RECRUITING

A Study with L19TNF in Combination with Lomustine in Patients with Glioblastoma At Progression or Recurrence

Conditions

Glioblastoma L19TNF Glioblastoma at progression

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The trial aims to collect safety, efficacy, exposure, dose- response, pharmacokinetic and pharmacodynamic information of the combination of L19TNF and lomustine at different dose levels in patients with Glioblastoma at progression or recurrence

Official Title

A Dose Optimization Study for L19TNF in Combination with Lomustine in Patients with Glioblastoma At Progression or Recurrence

Quick Facts

Study Start:2024-05-22

Study Completion:2026-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06336291

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Male or female, age ≥18. 2. Patients with histologically confirmed glioblastoma per 2021 WHO classification progression according to RANO criteria. 3. For operated patients, the histological report must document glioblastoma recurrence and a new MRI will need to be done at 3-5 weeks after surgery (directly before study treatment start). Study treatment will need to start minimum 4 weeks after surgery. 4. MGMT promotor status known. 5. Karnofsky Performance Status (KPS) ≥ 60%. 6. Documented negative test for HIV-HBV-HCV. For HBV serology, the determination of HbsAg and anti-HbcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required (HBV-DNA is not required for patients with documented vaccination report). For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible. 7. Female patients: female patients must be either documented not Women Of Childbearing Potential (WOCBP)\* or must have a negative pregnancy test within 14 days of starting treatment. 8. Male patients: male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and until 6 months after last study drug administration (e.g. condom with spermicidal gel). Double-barrier contraception is required. 9. 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 (WOCBP) 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).	1. Inability to undergo contrast-enhanced MRI. 2. Anti-cancer treatment with radiation therapy, chemotherapy, targeted therapies, immunotherapy, hormones, tumor treating fields or other antitumor therapies within 4 weeks prior to study treatment start. 3. Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start. 4. Grade ≥ 4 myelotoxicity with previous treatment of alkylating agents (e.g., TMZ, CCNU). 5. Previous treatment with Bevacizumab. 6. Previous treatment with L19TNF. 7. Previous treatment in the PH-L19TNFCCNU-02/20 study. 8. Known history of allergy to TNF, any excipient in the 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 hemoglobin (Hb) \< 9.0 g/dl. 10. Chronically impaired renal function as indicated by creatinine clearance \< 60 mL/min/1.73m2 or for patients older than 65 years without albuminuria or proteinuria, creatinine clearance \< 45 mL/min/1.73m2. 11. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN). 12. INR \> 1.5 ULN. 13. 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. 14. Active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent, in the judgement of the investigator. 15. History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris. 16. Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria). 17. Clinically significant cardiac arrhythmias or requiring permanent medication. 18. LVEF \<55% or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator. Patients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc \>470 milliseconds using Fredricia's QT correction formula) are excluded. 19. Uncontrolled hypertension. 20. Known arterial aneurism at high risk of rupture. 21. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification) 22. Anxiety ≥ CTCAE Grade 3. 23. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy. 24. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment. 25. Known active or latent tuberculosis (TB). 26. Pregnancy or breast feeding. 27. 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 ≤ 4 mg daily dexamethasone (or equivalent) for 7 days prior to start of treatment. Limited or occasional use of corticosteroids to treat or prevent acute adverse reactions is not considered an exclusion criterion. 28. 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. 29. Concurrent malignancies unless the patient has been disease-free without intervention for at least 2 years. 30. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment. 31. Serious, non-healing wound, ulcer, or bone fracture. 32. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months. 33. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin). 34. Requirement of concurrent use of other anti-cancer treatments or agents other than study medication. 35. Any recent live vaccination within 4 weeks prior to treatment or plan to receive live vaccination during the study.

Inclusion Criteria

Exclusion Criteria

1. Male or female, age ≥18.
2. Patients with histologically confirmed glioblastoma per 2021 WHO classification progression according to RANO criteria.
3. For operated patients, the histological report must document glioblastoma recurrence and a new MRI will need to be done at 3-5 weeks after surgery (directly before study treatment start). Study treatment will need to start minimum 4 weeks after surgery.
4. MGMT promotor status known.
5. Karnofsky Performance Status (KPS) ≥ 60%.
6. Documented negative test for HIV-HBV-HCV. For HBV serology, the determination of HbsAg and anti-HbcAg Ab is required. In patients with serology documenting previous exposure to HBV, negative serum HBV-DNA is required (HBV-DNA is not required for patients with documented vaccination report). For HCV, HCV-RNA or HCV antibody test is required. Subjects with a positive test for HCV antibody but no detection of HCV-RNA indicating no current infection are eligible.
7. Female patients: female patients must be either documented not Women Of Childbearing Potential (WOCBP)\* or must have a negative pregnancy test within 14 days of starting treatment.
8. Male patients: male subjects able to father children must agree to use two acceptable methods of contraception throughout the study and until 6 months after last study drug administration (e.g. condom with spermicidal gel). Double-barrier contraception is required.
9. 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 (WOCBP) 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).

