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

NCT ID: NCT03207178

Last Updated: 2017-07-02

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-01
• Study Completion Date: 2020-02-28

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.

Detailed Description

To determine:

Primary Outcome Measure:

The Overall complete remission rate and one-year survival rate of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is superior to or at least not worse than two kinds of single target treatments in the treatment of CD19+/CD20+ B-cell lymphomas.

The risk of cancer recurrence in a year of combination transfer of CD19-targeting CAR T Cells and CD20-targeting CAR T Cells is inferior to two kinds of single target treatments.

Secondary Outcome Measures:

Evaluate the initial effect time, time to disease progression, and life quality improvement of combination transfer compare to single target treatments.

Evaluate the safety and tolerability of combination transfer compare to single target treatments by observation of high fever duration in patients and testing related cell factor level in peripheral blood.

Conditions

Recurrent or Refractory B Cell Malignancy

Study Design

• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Mixed CD19/CD20 CAR-T Transfer

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

Group Type: EXPERIMENTAL

Mixed CD19/CD20 CAR-T Transfer

Intervention Type: BIOLOGICAL

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

Interventions

Mixed CD19/CD20 CAR-T Transfer

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

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• 18 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

Exclusion Criteria

• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Xuzhou Medical University

OTHER

Sponsor Role: collaborator

Shanghai Jiao Tong University School of Medicine

OTHER

Sponsor Role: collaborator

Shanghai Longyao Biotechnology Inc., Ltd.

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shengqin Ye, M.D.

Role: PRINCIPAL_INVESTIGATOR

Shanghai Longyao Biotechnology Inc., Ltd.

Locations

Shanghai Longyao Biotechnology Inc., Ltd.

Shanghai, Jingan, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xin Wang, M.D.

Role: CONTACT

wangxin928@163.com

185-1602-2625 ext. +86

Jiang Cao, Ph.D.

Role: CONTACT

zimu05067@163.com

159-5146-8263 ext. +86

Facility Contacts

Wang Xin, M.D.

Role: primary

wangxin928@163.com

185-1602-2625 ext. +86

References

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.

Reference Type: BACKGROUND

PMID: 25444722 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25572478 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26811520 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28110394 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34515338 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32608579 (View on PubMed)

Other Identifiers

LYCT-1701

Identifier Type: -

Identifier Source: org_study_id