IDH1-vac in Patients With Newly Diagnosed IDH1R132H-positive High-grade Astrocytomas

Korábbi kezelés

• Previous or concurrent experimental treatment for the tumor. This includes local therapies such as interstitial radiotherapy or local chemotherapy (i.e., BCNU wafers), loco-regional hyperthermia, and antiangiogenic therapy (such as bevacizumab)
• Antitumor treatment other than standard radiotherapy and/or standard TMZ chemotherapy. Daily metronomic TMZ or intensified dosing scheduled as a substitute for maintenance TMZ cycles are not allowed. (Dose reductions of standard TMZ chemotherapy are allowed.)
• Patients with severe infection(s) or signs/symptoms of infection within 2 weeks prior to the first administration of the study drug
• Patients who have received a live, attenuated vaccine within 4 weeks prior to the first administration of the study drug
• Patients with a prior solid organ transplantation or haematopoietic stem cell transplantation
• Participation in other interventional clinical trials or their observation period during the last 30 days before the first administration of the IMP.

Más betegség

• Progressive (incl. pseudoprogression) or recurrent disease within 3 to 6 weeks after SOC radiation therapy based on local MRI assessment
• Patients with history or presence of HIV and/or HBV/HCV positivity (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive
• History of hypersensitivity to the IMP or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the IMP

Laborértékek

• Abnormal laboratory values for hematology, liver and renal function (serum creatinine). In detail the following values apply as exclusion criteria:
  • Hemoglobin < 10 g/dL (6.2 mmol/L)
  • White blood cell count (WBC) decrease (<3.0 x 109/L) or increase (>10.0 x 109/L)
  • Absolute neutrophil count (ANC) decrease (< 1.5 x 109/L)
  • Platelet count decrease (< 75 x 109/L)
  • Bilirubin > 1.5 x ULN (upper limit of normal according to the performing lab's reference range)
  • ALT > 3 x ULN
  • AST > 3 x ULN
  • GGT > 2.5 x ULN
  • Serum creatinine increase (> 1.5 x ULN)

Egyéb

• Pregnancy and lactation

• Patients present with newly diagnosed histologically confirmed WHO grade 3 to 4 astrocytoma, IDH1R132H-positive (with or without measurable residual tumor after tumor resection or biopsy)
• Absence of chromosomal 1p/19q co-deletion in the tumor tissue
• Loss of nuclear ATRX expression in the tumor tissue (partial loss allowed)
• Availability of tumor tissue for molecular analysis (FFPE bulk tissue or cryo tissue) is required
• Patients have received radiotherapy (54 - 60 Gy) alone or combined with TMZ and radiotherapy /radiochemotherapy is completed at least 4 and no more than 8 weeks prior to informed consent and post-radiotherapy MRI must not show tumor progression. MRI must be completed within 3 to 6 weeks after radiotherapy.
• Patients must be immunocompetent (i.e., no concomitant treatment with dexamethasone (or equivalent), or receive stable/decreasing steroid levels not exceeding 2 mg/day dexamethasone (or equivalent) during the last 3 days prior to day of clinical screening; no severe lymphopenia)
• ≥18 years old ≤ 70 years old, smoking or non-smoking, of any ethnic origin and gender
• Karnofsky Performance Status ≥ 70
• Ability of patient to understand character and individual consequences of the clinical trial
• Evidence of the informed consent document personally signed and dated by the patient (or a witness in case the patient is unable to write), indicating that the patient has been informed of all pertinent aspects of the study and that the patient consents to participate in the trial.
• Women of child-bearing potential (WOCBP; i.e., those who have not undergone a hysterectomy, bilateral salpingectomy and bilateral oophorectomy or who have not been post-menopausal for at least 24 consecutive months) must have a negative serum pregnancy test (minimum sensitivity 25 IU/L or equivalent units of b-hCG) within 72 hours prior to the start of the IMP.
• Patients of any gender must be willing to practice birth control from the time of enrollment on this study until 12 weeks after last dose of study drug.
• Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.