Recurrent or Refractory B Cell Malignancy Clinical Trial
Official title:
Sequential Infusion of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor(CAR) T Cells Against Relapsed and Refractory B-cell Lymphoma
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.
| Status | Recruiting |
| Enrollment | 20 |
| Est. completion date | February 28, 2020 |
| Est. primary completion date | February 28, 2019 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 70 Years |
| Eligibility |
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 |
| Country | Name | City | State |
|---|---|---|---|
| China | Shanghai Longyao Biotechnology Inc., Ltd. | Shanghai | Jingan |
| Lead Sponsor | Collaborator |
|---|---|
| Shanghai Longyao Biotechnology Inc., Ltd. | Shanghai Jiao Tong University School of Medicine, Xuzhou Medical University |
China,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Overall complete remission rate | The complete remission rate will be evaluated by routine methods. | Half a year | |
| Secondary | The initial effect time | The initial effect time will be recorded. | 1 year | |
| Secondary | The one-year survival rate | The one-year survival rate will be recorded. | 1 year | |
| Secondary | The safety and the tolerability(incidence of treatment-emergent adverse events defined as dose-limited toxicity) | Number of participants with treatment-related adverse events as assessed by CTCAE v4.0. | 1 month | |
| Secondary | The time to disease progression | The time to disease progression will be counted after complete remission. | 1 year | |
| Secondary | The one-year recurrence | The one-year recurrence will be counted after complete remission. | 1 year | |
| Secondary | The life quality improvement | The life quality improvement will be evaluated by appetite,sleep,pain and mental state. | 1 year |
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Recruiting |
NCT02794961 -
CD22 Targeting CAR-T Therapy Against B Cell Hematological Malignancies
|
Phase 1/Phase 2 |