A clinical gene therapy study with hematopoietic stem cells for the treatment of patients suffering from a malignant neoplasm of the central nervous system

Phase 1

• Conditions: Glioblastoma Multiforme; MedDRA version: 20.0 Level: PT Classification code 10018337 Term: Glioblastoma multiforme System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 20.0 Level: PT Classification code 10018336 Term: Glioblastoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2018-001404-11-IT
• Lead Sponsor: GENENTA SCIENCE SR

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-06-12
• Last Update Posted: 30 June 2019

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Not specified
• Target Recruitment: 21

Inclusion Criteria

Inclusion Criteria at Screening:
• Patients aged between 18 and =70.
• Histologically confirmed, newly diagnosed supratentorial
glioblastoma with unmethylated MGMT gene promoter.
• Patients have undergone complete or partial tumor resection.
• Able and willing to provide written informed consent and comply with the study protocol and procedures. • Eligible for radiotherapy.
• Life expectancy of 6 months or more at Screening.
• Women of child-bearing potential enrolled in the study must
have a negative pregnancy test at screening and agree to use
acceptable methods of contraception during the trial.
• Men enrolled in the study with partners who are women of
child-bearing potential, must be willing to use an acceptable
barrier contraceptive method during the trial or have undergone
successful vasectomy at least 6 months prior to entry into the
study. Successful vasectomy needs to have been confirmed by
semen analysis.
• Karnofsky performance score (KPS)=70.
Additional inclusion criteria to be assessed within 20 days of Temferon administration:
• Adequate cardiac, renal, hepatic and pulmonary function as evidenced by:
o Left ventricular ejection fraction (LVEF) = 45% by echo and normal electrocardiogram (ECG) or presence of abnormalities not significant for cardiac disease.
Absence of severe pulmonary hypertension;
o Diffusing capacity of the lung for carbon monoxide (DLCO) >50% and forced expiratory volume in 1 sec (FEV1) and forced expiratory vital capacity (FVC) >60% predicted (if non cooperative: pulse oximetry > 95% in room air);
o Serum creatinine < 2x upper limit normal and estimated
glomerular filtration rate (eGFR) = 30ml/min/1.73m^2;
o Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) = 2.5 x upper limit of normal (ULN), and total bilirubin = 2.0 mg/dl.
o Hemoglobin =10 g/dL, platelet count =100000/mm^3,
absolute neutrophil count >1500/mm^3.
Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 17
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 4

Exclusion Criteria

•Use of other investigational agents or procedures within 4 weeks prior to study enrolment (within 6 weeks if use of long-acting agents) or participation in a previous gene therapy study.
•Known hypersensitivity to carmustine (or any other nitrosurea), thiotepa, lenograstim, plerixafor, or any excipients used in these products.
•Receipt of any oral or parenteral chemotherapy or immunotherapy within 2 years of Screening. •Previous allogeneic bone marrow transplantation, kidney or liver transplant.
•Clinical evidence of persistent raised intracranial pressure following surgical resection. •Clinically relevant active viral, bacterial, or fungal infection at eligibility evaluation.
•Active autoimmune disease or a relevant history of important autoimmune manifestations, in particular psoriasis, systemic lupus erythematosus (SLE), rheumatoid arthritis, vasculitis, immune-mediated peripheral neuropathies.
•History of sarcoidosis.
•History or current evidence of neuropsychiatric illness including depression, schizophrenia, bipolar disorders, impaired cognitive function, dementia or suicidal tendency.
•History of severe cardiovascular disease such as prior stroke, coronary artery disease requiring intervention or unresolved arrhythmias in the past 6 months.
•Evidence of any hematological neoplasm.
•Positivity for human immunodeficiency virus type 1 or 2 (HIV-1, HIV-2) (serology or RNA), and/or Hepatitis B Virus Surface Antigen (HbsAg) and/or Hepatitis B Virus (HBV) DNA and/or Hepatitis C virus (HCV) RNA (or negative HCV RNA but on antiviral treatment) and/or Treponema Pallidum or Mycoplasma active infection.
•Active alcohol or substance abuse within 6 months of the study.
•Current pregnancy or lactation.
•Known bleeding diathesis or history of abnormal bleeding, or any other known coagulation abnormalities that would contraindicate lumbar puncture for CSF or future surgery.
•Use of immunosuppressants with the exception of steroids. The maximum permitted dexamethasone (or equivalent) dose is 4 mg per day.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified