Overview

A Study Evaluating Temferon in Patients With Glioblastoma & Unmethylated MGMT

Status:
Recruiting
Trial end date:
2022-12-01
Target enrollment:
0
Participant gender:
All
Summary
This is a non-randomized, open label, phase I/IIa, dose-escalation study, involving a single injection of Temferon, an investigational advanced therapy consisting of autologous CD34+-enriched hematopoietic stem and progenitor cells exposed to transduction with a lentiviral vector driving myeloid specific interferon-alpha2 expression, which will be administered to up to 21 patients affected by GBM who have an unmethylated MGMT promoter. Part A will evaluate the safety and tolerability of 3 escalating doses of Temferon and 2 different conditioning regimens in up to 15 patients, following first line treatment. In Part B, a further 6 patients will receive a single dose of Temferon, as identiifed from Part A.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Genenta Science
Treatments:
Interferons
Criteria
Inclusion Criteria:

- 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:

- 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;

- 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);

- Serum creatinine < 2x upper limit normal and estimated glomerular filtration rate
(eGFR) ≥ 30ml/min/1.73m^2;

- 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.

- Hemoglobin ≥10 g/dL, platelet count ≥100000/mm^3, absolute neutrophil count
>1500/mm^3.

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), busulfan, 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, immunemediated 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.