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

Tracking Information
First Submitted Date ICMJE	June 23, 2017
First Posted Date ICMJE	July 2, 2017
Last Update Posted Date	July 2, 2017
Actual Study Start Date ICMJE	March 1, 2017
Estimated Primary Completion Date	February 28, 2019 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: June 29, 2017)	Overall complete remission rate [ Time Frame: Half a year ]; The complete remission rate will be evaluated by routine methods.
Original Primary Outcome Measures ICMJE	Same as current
Change History	No Changes Posted
Current Secondary Outcome Measures ICMJE; (submitted: June 29, 2017)	The initial effect time [ Time Frame: 1 year ]The initial effect time will be recorded.; The one-year survival rate [ Time Frame: 1 year ]The one-year survival rate will be recorded.; The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity) [ Time Frame: 1 month ]Number of participants with treatment-related adverse events as assessed by CTCAE v4.0.; The time to disease progression [ Time Frame: 1 year ]The time to disease progression will be counted after complete remission.; The one-year recurrence [ Time Frame: 1 year ]The one-year recurrence will be counted after complete remission.; The life quality improvement [ Time Frame: 1 year ]The life quality improvement will be evaluated by appetite,sleep,pain and mental state.
Original Secondary Outcome Measures ICMJE	Same as current
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Sequential Infusion of Anti-CD19 and Anti-CD20 CAR-T Cells Against Relapsed and Refractory B-cell Lymphoma
Official Title ICMJE	Sequential Infusion of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor(CAR) T Cells Against Relapsed and Refractory B-cell Lymphoma
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.
Study Type ICMJE	Interventional
Study Phase	Phase 1; Phase 2
Study Design ICMJE	Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Recurrent or Refractory B Cell Malignancy
Intervention ICMJE	Biological: 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.
Study Arms	Experimental: 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; Intervention: Biological: Mixed CD19/CD20 CAR-T Transfer
Publications *	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.; 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. Review.; 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.; 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. Review.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Recruiting
Estimated Enrollment ICMJE; (submitted: June 29, 2017)	20
Original Estimated Enrollment ICMJE	Same as current
Estimated Study Completion Date	February 28, 2020
Estimated Primary Completion Date	February 28, 2019 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 70 Years (Adult, Older Adult)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact: Xin Wang, M.D. 185-1602-2625 ext +86 wangxin928@163.com Contact: Jiang Cao, Ph.D. 159-5146-8263 ext +86 zimu05067@163.com
Listed Location Countries ICMJE	China
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT03207178
Other Study ID Numbers ICMJE	LYCT-1701
Has Data Monitoring Committee	Yes
U.S. FDA-regulated Product	Studies a U.S. FDA-regulated Drug Product: No Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement	Plan to Share IPD: No
Responsible Party	Shanghai Longyao Biotechnology Inc., Ltd.
Study Sponsor ICMJE	Shanghai Longyao Biotechnology Inc., Ltd.
Collaborators ICMJE	Xuzhou Medical University; Shanghai Jiao Tong University School of Medicine
Investigators ICMJE	Principal Investigator: Shengqin Ye, M.D. Shanghai Longyao Biotechnology Inc., Ltd.
PRS Account	Shanghai Longyao Biotechnology Inc., Ltd.
Verification Date	June 2017
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP