Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma

NCT03207178 | Unknown Phase 1 DMC

• 1 other identifier: LYCT-1701
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Cluster of differentiation antigen 19(CD19) specifically presents in B lymphocyte cell lines steadily,while not in most normal tissue,including pluripotent hematopoietic stem cells.Cluster of differentiation antigen 20(CD20) presents in 90% of B-cell lymphomas.CD19 antigen is a well-established target for B-cell lymphomas treatment as well as CD20 antigen.Both CD19-targeting CAR T Cells and CD20-targeting CAR T Cells can be used as adoptive cellular immunotherapies for B-cell lymphomas.Though two kinds of single target treatments were proved can induce recession of B-cell lymphomas, the risk of cancer cells to escape and tumor recurrence are still existed. There are no report about combination transfer of two kinds of single target treatments.This research aimed emphasis on safety and therapeutic efficacy evaluation,as well as if combination transfer can decrease recurrence rate.

Conditions

Recurrent or Refractory B Cell Malignancy

Outcome Measures

Primary Outcomes (1)

• Overall complete remission rate

  The complete remission rate will be evaluated by routine methods.

  Half a year

Secondary Outcomes (6)

• The initial effect time

  1 year

• The one-year survival rate

  1 year

• The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity)

  1 month

• The time to disease progression

  1 year

• The one-year recurrence

  1 year

Study Arms (1)

Mixed CD19/CD20 CAR-T Transfer

EXPERIMENTAL

Subjects with CD19+/CD20+ B-cell lymphomas will be infused with CD19-targeting CAR T Cells and CD20-targeting CAR T Cells in one time or in parts

Biological: Mixed CD19/CD20 CAR-T Transfer

Interventions

Mixed CD19/CD20 CAR-T Transfer BIOLOGICAL

Autologous CD19 CAR-T cells and CD20 CAR-T cells with average 1-5\*10\^6 cells/kg body weight,separately.

Mixed CD19/CD20 CAR-T Transfer

Eligibility Criteria

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

You may qualify if:

• Years to 70 Years, Male and female
• Survival time\>12 weeks
• B cell lymphomas diagnosed by Physical examination,pathological examination,Laboratory tests and imaging tests
• Chemotherapy failure or recurrent B cell lymphomas
• Creatinine\< 2.5mg/dl
• Glutamic-pyruvic transaminase, glutamic oxalacetic transaminase\< 3 fold of normal level
• Bilirubin\<2.0mg/dl
• Karnofsky Performance Status\>50% at the time of screening
• Adequate pulmonary, renal, hepatic, and cardiac function
• Fail in autologous or allogenic haemopoietic stem cell transplantation
• Free of leukocytes removal contraindications
• Voluntarily join CAR-T clinical trial
• Understand and sign written informed consent

You may not qualify if:

• Pregnant or nursing women or women with pregnancy plan in half a year
• Any infectious disease (HIV, active tuberculosis, ect.)
• Active hepatitis B, active hepatitis C infection
• Feasibility assessment proves that the efficiency of transduction of lymphocyte is below 10% or the lymphocyte amplification is below 5 fold with the costimulation of cluster of differentiation 3(CD 3)and cluster of differentiation 8(CD 8)
• Abnormal vital signs or cannot cooperate with the inspectors
• mental or psychological disease cannot cooperate with treatment and curative effect evaluation
• Highly allergic constitution or history of severe allergies, especially allergy to interleukin-2(IL-2)
• General infection or local severe infection, or other infection that is not controlled
• Dysfunction in lung, heart, kidney and brain
• Severe autoimmune diseases
• Other symptoms that are not applicable for CAR-T

Sponsors & Collaborators

• Shanghai Longyao Biotechnology Inc., Ltd.: lead
• Xuzhou Medical University: collaborator
• Shanghai Jiao Tong University School of Medicine: collaborator

Study Sites (1)

Shanghai Longyao Biotechnology Inc., Ltd.

