit of detection of the analytical method and abnormal liver function).
• Human immunodeficiency virus (HIV) infection or syphilis infection.
• History of severe allergies to biological products (including antibiotics).
• Acute graft-versus-host response (GVHD) allogeneic hematopoietic stem remained one month after immunosuppressant discontinuation.
• Patients who have other serious physical or mental illnesses or abnormalities in laboratory tests that may increase the risk of participating in the clinical trial or interfere with the study results, and who are deemed unsuitable for participation in the clinical trial by the investigator

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Hebei Taihe Chunyu Biotechnology Co., Ltd: collaborator

Study Sites (1)

Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430022, China

RECRUITING

Related Publications (5)

• Frank MJ, Baird JH, Kramer AM, Srinagesh HK, Patel S, Brown AK, Oak JS, Younes SF, Natkunam Y, Hamilton MP, Su YJ, Agarwal N, Chinnasamy H, Egeler E, Mavroukakis S, Feldman SA, Sahaf B, Mackall CL, Muffly L, Miklos DB; CARdinal-22 Investigator group. CD22-directed CAR T-cell therapy for large B-cell lymphomas progressing after CD19-directed CAR T-cell therapy: a dose-finding phase 1 study. Lancet. 2024 Jul 27;404(10450):353-363. doi: 10.1016/S0140-6736(24)00746-3. Epub 2024 Jul 9.

  PMID: 38996463 BACKGROUND

• Spiegel JY, Patel S, Muffly L, Hossain NM, Oak J, Baird JH, Frank MJ, Shiraz P, Sahaf B, Craig J, Iglesias M, Younes S, Natkunam Y, Ozawa MG, Yang E, Tamaresis J, Chinnasamy H, Ehlinger Z, Reynolds W, Lynn R, Rotiroti MC, Gkitsas N, Arai S, Johnston L, Lowsky R, Majzner RG, Meyer E, Negrin RS, Rezvani AR, Sidana S, Shizuru J, Weng WK, Mullins C, Jacob A, Kirsch I, Bazzano M, Zhou J, Mackay S, Bornheimer SJ, Schultz L, Ramakrishna S, Davis KL, Kong KA, Shah NN, Qin H, Fry T, Feldman S, Mackall CL, Miklos DB. CAR T cells with dual targeting of CD19 and CD22 in adult patients with recurrent or refractory B cell malignancies: a phase 1 trial. Nat Med. 2021 Aug;27(8):1419-1431. doi: 10.1038/s41591-021-01436-0. Epub 2021 Jul 26.

  PMID: 34312556 BACKGROUND

• Fry TJ, Shah NN, Orentas RJ, Stetler-Stevenson M, Yuan CM, Ramakrishna S, Wolters P, Martin S, Delbrook C, Yates B, Shalabi H, Fountaine TJ, Shern JF, Majzner RG, Stroncek DF, Sabatino M, Feng Y, Dimitrov DS, Zhang L, Nguyen S, Qin H, Dropulic B, Lee DW, Mackall CL. CD22-targeted CAR T cells induce remission in B-ALL that is naive or resistant to CD19-targeted CAR immunotherapy. Nat Med. 2018 Jan;24(1):20-28. doi: 10.1038/nm.4441. Epub 2017 Nov 20.

  PMID: 29155426 BACKGROUND

• 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

• Dual CD19/CD22 CAR T Cells Show Feasibility in Pediatric/Young Adult B-ALL. Cancer Discov. 2021 Dec 1;11(12):2958. doi: 10.1158/2159-8290.CD-RW2021-150.

  PMID: 34686527 BACKGROUND

MeSH Terms

Conditions

Burkitt Lymphoma; Lymphoma; Recurrence

Condition Hierarchy (Ancestors)

Epstein-Barr Virus Infections; Herpesviridae Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Lymphoma, B-Cell; Lymphoma, Non-Hodgkin; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Hemic and Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Heng Mei, M.D., Ph.D

  Union Hospital, Tongji Medical College, Huazhong University of Science and Technology

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Heng Mei, M.D., Ph.D

CONTACT

027-8572600; hmei@hust.edu.cn

Yun Kang

CONTACT

17362995329; cloudykang@hust.edu.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Proferssor, Cheif Doctor

Study Record Dates

• First Submitted: December 5, 2024
• First Posted: December 16, 2024
• Study Start: November 4, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: December 16, 2024

Record last verified: 2024-12

Locations

CN (1)