BERUBICIN HYDROCHLORIDE for Primary central nervous system lymphoma|Non-Hodgkin lymphoma with CNS involvement

Inclusion criteria

• {"criterion_text":"- Written informed consent prior to any study-related procedure, and willing and able to comply with the protocol and aware of the investigational nature of this study.\n- At least 18 years of age.\n- Confirmation of a diagnosis: a. For patients with primary central nervous system lymphoma i. A diagnosis of central nervous system lymphoma confirmed by a pathologist on brain tissue or on the meningeal or cranial nerve lesion b. For patients with non-Hodgkin’s lymphoma i. A diagnosis of non-Hodgkin’s lymphoma confirmed by a pathologist on the lymph node biopsy. ii. Confirmed involvement of the CNS (brain, meninges, cranial nerves, eyes and/or spinal cord) at diagnosis (concomitant to extra-CNS disease) or relapse after conventional chemo(-immuno)therapy iii. Diagnosis of CNS involvement either by biopsy or CSF cytopathologic or cytometric examination. Neuroimaging alone is acceptable when a stereotactic biopsy is formally contraindicated or when the disease has been previously histologically documented in other areas and the CNS localization is concomitant with a diffuse progression of systemic disease.\n- No previous treatment with high-dose methotrexate-based chemotherapy. For patients with non-Hodgkin’s lymphoma up to two courses of R-CHOP are allowed as upfront therapy in patients with advanced disease. The decision is made by the Investigator.\n- No prior investigational therapy within 4 weeks before the first dose of study drug\n- The Eastern Cooperative Oncology Group (ECOG) Performance Status 0-3.\n- Eligible for chemotherapy based on adequate bone marrow function cardiac, kidney and liver function as defined by the following laboratory guidelines, subject to the Investigator’s discretion: a. Hematopoietic function: platelet count ≥75 x 109/L, hemoglobin ≥8 g/dL, absolute neutrophil count (ANC) ≥1 x 109/L, unless due to organ involvement b. Cardiac function: ejection fraction LVEF ≥45%. c. Renal function: creatinine ≤2 x the upper limit of normal (ULN), unless due to organ involvement. d. Hepatic function: bilirubin ≤3 × ULN (excluding Gilbert's Syndrome, for which bilirubin must be ≤4 × ULN), and/or aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase <3 × ULN, unless due to organ involvement or Gilbert’s Syndrome.\n- Women of childbearing potential must agree to practice a highly effective method of contraception beginning at least 28 days before the start of treatment until at least 3,5 months after the last dose of study drug. Male study patients and their female sexual partners of childbearing potential must agree to practice a highly effective method of contraception starting from the time of informed consent until at least 3,5 months after the last dose of study drug. a. A woman of childbearing potential is defined as a woman who is not permanently sterilized or postmenopausal. Postmenopausal is defined as 12 months with no menses without an alternative medical cause. b. Women of childbearing potential must have a negative serum or urine pregnancy test. c. A highly effective method of birth control is defined as one which results in a low failure rate (i.e., less than 1% per year) when used consistently and correctly, such as implants, injectables, combined oral contraceptives, some intrauterine devices (IUDs), sexual abstinence, or vasectomized partner. For patients using a hormonal contraceptive method, information regarding all medications being administered to the patient and their potential effect on the contraceptive should be addressed."}