1. Inability to undergo contrast-enhanced MRI.
2. Anti-cancer treatment with radiation therapy, chemotherapy, targeted therapies, immunotherapy, hormones, tumor treating fields or other antitumor therapies within 4 weeks prior to study treatment start.
3. Subjects who participated in an investigational drug or device study within 4 weeks prior to study treatment start.
4. Grade ≥ 4 myelotoxicity with previous treatment of alkylating agents (e.g., TMZ, CCNU).
5. Previous treatment with Bevacizumab.
6. Previous treatment with L19TNF.
7. Previous treatment in the PH-L19TNFCCNU-02/20 study.
8. Known history of allergy to TNF, any excipient in the 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 hemoglobin (Hb) \< 9.0 g/dl.
10. Chronically impaired renal function as indicated by creatinine clearance \< 60 mL/min/1.73m2 or for patients older than 65 years without albuminuria or proteinuria, creatinine clearance \< 45 mL/min/1.73m2.
11. Inadequate liver function (ALT, AST, ALP ≥ 2.5 x ULN or total bilirubin ≥ 1.5 x ULN).
12. INR \> 1.5 ULN.
13. 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.
14. Active or history of autoimmune disease that might deteriorate when receiving an immune-stimulatory agent, in the judgement of the investigator.
15. History within the last year of cerebrovascular disease and/or acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
16. Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
17. Clinically significant cardiac arrhythmias or requiring permanent medication.
18. LVEF \<55% or any other abnormalities observed during baseline ECG and echocardiogram investigations that are considered as clinically significant by the investigator. Patients with a marked prolongation of QT/QTc interval (e.g., repeated demonstration of QTc \>470 milliseconds using Fredricia's QT correction formula) are excluded.
19. Uncontrolled hypertension.
20. Known arterial aneurism at high risk of rupture.
21. Ischemic peripheral vascular disease (Grade IIb-IV according to Leriche-Fontaine classification)
22. Anxiety ≥ CTCAE Grade 3.
23. Severe diabetic retinopathy such as severe non-proliferative retinopathy and proliferative retinopathy.
24. Major trauma including major surgery (such as abdominal/cardiac/thoracic surgery) within 3 weeks of administration of study treatment.
25. Known active or latent tuberculosis (TB).
26. Pregnancy or breast feeding.
27. 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 ≤ 4 mg daily dexamethasone (or equivalent) for 7 days prior to start of treatment. Limited or occasional use of corticosteroids to treat or prevent acute adverse reactions is not considered an exclusion criterion.
28. 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.
29. Concurrent malignancies unless the patient has been disease-free without intervention for at least 2 years.
30. Growth factors or immunomodulatory agents within 7 days prior to the administration of study treatment.
31. Serious, non-healing wound, ulcer, or bone fracture.
32. Deep vein thrombosis, pulmonary embolism or other acute vascular events within 6 months.
33. Anticoagulation therapy with P2Y12 antagonists (e.g., clopidogrel, ticagrelor) and vitamin K antagonists (e.g., phenprocoumon, warfarin).
34. Requirement of concurrent use of other anti-cancer treatments or agents other than study medication.
35. Any recent live vaccination within 4 weeks prior to treatment or plan to receive live vaccination during the study.

Contacts and Locations

Study Contact

Teresa Hemmerle, PhD

CONTACT

+390577017816

regulatory@philogen.com

Marco Taras

CONTACT

+390577017816

regulatory@philogen.com

Study Locations (Sites)

Northwestern Memorial Hospital

Chicago, Illinois, 60611

United States

Massachusetts General Hospital (MGH)

Boston, Massachusetts, 02114

United States

Beth Israel Deaconess Medical Center (BIDMC)

Boston, Massachusetts, 02215

United States

Dana-Farber Cancer Institute (DFCI)

Boston, Massachusetts, 02215

United States

Memorial Sloan Kettering Cancer Center

New York, New York, 10065

United States

Abramson Cancer Center of the University of Pennsylvania

Philadelphia, Pennsylvania, 19104

United States

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232

United States

University of Virginia (UVA)

Charlottesville, Virginia, 22903

United States

Collaborators and Investigators

Sponsor: Philogen S.p.A.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-05-22

Study Completion Date2026-06

Study Record Updates

Study Start Date2024-05-22

Study Completion Date2026-06

Terms related to this study

Keywords Provided by Researchers

L19TNF
Glioblastoma at progression

Additional Relevant MeSH Terms

Glioblastoma