Shanghai, Jingan, 200072, China

RECRUITING

Related Publications (6)

• Wang Y, Zhang WY, Han QW, Liu Y, Dai HR, Guo YL, Bo J, Fan H, Zhang Y, Zhang YJ, Chen MX, Feng KC, Wang QS, Fu XB, Han WD. Effective response and delayed toxicities of refractory advanced diffuse large B-cell lymphoma treated by CD20-directed chimeric antigen receptor-modified T cells. Clin Immunol. 2014 Dec;155(2):160-75. doi: 10.1016/j.clim.2014.10.002. Epub 2014 Oct 16.

  PMID: 25444722 BACKGROUND

• Witkowska M, Smolewski P. Emerging immunotherapy and strategies directly targeting B cells for the treatment of diffuse large B-cell lymphoma. Immunotherapy. 2015;7(1):37-46. doi: 10.2217/imt.14.93.

  PMID: 25572478 BACKGROUND

• Brudno JN, Somerville RP, Shi V, Rose JJ, Halverson DC, Fowler DH, Gea-Banacloche JC, Pavletic SZ, Hickstein DD, Lu TL, Feldman SA, Iwamoto AT, Kurlander R, Maric I, Goy A, Hansen BG, Wilder JS, Blacklock-Schuver B, Hakim FT, Rosenberg SA, Gress RE, Kochenderfer JN. Allogeneic T Cells That Express an Anti-CD19 Chimeric Antigen Receptor Induce Remissions of B-Cell Malignancies That Progress After Allogeneic Hematopoietic Stem-Cell Transplantation Without Causing Graft-Versus-Host Disease. J Clin Oncol. 2016 Apr 1;34(10):1112-21. doi: 10.1200/JCO.2015.64.5929. Epub 2016 Jan 25.

  PMID: 26811520 BACKGROUND

• Hay KA, Turtle CJ. Chimeric Antigen Receptor (CAR) T Cells: Lessons Learned from Targeting of CD19 in B-Cell Malignancies. Drugs. 2017 Mar;77(3):237-245. doi: 10.1007/s40265-017-0690-8.

  PMID: 28110394 BACKGROUND

• Ernst M, Oeser A, Besiroglu B, Caro-Valenzuela J, Abd El Aziz M, Monsef I, Borchmann P, Estcourt LJ, Skoetz N, Goldkuhle M. Chimeric antigen receptor (CAR) T-cell therapy for people with relapsed or refractory diffuse large B-cell lymphoma. Cochrane Database Syst Rev. 2021 Sep 13;9(9):CD013365. doi: 10.1002/14651858.CD013365.pub2.

  PMID: 34515338 DERIVED

• Sang W, Shi M, Yang J, Cao J, Xu L, Yan D, Yao M, Liu H, Li W, Zhang B, Sun K, Song X, Sun C, Jiao J, Qin Y, Sang T, Ma Y, Wu M, Gao X, Cheng H, Yan Z, Li D, Sun H, Zhu F, Wang Y, Zeng L, Li Z, Zheng J, Xu K. Phase II trial of co-administration of CD19- and CD20-targeted chimeric antigen receptor T cells for relapsed and refractory diffuse large B cell lymphoma. Cancer Med. 2020 Aug;9(16):5827-5838. doi: 10.1002/cam4.3259. Epub 2020 Jul 1.

  PMID: 32608579 DERIVED

MeSH Terms

Conditions

Recurrence

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Shengqin Ye, M.D.

  Shanghai Longyao Biotechnology Inc., Ltd.

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Xin Wang, M.D.

CONTACT

185-1602-2625; wangxin928@163.com

Jiang Cao, Ph.D.

CONTACT

159-5146-8263; zimu05067@163.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 23, 2017
• First Posted: July 2, 2017
• Study Start: March 1, 2017
• Primary Completion: February 28, 2019
• Study Completion: February 28, 2020
• Last Updated: July 2, 2017

Record last verified: 2017-06

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)