Exclusion criteria

• {"criterion_text":"- Unable or not willing to comply with the protocol regulations.\n- Patients that are pregnant, lactating, or not using adequate contraception.\n- Contraindications to the use of anthracyclines.\n- Presence of uncontrolled, active viral, bacterial, or fungal infection.\n- Severe heart failure (NYHA III/IV) with EF <45%, severe renal disease (CKD ≥ 4) and / or severe liver disease or cirrhosis (bilirubin > 3 mg/dL or ALT / AST > 3x ULN) not due to organ involvement.\n- History of unstable coronary artery disease CCS>2 or myocardial infarction within the last 6 months.\n- Previous treatment with autologous or allogeneic stem cells/bone marrow transplantation.\n- Presence of human immunodeficiency virus (HIV) infection and of detectable hepatitis C virus RNA (HCV-RNA) and/or hepatitis B virus surface antigen (HBsAg) and/or hepatitis B virus DNA (HBV-DNA).\n- Concurrent malignancies (with exceptions of BCC and cervical cancer in situ). Previous malignancies are accepted if surgically cured or if there was no evidence of disease in the last 2 years at a regular follow-up.\n- Any other serious medical condition which, in the opinion of the Investigator, could impair the ability of the patient to participate in the trial or comply with the study protocol and follow-up schedule."}

Primary endpoints

• {"endpoint_text":"- To evaluate the safety and tolerability of Berubicin in combination with other cytostatic agents and to determine the recommended Phase 2 dose (RP2D) of Berubicin","definition_or_measurement_approach":""}

Secondary endpoints

• {"endpoint_text":"- To evaluate Progression Free Survival (PFS), defined as the time interval from the date of the first study drug administration to the date of first documentation of progressive disease (PD) or death (whichever occurs first) at 2 years in patients with Primary Central Nervous System Lymphoma and secondary Non-Hodgkin’s Lymphoma with CNS involvement treated with Berubicin-containing chemotherapeutic regimens","definition_or_measurement_approach":"PFS defined as time from first study drug administration to first documentation of progressive disease or death, assessed at 2 years."}
• {"endpoint_text":"- To assess overall response rate (ORR), defined as the proportion of participants who achieved a CR or PR at the end of therapy as assessed by the Investigator according to the most recent \"Lugano Response Criteria for NHL\" [1] or the \"Response Criteria of the International Primary CNS Lymphoma Collaborative Group - IPCG\" [2] criteria","definition_or_measurement_approach":"ORR = proportion achieving complete response (CR) or partial response (PR) at end of therapy per Investigator using Lugano or IPCG criteria."}
• {"endpoint_text":"- To assess the effect of Berubicin on overall survival (OS) defined as the time interval from the date of the first study drug administration to the date of death at 2 years","definition_or_measurement_approach":"OS defined as time from first study drug administration to date of death, assessed at 2 years."}
• {"endpoint_text":"- Proportion of patients achieving CR at 12 months","definition_or_measurement_approach":""}
• {"endpoint_text":"- Proportion of patients achieving PR at 12 months","definition_or_measurement_approach":""}
• {"endpoint_text":"- To assess the effect of Berubicin on event-free survival (EFS), defined as the length of time from the initiation of study drug administration to disease progression, death, or discontinuation of treatment for any reason (e.g., toxicity, intolerance, disease-related conditions, or failure to respond)","definition_or_measurement_approach":"EFS defined as time from initiation of study drug to disease progression, death, or discontinuation of treatment for any reason."}
• {"endpoint_text":"- To evaluate the concentration of complement factors (C3, C4, C5), CRP protein, and circulating miRNA particles in subjects’ plasma and CSF fluid using genomic microarray assessment","definition_or_measurement_approach":"Concentrations assessed in plasma and CSF using genomic microarray assessment."}
• {"endpoint_text":"- To confirm the pharmacokinetic (PK) profile of Berubicin and its metabolite, berubicinol","definition_or_measurement_approach":"PK profiling of Berubicin and its metabolite berubicinol (methods not specified in provided text)."}

Poland

Latest Decision Or Authorization Date

18-11-2024

Number Of Sites

1

Number Of Participants

60

Primary sponsor

Full Name

Pomeranian Medical University

Organisation Type

Educational Institution

Country Of Registered Address

Poland

Third parties

• {"country":"","full_name":"Medical Research Agency","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"CNS PHARMACEUTICALS, INC.","duties_or_roles":"","organisation_type":""}