Anti-CD19/CD22 Bispecific CAR-T Cell Therapy for CD19-positive ALL

NCT04303520 | Unknown Phase 1 DMC

• 1 other identifier: Anti-CD19/CD22 CAR-T
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to study the feasibility and efficacy of anti-CD19/CD22 bispecific chimeric antigen receptors (CARs) T cell therapy for CD19-positive Acute Lymphoblastic Leukemia.

Conditions

CD19-positive ALL

Outcome Measures

Primary Outcomes (1)

• Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

  Safety measured by occurrence of study related adverse effects defined by NCI CTCAE 4.0

  6 months

Secondary Outcomes (3)

• Overall complete remission rate defined by the standard response criteria for malignant lymphoma for each arm

  8 weeks

• Duration of CAR-positive T cells in circulation

  6 months

• Total number of CAR-positive T cells infiltrated into lymphoma tissue

  6 months

Study Arms (1)

anti-CD19/CD22 CAR-T cells

EXPERIMENTAL

Administration with anti-CD19/CD22 CAR-T cells in the CD19-positive ALL patients

Biological: anti-CD19/CD22 CAR-T cells; Drug: Fludarabine; Drug: Cyclophosphamide

Interventions

anti-CD19/CD22 CAR-T cells BIOLOGICAL

Retroviral vector-transduced autologous T cells to express anti-CD19 and anti-CD22 CARs

anti-CD19/CD22 CAR-T cells

Fludarabine DRUG

30mg/m2/d

anti-CD19/CD22 CAR-T cells

Cyclophosphamide DRUG

500mg/m2/d

anti-CD19/CD22 CAR-T cells

Eligibility Criteria

• Age: 13 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Years to 70 Years, Male and female;
• Expected survival \> 12 weeks;
• Clinical performance status of ECOG score 0-2;
• Histologically confirmed as CD19-positive lymphoma and who meet one of the following conditions:
• Patients received at least 2 prior combination chemotherapy regimens (not including single agent monoclonal antibody therapy) and fail to achieve CR; or have disease recurrence; or not eligible for allogeneic stem cell transplantation; or disease responding or stable after most recent therapy but refused further treatment;
• Disease recurrence after stem cell transplantation.
• Accessible to intravenous injection, and no white blood cell collection contraindications
• Patients who meet the following conditions:
• Creatinine \< 2.5 mmol/l;
• Cardiac ejection fraction\>50%, no pericardial effusion and no pleural effusion (ECHO examination);
• Baseline oxygen saturation\>92%;
• Total bilirubin≤1.5xULN;
• ALT/AST≤2.5x normal.
• Able to understand and sign the Informed Consent Document.

You may not qualify if:

• Accompanied by other malignant tumor
• Active hepatitis B, hepatitis C, syphilis, HIV infection
• Suffering severe cardiovascular or respiratory disease
• Any other diseases could affect the outcome of this trial
• Any affairs could affect the safety of the subjects or outcome of this trial
• Pregnant or lactating women, or patients who plan to be pregnancy during or after treatment
• Occurrence of infection uncontrolled or requiring systemic treatment 14 days prior to assignment
• Patients who are accounted by researchers to be not appropriate for this test
• Received CAR-T treatment or other gene therapies before assignment
• Patients with symptoms of central nervous system
• Subject suffering disease affects the understanding of informed consent or comply with study protocol.

Sponsors & Collaborators

• The Second Affiliated Hospital of Henan University of Traditional Chinese Medicine: lead
• Hrain Biotechnology Co., Ltd.: collaborator
• First Affiliated Hospital of Wenzhou Medical University: collaborator
• Second Affiliated Hospital of Nanchang University: collaborator

Study Sites (1)

Henan Province of TCM

Zhengzhou, Henan, China

RECRUITING

Related Publications (14)

• Litzow MR. Hematology clinic. Acute lymphoblastic leukemia. Hematology. 2014 Jun;19(4):246-7. doi: 10.1179/1024533214Z.000000000281. No abstract available.

  PMID: 24856441 BACKGROUND

• Gokbuget N, Stanze D, Beck J, Diedrich H, Horst HA, Huttmann A, Kobbe G, Kreuzer KA, Leimer L, Reichle A, Schaich M, Schwartz S, Serve H, Starck M, Stelljes M, Stuhlmann R, Viardot A, Wendelin K, Freund M, Hoelzer D; German Multicenter Study Group for Adult Acute Lymphoblastic Leukemia. Outcome of relapsed adult lymphoblastic leukemia depends on response to salvage chemotherapy, prognostic factors, and performance of stem cell transplantation. Blood. 2012 Sep 6;120(10):2032-41. doi: 10.1182/blood-2011-12-399287. Epub 2012 Apr 4.

  PMID: 22493293 BACKGROUND

• Philip T, Guglielmi C, Hagenbeek A, Somers R, Van der Lelie H, Bron D, Sonneveld P, Gisselbrecht C, Cahn JY, Harousseau JL, et al. Autologous bone marrow transplantation as compared with salvage chemotherapy in relapses of chemotherapy-sensitive non-Hodgkin's lymphoma. N Engl J Med. 1995 Dec 7;333(23):1540-5. doi: 10.1056/NEJM199512073332305.

