Status:
UNKNOWN
Clinical Study of Redirected Autologous T Cells With a Chimeric Antigen Receptor in Patients With Malignant Tumors
Lead Sponsor:
Kang YU
Collaborating Sponsors:
CARsgen Therapeutics Co., Ltd.
Conditions:
B Cell Lymphoma
B Cell Leukemia
Eligibility:
All Genders
18-75 years
Phase:
NA
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 gen...
Detailed Description
This study is designed to determine the safety, tolerability and engraftment potential of lentivirus-transduced CAR T cells in patients with malignant tumors. Primary objectives: 1. Determine the sa...
Eligibility Criteria
Inclusion
- 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);
- Less than6 months between last chemotherapy and disease progression (most recent progression free interval \< 6 months);
- Not eligible or appropriate for conventional HSCT.
- Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.).
- D. Mantle Cell Lymphoma
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy);
- Disease progression after most recent systemic therapy (chemotherapy, MoAb, etc.)；
- Relapsed after prior autologous SCT.
- E. B-Cell Prolymphocytic Leukemia (PLL)
- Relapsed or residual disease after at least 1 prior therapy and not eligible for HSCT.
- F. CD19-positive Diffuse Large B Cell Lymphoma
- At least 2 prior chemotherapy regimens (not including single agent monoclonal antibody (Rituxan) therapy;
- Stage III-IV disease.
- Less than 6 months between last chemotherapy and disease progression (most recent progression free interval \< 6 months);
- Disease progression after most recent therapy (chemotherapy, MoAb, etc.).
- Expected survival \> 12 weeks.
- At least one measurable lesion (≥ 10 mm) for patients with lymphoma.
- ECOG scores 0-1, or KPS scores \> 70.
- Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
- WBC ≥ 2.5×10\^9/L; PLT ≥ 60×10\^9/L (for patients with lymphoma); Hb ≥ 9.0 g/dL; LY ≥ 0.47×10\^9/L; LY% ≥ 15%.
- Serum Alb ≥ 30 g/L.
- Serum creatinine ≤ 1.5 ULN.
- ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN.
- Serum total bilirubin ≤ 1.5 ULN. The above lab results should not include those obtained from continuous supportive treatment that is ongoing.
- II. Myeloma
- Patients aged between 18 \~ 75 with relapsed or refractory multiple myeloma.
- Bone marrow sample is confirmed as BCMA-positive by flow cytometry or pathological examination.
- Patients with relapsed or refractory malignancies who meet the following descriptions:
- Curative efficacy is little or disease progressed after 2 courses of standard treatment regimen;
- Disease relapsed after chemotherapy or HSCT. Curative efficacy is little or disease progressed after 2 courses of original treatment regimen;
- More than 30 days between last treatment and disease progression;
- There is no indication for HSCT at present;
- Disease progression is defined as per "Chinese Guidelines for Diagnosis and Treatment of Multiple Myeloma (Version 2015)". One or more of the following conditions should be met:
- i. Serum M-protein increases ≥ 25% (absolute increase should be ≥ 5 g/L). If serum M protein is ≥ 50 g/L at baseline, increase of serum M protein can be ≥ 10 g/L; ii. Urine M-protein increases ≥ 25% (absolute increase should be ≥ 200 mg/24 h); iii. If the serum and urine M-protein are not detectable, a ≥ 25% increase in the difference between involved and uninvolved FLC levels is required (absolute increase should be ≥ 100 mg/L); iv. Bone marrow plasma cell percentage increases ≥ 25% (absolute increase should be ≥ 10%); v. Size of existing bone lesions or soft tissue plasmacytomas increased by ≥ 25%, or development of new lytic bone lesions or oft tissue plasmacytomas; vi. Development of hypercalcemia that can be attributed to plasma cell proliferative disorder (corrected calcium is \> 2.8 mmol/L or 11.5 mg/dL).
- Expected survival \> 12 weeks.
- Disease is measurable, and at least one of the following conditions should be satisfied:
- Serum M-protein is ≥ 10 g/L;
- 24-hour urine M-protein is ≥ 200 mg;
- Serum FLC is ≥ 5 mg/dL;
- Plasmacytomas that can be measured or evaluated by imaging;
- Bone marrow plasma cell percentage is ≥ 20%.
- ECOG scores 0 - 1 or CCI scores ≤ 2.
- Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
- WBC ≥ 1.5×10\^9/L; PLT ≥ 45×10\^9/L; Hb ≥ 9.0 g/dL.
- Serum creatinine ≤ 1.5 ULN.
- ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN. The above lab results should not include those obtained from continuous supportive treatment that is ongoing.
- III. Hepatocellular Carcinoma (HCC)
- Patients aged 18 \~ 70 with refractory hepatocellular carcinoma.
- Patients with HCC that cannot be eradicated by resection who have received ablation or resection in the last 4 to 12 weeks.
- IHC testing confirmed as GPC3-positive HCC.
- Expected survival \> 12 weeks.
- At least one measurable lesion (≥ 10 mm).
- Cirrhosis of the liver: Child-Pugh Class A, or Child-Pugh Class B scored at 7.
- ECOG scores 0 - 1 or KPS scores \> 70.
- Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
- Hematology:
- WBC ≥ 2.5×10\^9/L; PLT ≥ 60×10\^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.0×10\^9/L; LY ≥ 0.4×10\^9/L.
- Blood Chemistry:
- Serum Alb ≥ 30 g/L; Serum lipase and serum amylase \< 1.5 ULN; Serum creatinine ≤ 1.5 ULN; ALT ≤ 5 ULN; AST ≤ 5 ULN; Serum total bilirubin ≤ 2.5 ULN.
- Coagulation Test:
- Prothrombin time is at most 4 seconds longer than normal value.
- Able to understand and sign the informed consent. All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment.
- IV. Pancreatic Carcinoma and Adenocarcinoma of Esophagogastric Junction
- Patients aged 18 \~ 70 with pathologically confirmed advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction.
- IHC testing confirmed as Claudin18.2 positive.
- Patients with advanced pancreatic carcinoma and adenocarcinoma of esophagogastric junction that cannot be eradicated by resection.
- Expected survival after first dose of study drug \> 12 weeks.
- At least one measurable lesion (≥ 10 mm) available for imaging assessment.
- ECOG scores 0 - 1.
- Adequate venous access for apheresis and venous blood sampling, and no other contraindications for leukapheresis.
- WBC ≥ 2.5×10\^9/L; PLT ≥ 100×10\^9/L; Hb ≥ 9.0 g/dL; MID ≥ 1.5×10\^9/L; LY ≥ 0.47×10\^9/L; LY% ≥ 15%.
- Serum Alb ≥ 30 g/L.
- Serum lipase and serum amylase \< 1.5 ULN.
- Serum creatinine ≤ 1.5 ULN.
- ALT ≤ 2.5 ULN; AST ≤ 2.5 ULN; If osseous metastasis or liver metastasis is developed and alkaline phosphatase is \> 2.5 ULN, than ALT and AST should be \< 1.5 ULN.
- Serum total bilirubin ≤ 1.5 ULN.
- PT: INR \< 1.7; PT \< (ULN + 4) s All test results should be within their normal ranges, and patients are not receiving continuous supportive treatment.
Exclusion
- 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.
- Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
- 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.).
Key Trial Info
Start Date :
December 29 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
December 12 2023
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT03302403
Start Date
December 29 2017
End Date
December 12 2023
Last Update
October 8 2020
Active Locations (1)
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1
First Affiliated Hospital of Wenzhou Medical University
Wenzhou, Zhejiang, China, 325000