Overview

Safety and Efficacy of L19TNF in Patients With Isocitrate Dehydrogenase (IDH) Wildtype WHO Grade III / IV Glioma at First Relapse

Status:
Recruiting
Trial end date:
2021-12-01
Target enrollment:
0
Participant gender:
All
Summary
Open label, non-randomized, mono-center Phase I/II study in subjects with IDH-wildtype WHO grade III / IV glioma at first relapse.
Phase:
Phase 1/Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Philogen S.p.A.
Criteria
Inclusion Criteria:

1. Male or female, age 18 or more

2. Patients with histologically confirmed IDH-wildtype WHO grade III / IV glioma at first
relapse

3. Radiographic demonstration of disease progression

4. Presence of at least one lesion of bi-dimensionally measurable disease by MRI of at
least 1 cm (10 mm) in the longest diameter on baseline MRI.

5. Karnofsky Performance Score (KPS) ≥ 70%

6. Documented negative test for HIV-HBV-HCV. For HBV serology: the determination of
HBsAg, anti-HBsAg-Ab and anti-HBcAg-Ab is required. In patients with serology
documenting previous exposure to HBV (i.e., anti-HBs Ab with no history of vaccination
and/or anti-HBc Ab), negative serum HBV-DNA is required. For HCV: HCV-RNA or HCV
antibody test. Subjects with a positive test for HCV antibody but no detection of
HCV-RNA indicating no current infection are eligible.

7. Female patients: negative pregnancy test for women of childbearing potential (WOCBP)*
within 14 days of starting treatment. WOCBP must agree to use, from the screening to
six months following the last study drug administration, highly effective
contraception methods, as defined by the "Recommendations for contraception and
pregnancy testing in clinical trials" issued by the Head of Medicine Agencies'
Clinical Trial Facilitation Group (www.hma.eu/ctfg.html) and which include, for
instance, progesteron-only or combined (estrogen- and progesteron-containing) hormonal
contraception associated with inhibition of ovulation, intrauterine devices,
intrauterine hormone-releasing systems, bilateral tubal occlusion or vasectomized
partner.

Male patients: Male subjects able to father children must agree to use two acceptable
methods of contraception throughout the study (e.g. condom with spermicidal gel).
Double-barrier contraception is required.

8. Negative TB test (e.g. Mantoux or Quantiferon assay).

9. Evidence of a personally signed and dated informed consent document indicating that
the subject has been informed of all pertinent aspects of the study.

10. Willingness and ability to comply with the scheduled visits, treatment plan,
laboratory tests and other study procedures *Women of childbearing potential are
defined as females who have experienced menarche, are not postmenopausal (12 months
with no menses without an alternative medical cause) and are not permanently
sterilized (e.g., tubal occlusion, hysterectomy, bilateral oophorectomy or bilateral
salpingectomy)

Exclusion Criteria:

1. Second or later glioma progression.

2. Surgical resection or biopsy of glioma within 4 weeks of the start of study treatment.

3. Subjects who participated in an investigational drug or device study within 4 weeks
prior to study treatment start.

4. Treatment with tumor-treating fields

5. Radiotherapy within 6 weeks prior to study treatment start.

6. Patients unable to undergo contrast-enhanced MRI.

7. Patient taking herbal medications within 7 days prior to first dose of the study drug.

8. Known history of allergy to TNF, excipient in study medication or any other
intravenously administered human proteins/peptides/antibodies.

9. Absolute neutrophil count (ANC) < 1.5 x 10^9/L, platelets < 100 x 10^9/L or
haemoglobin (Hb) < 9.0 g/dl.

10. Chronically impaired renal function as indicated by creatinine clearance < 60 mL/min.

11. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 2.0 x ULN)

12. Any severe concomitant condition which makes it undesirable for the patient to
participate in the study or which could jeopardize compliance with the protocol, in
the opinion of the investigator.

13. History within the last year of cerebrovascular disease and/or acute or subacute
coronary syndromes including myocardial infarction, unstable or severe stable angina
pectoris.

14. Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).

15. Clinically significant cardiac arrhythmias or requiring permanent medication.

16. Abnormal LVEF or any other abnormalities observed during baseline ECG and
echocardiogram investigations that are considered as clinically significant by the
investigator.

17. Uncontrolled hypertension.

18. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine
classification).

19. Medically documented history of or active major depressive episode, bipolar disorder
(I or II), obsessive-compulsive disorder, schizophrenia, a history of suicidal attempt
or ideation, or homicidal ideation (e.g. risk of doing harm to self or others), or
patients with active severe personality disorders.

20. Anxiety ≥ CTCAE grade 3

21. Severe diabetic retinopathy such as severe non-proliferative retinopathy and
proliferative retinopathy.

22. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery)
within 4 weeks of administration of study treatment.

23. Pregnancy or breast-feeding.

24. Requirement of chronic administration of high dose corticosteroids or other
immunosuppressant drugs. Subjects must have been either off corticosteroids, or on a
stable or decreasing dose ≤ 10 mg daily prednisone (or equivalent) for at least 2
weeks prior to study treatment start. Limited or occasional use of corticosteroids to
treat or prevent acute adverse reactions is not considered an exclusion criterion.

25. Presence of active and uncontrolled infections or other severe concurrent disease,
which, in the opinion of the investigator, would place the patient at undue risk or
interfere with the study.

26. Concurrent malignancies, unless the patient has been disease-free for at least 2
years.

27. Growth factors or immunomodulatory agents within 7 days prior to the administration of
study treatment.

28. Serious, non-healing wound, ulcer or bone fracture.

29. Requirement of concurrent therapy with anticoagulants at therapeutic doses.

30. Requirement of concurrent use of other anti-cancer treatments or agents other than
study medication.

31. Any recent live vaccination within 4 weeks prior to treatment or plan to receive
vaccination during the study.