Clinical Study of Redirected Autologous T Cells With a Chimeric Antigen Receptor in Patients With Malignant Tumors
1 other identifier
interventional
18
1 country
1
Brief Summary
A single arm, open-label pilot study is designed to determine the safety, efficacy and cytokinetics of CAR T cells in patients with malignant tumors with positive antigen targets. CAR T cells are genetically engineered to express single-chain variable fragment (scFv) targeting indication-specific antigens. The investigational CAR T cells and proposed indications are as follows: CAR-CD19 T cells for B cell leukaemia/lymphoma; CAR-BCMA T cells for myeloma; CAR-GPC3 T cell for hepatocellular carcinoma; CAR-CLD18 T cells for pancreatic carcinoma and adenocarcinoma of esophagogastric junction.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Dec 2017
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 26, 2017
CompletedFirst Posted
Study publicly available on registry
October 5, 2017
CompletedStudy Start
First participant enrolled
December 29, 2017
CompletedPrimary Completion
Last participant's last visit for primary outcome
December 12, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 12, 2023
CompletedOctober 8, 2020
October 1, 2020
3 years
September 26, 2017
October 5, 2020
Conditions
Outcome Measures
Primary Outcomes (1)
Number of participants with CRA T-related adverse events as assessed by CTCAE v4.03
Number of participants with study related adverse events which are defined as laboratory toxicities and clinical events that are possible, likely or definitely related to study treatment at any time from the infusion until week 24, including infusion related toxicity and any toxicity possibly related to CAR T cells.
24 weeks
Secondary Outcomes (1)
Engraftment
2 years
Other Outcomes (8)
Progression-free Survival (PFS)
5 years for BCMA, 2 years for GPC3, CD19 and Claudin 18.2
Time to Tumor Progression (TTP)
5 years for BCMA, 2 years for GPC3, CD19 and Claudin 18.2
Disease Control Rate (DCR)
2 years
- +5 more other outcomes
Study Arms (1)
CAR T cell
EXPERIMENTALIn this study, autologous T cells transduced with a chimeric antigen receptor are used to treat patients with malignant tumors: CAR-CD19 T cell is for the treatment of B-cell Leukaemia/Lymphoma; CAR-BCMA T cell is for the treatment of Myeloma; CAR-GPC3 T cell is for the treatment of Hepatocellular Carcinoma; CAR-CLD18 T cell is for the treatment of Pancreatic Carcinoma and Adenocarcinoma of Esophagogastric Junction. Route of administration: Intravenous injection. Lymphodepletion conditioning: Lymphodepletion will be conducted several days prior to CAR T cell infusion, which may improve in vivo cell count and survival of T cells. A combination of fludarabine and cyclophosphamide will be used for lymphodepletion.
Interventions
Self-controlled dose escalation and classic "3+3" dose escalation will be applied.
Self-controlled dose escalation and classic "3+3" dose escalation will be applied.
Self-controlled dose escalation and classic "3+3" dose escalation will be applied.
Self-controlled dose escalation and classic "3+3" dose escalation will be applied.
Eligibility Criteria
You may qualify if:
- I. B-Cell Lymphoblastic Leukaemia/Lymphoma
- Patients aged between 18 \~ 65 with B-cell lymphoblastic leukaemia/lymphoma.
- CD19-positive B-cell lymphoblastic leukaemia/lymphoma.
- Patients with unmet medical needs for which there are no effective therapies known at this time:
- A. Relapsed or Refractory (r/r) Acute Lymphoblastic Leukemia (ALL)
- Patients with r/r ALL for whom hematopoietic stem cell transplantation (HSCT) is not suitable due to following reasons:
- Age;
- Excessive tumor burden or concomitant disease;
- No donor available.
- B. CD19-positive Follicular Lymphoma:
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy;
- Less than 6 months between last chemotherapy and disease progression (most recent progression free interval \< 6 months);
- Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.).
- C. Chronic Lymphocytic Leukemia (CLL)
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy);
- +76 more criteria
You may not qualify if:
- Patients with any of the following conditions are not eligible for this study.
- Transduction of target lymphocytes \< 10%, expansion in response to αCD3/CD28 costimulation \< 5-fold.
- Pregnant or lactating women.
- HIV positive, or HCV positive
- Uncontrolled active infection, including active tuberculosis and HBV DNA copies ≥ 1×10\^3 copies/mL.
- Allergic to immunotherapies and related drugs.
- Patients with heart disease for which treatment is needed or with poorly controlled hypertension.
- Hyponatremia: serum sodium level \< 125 mmol/L.
- Baseline serum potassium \< 3.5 mmol/L (taking potassium supplements before participating in the study to raise potassium level is acceptable).
- Previous treatment with chemoradiotherapy, immunotherapy and tumor-targeting drug conducted 2 weeks prior to participation in this study or blood collection.
- Patients have undertaken immunosuppressor for graft-versus-host disease (GVHD) within 4 weeks before participation in this study or blood collection, or the patient is diagnosed with acute or chronic GVHD.
- Other severe disease that may restrain patients from participating in this study (e.g. diabetes, severe cardiac dysfunction, myocardial infarction or unstable arrhythmias or unstable angina in recent 6 months, gastric ulcer, active autoimmune disease, etc.).
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Kang YUlead
- CARsgen Therapeutics Co., Ltd.collaborator
Study Sites (1)
First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, 325000, China
Related Publications (1)
Dong R, Jiang S, Chen Y, Ma Y, Sun L, Xing C, Zhang S, Yu K. Prognostic Significance of Cytokine Release Syndrome in B Cell Hematological Malignancies Patients After Chimeric Antigen Receptor T Cell Therapy. J Interferon Cytokine Res. 2021 Dec;41(12):469-476. doi: 10.1089/jir.2021.0057.
PMID: 34935483DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Mengtao Zhou, MD
First Affiliated Hospital of Wenzhou Medical University
- PRINCIPAL INVESTIGATOR
Kang Yu, MD
First Affiliated Hospital of Wenzhou Medical University
- PRINCIPAL INVESTIGATOR
Songfu Jiang, MD
First Affiliated Hospital of Wenzhou Medical University
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Head of Department of Hematology
Study Record Dates
First Submitted
September 26, 2017
First Posted
October 5, 2017
Study Start
December 29, 2017
Primary Completion
December 12, 2020
Study Completion
December 12, 2023
Last Updated
October 8, 2020
Record last verified: 2020-10
Data Sharing
- IPD Sharing
- Will not share