PD-1 Antibody Expressing CAR T Cells for Mesothelin Positive Advanced Malignancies

NCT03030001 | Unknown Phase 1 DMC

• 1 other identifier: H2017-01-P01
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, one center, dose escalation clinical study, to determine the safety and efficacy of infusion of autologous T cells engineered to express immune checkpoint antibody and chimeric antigen receptor targeting mesothelin in adult patients with mesothelin positive, recurrent or refractory malignant tumors.

Conditions

Solid Tumor, Adult; Advanced Cancer

Keywords

mesothelin; PD-1; CAR T; solid tumor

Outcome Measures

Primary Outcomes (1)

• Safety of infusion of autologous mesothelin specific CAR T cells

  Safety of infusion of autologous mesothelin specific CAR T cells with PD-1 antibody expressing in patients with relapsed or refractory advanced solid malignancies using the NCI CTCAE V4.0 criteria

  2 years

Secondary Outcomes (3)

• the response evaluation criteria of solid tumor

  2 years

• progression free survival

  1 year

• overall survival

  2 years

Other Outcomes (3)

• Change of life quality after treatment

  2 years

• proliferation and persistence of mesothelin specific CAR T cells in patients after treatment

  6 months

• expression of PD-1 antibody in patients after treatment

  6 months

Study Arms (1)

PD-1 antibody expressing CAR-T cells

EXPERIMENTAL

PD-1 antibody expressing mesothelin specific CAR-T cells

Biological: PD-1 antibody expressing mesothelin specific CAR-T cells

Interventions

PD-1 antibody expressing mesothelin specific CAR-T cells BIOLOGICAL

Patients will receive an IV infusion of PD-1 antibody expressing mesothelin specific CAR engineered peripheral blood leukocyte. On day 21, cells will be infused intravenously (i.v.) on the Patient Care Unit over 20 to 30 minutes.

PD-1 antibody expressing CAR-T cells

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. Relapsed or refractory advanced solid malignancies.
• \. Progressive disease and no response to current therapy.
• \. Patients must have previously received at least one standard therapy for their cancer (if available) and have been either non-responders (progressive disease) or have recurred. And patients are willing to attend the clinical trial.
• \. Gender unlimited, age from 18 years to 80 years.
• \. Life expectancy≥6 months.
• \. ECOG (Eastern Cooperative Oncology Group) performance status of 0-2.
• \. Adequate venous access for apheresis, and no other contraindications for leukapheresis ; Peripheral venous access ；no contraindication of lymphocyte separation.
• \. IHC( immuno-histochemistry) result of tumor tissue： mesothelin positive for ：frequency≥2，intensity≥2 +. The percentage of tumor cell nuclei stained (0, no staining; 1, ≤10%; 2, 10-50% and 3, \>50%) and the staining intensity (ranging from 0 to 3+).
• \. Adequate hepatic function, renal function and bone marrow function：WBC≥3.0×109/L,PLT≥60×109/L,HGB≥85g/L,LY≥0.7×109/L; Alanine aminotransferase/Aspartate transaminase(ALT/AST) 2.5 times the upper limit of the normal value, total bilirubin(TBiL) 1times the upper limit of the normal value, Serum creatinine1.5 times the upper limit of the normal value.
• \. Willing and able to understand and sign the Informed Consent Document.
• \. Women of child-bearing age must have evidence of negative pregnancy test. Patients must be willing to practice birth control during and for four months following treatment.

You may not qualify if:

• \. Life expectancy6 months.
• \. Patients with uncontrolled active infection will be excluded.
• \. Patients with severe heart and lung dysfunction; uncontrolled hypertension, 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; aberrant pulmonary function testing: with a forced expiratory volume (FEV) of \<30%(predicted), diffusion capacity of the lung for carbon monoxide (DLCO) (corrected) \<30% and oxyhemoglobin saturation90% will be excluded.
• \. Patients with severe liver and kidney dysfunction or chronic diseases of important organs will be excluded.
• \. Patients with active autoimmune disease requiring immunosuppressive therapy will be excluded.
• \. Patients requiring corticosteroids (other than inhaled) will be excluded.
• \. Patients with other severe diseases or situations improper for the research will be excluded, including neurologic disease, mental disease, immune disease, metabolic disease, and contagious disease.
• \. Pregnant and/or lactating women will be excluded.
• \. Patients who have had other bio-therapy in the past 4 weeks.
• \. Patients who are participating or participated any other clinical trials in latest 30 days will be excluded.
• \. Patients with the subject suffering disease affects the understanding of informed consent or complying with study protocol will be excluded.

Sponsors & Collaborators

• Ningbo Cancer Hospital: lead

Study Sites (1)

Ningbo No.5 Hospital (Ningbo Cancer Hospital)

Ningbo, Zhejiang, China

RECRUITING

Study Officials

• Qijun Qian, PhD

  Shanghai Cell Therapy Engineering Research Institute

  STUDY CHAIR

Central Study Contacts

Huajun Jin, PhD

CONTACT

86-13162257545; hj_jin@126.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 20, 2017
• First Posted: January 24, 2017
• Study Start: February 15, 2017
• Primary Completion: December 1, 2018
• Study Completion: February 1, 2019
• Last Updated: January 24, 2017

Record last verified: 2017-01

Locations

CN (1)