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Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133

Primary Purpose

Liver Cancer, Pancreatic Cancer, Brain Tumor

Status
Completed
Phase
Phase 1
Locations
China
Study Type
Interventional
Intervention
anti-CD133-CAR vector-transduced T cells
Sponsored by
Chinese PLA General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Liver Cancer

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Chemotherapy refractory or relapsed CD133-positive liver cancer, pancreatic cancer, brain tumor ,breast cancer, ovarian tumors, colorectal cancer and acute leukemia.
  2. Patients must be 18 years of age or older.
  3. Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2.

  4. Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters:

    Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter).

    Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m.

  5. Seronegative for HIV antibody.
  6. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody.
  7. Patients must be willing to practice birth control during and for four months following treatment. NOTE: women of child-bearing age must have evidence of negative pregnancy test.
  8. Patients must be willing to sign an informed consent.

Exclusion Criteria:

  • 1. Patients with life expectancy less than 12 months will be excluded. 2. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded.

    3. Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air.

    4. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded.

    5. Pregnant and/or lactating women will be excluded. 6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors.

    7. Patients with any type of primary immunodeficiencies will be excluded from the study.

    8. Patients requiring corticosteroids (other than inhaled) will be excluded. 9. Patients with history of T cell tumors will be excluded. 10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.

    11. Patients with relapsed acute leukemia after allogeneic stem cell transplantation

Sites / Locations

  • Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

anti-CD133 CAR T cells

Arm Description

Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Patients receive anti-CD133-CAR retroviral vector-transduced autologous-derived T cells on days 0, 1, 2 in the absence of disease progression or unacceptable toxicity.

Outcomes

Primary Outcome Measures

Occurrence of study related adverse events
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical

Secondary Outcome Measures

Anti-tumor responses to CART-133 cell infusions

Full Information

First Posted
September 2, 2015
Last Updated
December 15, 2019
Sponsor
Chinese PLA General Hospital
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1. Study Identification

Unique Protocol Identification Number
NCT02541370
Brief Title
Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133
Official Title
Clinical Study of Chimeric CD(Cluster of Differentiation)133 Antigen Receptor-modified T Cells in Relapsed and/or Chemotherapy Refractory Malignancies
Study Type
Interventional

2. Study Status

Record Verification Date
June 2015
Overall Recruitment Status
Completed
Study Start Date
June 2015 (undefined)
Primary Completion Date
June 2019 (Actual)
Study Completion Date
June 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Chinese PLA General Hospital

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RATIONALE: Placing a tumor antigen chimeric receptor that has been created in the laboratory into patient autologous or donor-derived T cells may make the body build immune response to kill cancer cells. PURPOSE: This clinical trial is studying genetically engineered lymphocyte therapy in treating patients with Relapsed and/or Chemotherapy Refractory Advanced Malignancies.
Detailed Description
I. Determine the safety and feasibility of the chimeric antigen receptor T cells transduced with the anti-CD133 (cluster of differentiation antigen 133 ) vector (referred to as CART-133 cells). II. Determine duration of in vivo survival of CART-133 cells. RT-PCR (reverse transcription polymerase chain reaction) analysis of whole blood will be used to detect and quantify survival of CART-133 TCR (T-cell receptor) zeta:CD137 and TCR zeta cells over time. SECONDARY OBJECTIVES: I. For patients with detectable disease, measure anti-tumor response due to CART-133 cell infusions. II. To determine if the CD137 transgene is superior to the TCR zeta only transgene as measured by the relative engraftment levels of CART-133 TCR zeta:CD137 and TCR zeta cells over time. III. Estimate relative trafficking of CART-133 cells to tumor in bone marrow and lymph nodes. IV. For patients with stored or accessible tumor cells determine tumor cell killing by CART-133 cells in vitro. V. Determine if cellular or humoral host immunity develops against the murine anti-CD133, and assess correlation with loss of detectable CART-133 (loss of engraftment). VI. Determine the relative subsets of CART-133 T cells (Tcm, Tem, and Treg).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Liver Cancer, Pancreatic Cancer, Brain Tumor, Breast Cancer, Ovarian Tumor, Colorectal Cancer, Acute Myeloid and Lymphoid Leukemias

