CAR-T Cell Immunotherapy in MUC1 Positive Solid Tumor

• ClinicalTrials.gov Identifier: NCT02617134
• Recruitment Status: Unknown
• First Posted: November 30, 2015
• Last Update Posted: December 6, 2016
• Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Collaborators: The First People's Hospital of Hefei; Hefei Binhu Hospital
• Information provided by (Responsible Party): PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Tracking Information

• First Submitted Date: November 26, 2015
• First Posted Date: November 30, 2015
• Last Update Posted Date: December 6, 2016
• Study Start Date: November 2015
• Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 26, 2015)

Adverse events attributed to the administration of the anti-MUC1 CAR-T cells [ Time Frame: 2 years ]

Determine the toxicity profile of the MUC1 targeted CAR-T cells with Common Toxicity Criteria for Adverse Effects (CTCAE) version 4.0.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 26, 2015)

Objective Response Rate [ Time Frame: Safety follow-up is 100 days from last CAR-T infusion. ]

The objective response rate (ORR) is defined as the proportion of patients who achieve radiographic partial or complete response (PR or CR) according to the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 guideline.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: CAR-T Cell Immunotherapy in MUC1 Positive Solid Tumor
• Official Title: Immunotherapy With Chimeric Antigen Receptor-Modified T Cells for MUC1 Positive Advanced Refractory Solid Tumor
• Brief Summary: The purpose of this study is to evaluate the safety and effectiveness of CAR-T cell immunotherapy in patients with MUC1 positive relapsed or refractory solid tumor.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Malignant Glioma of Brain
• Colorectal Carcinoma
• Gastric Carcinoma

Intervention

Biological: anti-MUC1 CAR-T cells

Other Name: anti-MUC1-CAR transduced autologous T cells

Study Arms

Experimental: CAR-T cell immunotherapy

Enrolled patients will receive CAR-T cell immunotherapy with a novel specific chimeric antigen receptor targeting MUC1 antigen by infusion.

Intervention: Biological: anti-MUC1 CAR-T cells

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: November 26, 2015): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: November 2018
• Estimated Primary Completion Date: November 2017 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

Male and female subjects with MUC1+ malignancies in patients with no available curative treatment options who have limited prognosis (several months to < 2 year survival) with currently available therapies will be enrolled:

• Eligible diseases: MUC1+ malignant glioma of brain, colorectal carcinoma and gastric carcinoma.

  1a. Malignant Glioma of Brain Failure after previous standard of care initial treatment of glioblastoma multiforme; documentation by magnetic resonance imaging (MRI) of an interval increase in nodular gadolinium enhancement consistent with recurrent malignant glioma suitable for therapeutic re-resection; previous pathological diagnosis of World Health Organization (WHO) Grade IV glioma;

  1b. Colorectal Carcinoma Patients must have histologically proven adenocarcinoma primary to the colon or rectum and clinical or pathologic evidence of distant metastasis;

  1c. Gastric Carcinoma Histologically confirmed adenocarcinoma of the stomach, gastroesophageal junction or esophagus; metastatic disease or locally advanced disease not amenable to curative surgery.

• Patients 18 years of age or older, and must have a life expectancy > 12 weeks.
• MUC1 is expressed in malignancy tissues by immuno-histochemical (IHC).
• Eastern cooperative oncology group (ECOG) performance status of 0-2 or karnofsky performance status (KPS) score is higher than 60.
• Adequate venous access for apheresis or venous sampling, and no other contraindications for leukapheresis.
• Females of child-bearing potential must have a negative pregnancy test and all subjects must agree to use an effective method of contraception for up to two weeks after the last infusion of CAR T cells.
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements: White blood cell count (WBC) ≥ 2500c/ml, Platelets ≥ 50×10^9/L, Hb ≥ 9.0g/dL, lymphocyte (LY) ≥ 0.7×10^9/L, LY% ≥ 15%, Alb ≥ 2.8g/dL, serum lipase and amylase < 1.5×upper limit of normal, serum creatinine ≤ 2.5mg/dL, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 5×upper limit of normal, serum total bilirubin ≤ 2.0mg/dL. These tests must be conducted within 7 days prior to registration.
• Ability to give informed consent.

Exclusion Criteria:

• The transduction efficiency of the T cells is less than 30% or the amplification of the T cells via artificial antigen presenting cell (aAPC) stimulation is less than 5 times.
• Pregnant or nursing women may not participate.
• Known HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• Serious illness or medical condition which would not permit the patient to be managed according to the protocol, including active uncontrolled infection, major cardiovascular, coagulation disorders, respiratory or immune system, myocardial infarction, cardiac arrhythmias, obstructive/restrictive pulmonary disease, or psychiatric or emotional disorders.
• History of severe immediate hypersensitivity to any of the agents including cyclophosphamide, fludarabine, or aldesleukin.
• Concurrent use of systemic steroids. Recent or current use of inhaled steroids is not exclusionary.
• Previously treatment with any gene therapy products.
• The existence of unstable or active ulcers or gastrointestinal bleeding.
• Patients with portal vein vascular invasion or extrahepatic, are excluded from this study.
• Patients with a history of organ transplantation or are waiting for organ transplantation.
• Patients need anticoagulant therapy (such as warfarin or heparin).
• Patients need long-term antiplatelet therapy (aspirin at a dose > 300mg/d; clopidogrel at a dose > 75mg/d).
• Patients treated by radiotherapy within 4 weeks prior the first apheresis.
• Patients using fludarabine or cladribine chemotherapy within two years.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02617134
• Other Study ID Numbers: PG-021-002
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Study Sponsor: PersonGen BioTherapeutics (Suzhou) Co., Ltd.

Collaborators

• The First People's Hospital of Hefei
• Hefei Binhu Hospital

Investigators

• Principal Investigator: Lin Yang, Ph.D.; PersonGen BioTherapeutics (Suzhou) Co., Ltd.

• PRS Account: PersonGen BioTherapeutics (Suzhou) Co., Ltd.
• Verification Date: July 2016