Indication: Non-Hodgkin lymphomas (NHL) Advanced lymphoproliferative cancers: aggressive B- and T- cell Non-Hodgkin lymphomas (NHL), including heavily pretreated transformed indolent lymphoma (tNHL) and multiple myeloma (MM) as a subgroup of B-cell NHL MedDRA version: 22.0 Level: PT Classification code 10029547 Term: Non-Hodgkin's lymphoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Name: 90Y-Pentixather
Pharmaceutical Form: Solution for injection in vial
INN or Proposed INN: PentixaTher acetate
Other descriptive name: Pentixather
Concentration unit: GBq gigabecquerel(s
Sponsors
Klinikum rechts der Isar der Technischen Universität München
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. 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 2. 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 3. Positive 68Ga -Pentixafor PET/CT imaging. In patients with MM 68Ga-Pentixafor-PET/CT may be replaced by 68Ga-Pentixafor-PET/MR 4. 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 5. 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 6. Age = 18 years 7. 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 8. Adequate hematopoetic, hepatic (ALAT/ASAT 40ml/min), cardiac and pulmonary function, excluding organ dysfunctions associated with the underlying disease. 9. 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 (defined as refraining from heterosexual intercourse during the clinical trial). Contraception for WOCBP – as above mentioned – should be considered. Those contraceptive measures should be applied for 90 days after visit 3. 10. Written informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 8 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Evidence of active concurrent malignant disease 2. Evidence of rapid progress of underlying diseases with severely limited life expectancy (< 3 months) 3. 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 4. Study participants with discrepant lesions in FDG PET cannot be included 5. Uncontrolled active or chronic infection, including hepatitis B and/or C (Anti-HbS, HbS-AG) and HIV (Anti-HIV) 6. Patients with a history of psychiatric illness or condition that could interfere with their ability to understand the requirements of the clinical trial 7. 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 8. Pregnancy or breast-feeding women 9. Known hypersensitivity to the IMP or NIMP/AxMP or any agent given in association with this clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Phase I: The definition of the max. tolerated activity by escalation of 90Y-Pentixather in combination with high dose chemotherapy according to SOC (e.g. Melphalan, Treosulfan) followed by autoSCT. Phase II: to evaluate the overall response rate (ORR) of the treatment regime established in the phase I part of the clinical trial ;Secondary Objective: Phase I: Assessment of the radiation dose received by the patient. Phase II: Median PFS, OS, safety and tolerability, hematopoietic recovery (measured with CBCs) ;Primary end point(s): Phase I: Determination of maximum tolerated dose (MTD) Phase II: ORR ;Timepoint(s) of evaluation of this end point: Phase I: from Baseline to Visit 4 Phase II: 9 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Phase I: The dosimetric analysis for the assessment of the radiation dose received by the patient. Phase II: Median PFS, OS, hematopoietic recovery (measured with the time course of CBCs) ;Timepoint(s) of evaluation of this end point: Phase II: 24 months | — |
Countries
Germany
Contacts
Public ContactHelen Bidner
TUM School of Medicine and Health, Münchner Studienzentrum
Outcome results
None listed