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
anti-CD133 CAR T cells
Arm Type
Experimental
Arm Description
Dose escalation will occur using a standard 3+3 dose escalation approach, beginning in dose level I with dose cohorts and rules for escalation and de-escalation. Patients receive anti-CD133-CAR retroviral vector-transduced autologous-derived T cells on days 0, 1, 2 in the absence of disease progression or unacceptable toxicity.
Intervention Type
Biological
Intervention Name(s)
anti-CD133-CAR vector-transduced T cells
Other Intervention Name(s)
genetically engineered lymphocyte therapy
Intervention Description
genetically engineered lymphocyte therapy
Primary Outcome Measure Information:
Title
Occurrence of study related adverse events
Description
defined as >= Grade 3 signs/symptoms, laboratory toxicities, and clinical
Time Frame
Until week 24
Secondary Outcome Measure Information:
Title
Anti-tumor responses to CART-133 cell infusions
Time Frame
up to 24 weeks
Other Pre-specified Outcome Measures:
Title
in vivo existence of CART133
Time Frame
1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Chemotherapy refractory or relapsed CD133-positive liver cancer, pancreatic cancer, brain tumor ,breast cancer, ovarian tumors, colorectal cancer and acute leukemia. Patients must be 18 years of age or older. Patients must have an ECOG (Eastern Cooperative Oncology Group )performance status of 0-2. Patients must have evidence of adequate bone marrow reserve, hepatic and renal function as evidenced by the following laboratory parameters: Absolute neutrophil count greater than 1500/mm3. Platelet count greater than 100,000/mm3. Hemoglobin greater than 10g/dl (patients may receive transfusions to meet this parameter). Total bilirubin < 1.5 times upper limits of normal. Serum creatinine less than or equal to 1.6 mg/ml or the creatinine clearance must be greater than 70 ml/min/1.73m. Seronegative for HIV antibody. Seronegative for active hepatitis B, and seronegative for hepatitis C antibody. Patients must be willing to practice birth control during and for four months following treatment. NOTE: women of child-bearing age must have evidence of negative pregnancy test. Patients must be willing to sign an informed consent. Exclusion Criteria: 1. Patients with life expectancy less than 12 months will be excluded. 2. Patients with uncontrolled hypertension (> 160/95), unstable coronary disease evidenced by uncontrolled arrhythmias, unstable angina, decompensated congestive heart failure (> New York Heart Association Class II), or myocardial infarction within 6 months of study will be excluded. 3. Patients with any of the following pulmonary function abnormalities will be excluded: FEV(forced expiratory volume), < 30% predicted; DLCO (diffusing capacity of lung for carbon monoxide) < 30% predicted (post-bronchodilator); Oxygen Saturation less than 90% on room air. 4. Patients with severe liver and kidney dysfunction or consciousness disorders will be excluded. 5. Pregnant and/or lactating women will be excluded. 6. Patients with active infections, including HIV, will be excluded, due to unknown effects of the vaccine on lymphoid precursors. 7. Patients with any type of primary immunodeficiencies will be excluded from the study. 8. Patients requiring corticosteroids (other than inhaled) will be excluded. 9. Patients with history of T cell tumors will be excluded. 10. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded. 11. Patients with relapsed acute leukemia after allogeneic stem cell transplantation
Facility Information:
Facility Name
Biotherapeutic Department and Pediatrics Department of Chinese PLA General Hospital
City
Beijing
State/Province
Beijing
ZIP/Postal Code
100853
Country
China

12. IPD Sharing Statement

Citations:
PubMed Identifier
33312759
Citation
Dai H, Tong C, Shi D, Chen M, Guo Y, Chen D, Han X, Wang H, Wang Y, Shen P. Efficacy and biomarker analysis of CD133-directed CAR T cells in advanced hepatocellular carcinoma: a single-arm, open-label, phase II trial. Oncoimmunology. 2020 Nov 25;9(1):1846926. doi: 10.1080/2162402X.2020.1846926.
Results Reference
derived
PubMed Identifier
28057014
Citation
Feng KC, Guo YL, Liu Y, Dai HR, Wang Y, Lv HY, Huang JH, Yang QM, Han WD. Cocktail treatment with EGFR-specific and CD133-specific chimeric antigen receptor-modified T cells in a patient with advanced cholangiocarcinoma. J Hematol Oncol. 2017 Jan 5;10(1):4. doi: 10.1186/s13045-016-0378-7.
Results Reference
derived

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Treatment of Relapsed and/or Chemotherapy Refractory Advanced Malignancies by CART133

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