  PMID: 7477169 BACKGROUND

• Nguyen K, Devidas M, Cheng SC, La M, Raetz EA, Carroll WL, Winick NJ, Hunger SP, Gaynon PS, Loh ML; Children's Oncology Group. Factors influencing survival after relapse from acute lymphoblastic leukemia: a Children's Oncology Group study. Leukemia. 2008 Dec;22(12):2142-50. doi: 10.1038/leu.2008.251. Epub 2008 Sep 25.

  PMID: 18818707 BACKGROUND

• Bhojwani D, Pui CH. Relapsed childhood acute lymphoblastic leukaemia. Lancet Oncol. 2013 May;14(6):e205-17. doi: 10.1016/S1470-2045(12)70580-6.

  PMID: 23639321 BACKGROUND

• Raetz EA, Bhatla T. Where do we stand in the treatment of relapsed acute lymphoblastic leukemia? Hematology Am Soc Hematol Educ Program. 2012;2012:129-36. doi: 10.1182/asheducation-2012.1.129.

  PMID: 23233571 BACKGROUND

• Uckun FM, Jaszcz W, Ambrus JL, Fauci AS, Gajl-Peczalska K, Song CW, Wick MR, Myers DE, Waddick K, Ledbetter JA. Detailed studies on expression and function of CD19 surface determinant by using B43 monoclonal antibody and the clinical potential of anti-CD19 immunotoxins. Blood. 1988 Jan;71(1):13-29.

  PMID: 3257143 BACKGROUND

• Onea AS, Jazirehi AR. CD19 chimeric antigen receptor (CD19 CAR)-redirected adoptive T-cell immunotherapy for the treatment of relapsed or refractory B-cell Non-Hodgkin's Lymphomas. Am J Cancer Res. 2016 Jan 15;6(2):403-24. eCollection 2016.

  PMID: 27186412 BACKGROUND

• Ramos CA, Heslop HE, Brenner MK. CAR-T Cell Therapy for Lymphoma. Annu Rev Med. 2016;67:165-83. doi: 10.1146/annurev-med-051914-021702. Epub 2015 Aug 26.

  PMID: 26332003 BACKGROUND

• Gardner RA, Finney O, Annesley C, Brakke H, Summers C, Leger K, Bleakley M, Brown C, Mgebroff S, Kelly-Spratt KS, Hoglund V, Lindgren C, Oron AP, Li D, Riddell SR, Park JR, Jensen MC. Intent-to-treat leukemia remission by CD19 CAR T cells of defined formulation and dose in children and young adults. Blood. 2017 Jun 22;129(25):3322-3331. doi: 10.1182/blood-2017-02-769208. Epub 2017 Apr 13.

  PMID: 28408462 BACKGROUND

• Turtle CJ, Hanafi LA, Berger C, Gooley TA, Cherian S, Hudecek M, Sommermeyer D, Melville K, Pender B, Budiarto TM, Robinson E, Steevens NN, Chaney C, Soma L, Chen X, Yeung C, Wood B, Li D, Cao J, Heimfeld S, Jensen MC, Riddell SR, Maloney DG. CD19 CAR-T cells of defined CD4+:CD8+ composition in adult B cell ALL patients. J Clin Invest. 2016 Jun 1;126(6):2123-38. doi: 10.1172/JCI85309. Epub 2016 Apr 25.

  PMID: 27111235 BACKGROUND

• Park JH, Geyer MB, Brentjens RJ. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood. 2016 Jun 30;127(26):3312-20. doi: 10.1182/blood-2016-02-629063. Epub 2016 May 20.

  PMID: 27207800 BACKGROUND

• Lee DW, Kochenderfer JN, Stetler-Stevenson M, Cui YK, Delbrook C, Feldman SA, Fry TJ, Orentas R, Sabatino M, Shah NN, Steinberg SM, Stroncek D, Tschernia N, Yuan C, Zhang H, Zhang L, Rosenberg SA, Wayne AS, Mackall CL. T cells expressing CD19 chimeric antigen receptors for acute lymphoblastic leukaemia in children and young adults: a phase 1 dose-escalation trial. Lancet. 2015 Feb 7;385(9967):517-528. doi: 10.1016/S0140-6736(14)61403-3. Epub 2014 Oct 13.

  PMID: 25319501 BACKGROUND

• Ma Q, Wei R, Wang Q, Jiang S, Wu Y, Min C, Guo S, Zhang Y, Sun X, Wu H, Sun X, Xiang F, Xiao M, Cheng Z. A bi-specific CAR-T cell therapy targeting CD19 and CD22 in relapsed or refractory B-ALL. Clin Exp Med. 2025 Jul 28;25(1):264. doi: 10.1007/s10238-025-01637-8.

  PMID: 40719826 DERIVED

MeSH Terms

Interventions

fludarabine; Cyclophosphamide

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

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: March 9, 2020
• First Posted: March 11, 2020
• Study Start: May 3, 2018
• Primary Completion: September 1, 2020
• Study Completion: February 1, 2021
• Last Updated: March 11, 2020

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will share

Locations

CN (1)