Pentixather; Yttrium-90 for Non-Hodgkin lymphoma

Inclusion criteria

• {"criterion_text":"- Histologically proven diagnosis of one of the following active measurable lymphoproliferative malignancies (as defined in chapter 10.1): a) Multiple myeloma (progression after conventional chemotherapy, at least one proteasome inhibitor and one immunomodulatory drug, and high-dose chemotherapy with autoSCT, not currently suitable for allogeneic hematopoietic stem cell transplantation [alloSCT]) b) Aggressive B- and T-NHL including heavily pretreated transformed indolent lymphoma (tNHL) (refractory or relapsed disease after extensive pretreatment with min. 2 regimes, at least one including an anti-CD20 antibody, or after standard high-dose chemotherapy with autoSCT), not currently suitable for alloSCT\n- Written informed consent\n- Inclusion of patients with preceded CAR-T cell therapy is allowed but not a perquisite if such a therapy is not indicated or available at the time point of inclusion\n- Positive 68Ga -Pentixafor PET/CT imaging. In patients with MM 68Ga-Pentixafor-PET/CT may be replaced by 68Ga-Pentixafor-PET/MR\n- Bone marrow aspirate and biopsy (according to clinical routine from last lymphom/myelom specific therapy or 3 - 4 months prior to Baseline) for assessment of pathology, cytology and immunohistochemistry and/or flow cytometry for CXCR4 (CD184) expression\n- Availability of CD34+ peripheral blood hematopoietic stem cells (CD34+ HSC), > 2x106 CD34+HSC / kg body weight) prior to enrolment, obtained during a previous treatment line, including HSC intended for backup use\n- Age ≥ 18 years\n- Eastern cooperative oncology group (ECOG) performance status 0-1 and life expectancy > 3 months and deemed fit for high-dose chemotherapy and autologous stem-cell transplantation\n- Adequate hematopoetic, hepatic (ALAT/ASAT <5x ULN, total Bilirubin <2.5x ULN), renal (CreaCl>40ml/min), cardiac and pulmonary function, excluding organ dysfunctions associated with the underlying disease.\n- Women of childbearing potential (WOCBP) must be non-lactating and surgically sterile or using a highly effective method of birth control and have a negative pregnancy test. Acceptable methods of birth control with a low failure rate (i.e. less than 1% per year) when used consistently and correct are for example implants, injectables, combined oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence (defined as refraining from heterosexual intercourse during the clinical trial) or vasectomized partner. Those contraceptive measures should be applied for 30 days after visit 3 Men with child bearing potential (CBP) must either use a condom, must be vasectomized or stay sexual abstinent. Contraception for WOCBP – as above mentioned – should be considered. Those contraceptive measures should be applied for 90 days after visit 3."}

Exclusion criteria

• {"criterion_text":"- Evidence of active concurrent malignant disease\n- Evidence of rapid progress of underlying diseases with severely limited life expectancy (< 3 months)\n- Evidence of significant, uncontrolled acute or chronic concomitant diseases that could affect compliance with the protocol or interpretation of results including contraindications against CT-/MRI-/PET-Scans or against myeloablative therapy followed by autoSCT\n- Study participants with discrepant lesions in FDG PET cannot be included\n- Uncontrolled active or chronic infection, including hepatitis B and/or C (Anti-HbS, HbSAG) and HIV (Anti-HIV)\n- Patients with a history of psychiatric illness or condition that could interfere with their ability to understand the requirements of the clinical trial\n- Previous or concurrent participation in another clinical study involving trial medication within the preceding 12 weeks (prior to Baseline) or previous participation in this clinical trial\n- Pregnancy or breast-feeding women\n- Known hypersensitivity to the IMP or NIMP/AxMP or any agent given in association with this clinical trial"}

Primary endpoints

• {"endpoint_text":"- Phase I: Determination of maximum tolerated dose (MTD)","definition_or_measurement_approach":"Determination of MTD by escalation of 90Y-Pentixather in combination with high-dose chemotherapy according to SOC (e.g. Melphalan, Treosulfan) followed by autologous stem-cell transplantation (autoSCT)."}
• {"endpoint_text":"- Phase II: ORR","definition_or_measurement_approach":"Overall response rate (ORR) of the treatment regimen established in the Phase I part."}

Secondary endpoints

• {"endpoint_text":"- Phase I: The dosimetric analysis for the assessment of the radiation dose received by the patient.","definition_or_measurement_approach":"Dosimetric analysis to assess the radiation dose received by the patient (radiation dose estimation)."}
• {"endpoint_text":"- Phase II: Median PFS, OS, hematopoietic recovery (measured with the time course of CBCs)","definition_or_measurement_approach":"Median progression-free survival (PFS) and overall survival (OS); hematopoietic recovery assessed by time course of complete blood counts (CBCs)."}
• {"endpoint_text":"- Safety Endpoints: Frequency and severity of adverse events","definition_or_measurement_approach":"Safety evaluated by frequency and severity (grading) of adverse events."}

Germany

Earliest CTIS Part Ii Submission Date

02-09-2024

Latest Decision Or Authorization Date

14-10-2024

Processing Time Days

42

Number Of Sites

3

Number Of Participants

38

Primary sponsor

Full Name

Klinikum rechts der Isar der TU Muenchen AöR

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Germany