Overview
Sponsor-declared trial summary
Phase
Therapeutic exploratory (Phase II)
Status
Ongoing, recruitment ended
Participants planned
64
Countries
1
Sites
11
Malignant B-cell lymphoma
Determination of the ORR in the experimental arm and comparison to historic results (Analysis will be based on Lugano -Criteria ).
Key facts
- Sponsor
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 10 Feb 2021 → ongoing
- Decision date (initial)
- 2024-08-22
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- No
- Vulnerable population
- Yes
- Funding sources
- Incyte Corporation United States
External identifiers
- EU CT number
- 2024-514775-17-00
- EudraCT number
- 2019-002373-59
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Safety, Efficacy
Determination of the ORR in the experimental arm and comparison to historic results (Analysis will be based on Lugano -Criteria ).
Secondary objectives 3
- Determination of CR-Rate, PFS, OS
- ORR based on Cheson 2007-criteria
- Determination of QoL (global QoL, physical functioning, Fatigue)
Conditions and MedDRA coding
Malignant B-cell lymphoma
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 21.0 | PT | 10003903 | B-cell lymphoma refractory | 100000004864 |
Study design 1 period
| # | Title | Allocation | Blinding | Roles blinded | Arms |
|---|---|---|---|---|---|
| 1 | Period 1 All patients enrolled in this trial will receive the established Non Hodgkin Lymphoma
chemotherapy regime of R-Gem/Ox (non-IMP)plus the IMP Tafasitamab for induction therapy, and
Tafasitamab will be administered as consolidation therapy up to 22 months afterwards.
|
2 | None | Tafasitamab: All patients enrolled in this trial will receive the established Non Hodgkin Lymphoma chemotherapy regime of R-Gem/Ox (non-IMP)plus the IMP Tafasitamab for induction therapy, and Tafasitamab will be administered as consolidation therapy up to 22 months afterwards. |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 11
- Histologically proven diagnosis of a) diffuse large cell B-cell lymphoma, and other aggressive B-cell lymphomas according to the WHO 2016 revision (specified in detail in the protocol) b) follicular lymphoma grade 3B and c) transformed indolent B-cell lymphoma (not more than 20 % of the patient population) according to the WHO classification (central pathology review)
- Relapsed disease or refractory disease, at least one but no more than two prior treatment lines
- age ≥ 18 years
- No curative option available (age ≥ 65yr and/or HCT-CI Score > 2) or s.p. HDT
- At least 1 measurable tumor mass (>1.5 cm x >1.0 cm) or bone marrow infiltration
- Adequate bone marrow reserve: a) Platelets of at least 100 000/μl b) absolute neutrophil count of at least 1000/μl
- Adequate hepatic and renal function: a) Alanine aminotransferase (ALT) <2.5 x upper limit of normal (ULN) b) Aspartate aminotransferase (AST) <2.5 x upper limit of normal (ULN) c) Total bilirubin <1.5 x upper limit of normal (ULN) unless related to lymphoma
- Measured or calculated eGFR >50 ml/min (institutional standard)
- Eastern Cooperative Oncology Group (ECOG) performance Status ≤2, unless tumor associated and expected to improve on treatment
- Signed informed consent
- Adequate contraception (if needed)
Exclusion criteria 15
- CNS involvement (brain MRI is required only in cases of clinically suspicious involvement)
- no adequate pretreatment (R-CHOP-like, or BR for initial indolent lymphoma)
- systemic treatment within last 6 weeks, steroids for bridging are allowed
- prior allogeneic transplantation prior anti CD19 CAR T-cell therapy or prior Tafasitamab therapy
- pregnant or breast-feeding women
- severe concomitant disease (e.g. uncontrolled arterial hypertension, heart failure (NYHA III-IV), uncontrolled diabetes mellitus, pulmonary fibrosis, uncontrolled hyperlipoproteinemia)
- Prolongation of QTc interval > 450 ms, demonstrated in electrocardiogramm (two separate or one in triplicate) or family history for Long QT-syndrome
- active uncontrolled infections
- HIV positivity
- Hepatitis C
- active Hepatitis B, patients with HBs-Ag positivity and no measurable HBV-DNA are eligible
- Medical or psychological condition that would not permit completion of the trial or signing of informed consent
- Diagnosed or treated for a malignancy other than NHL except: a) adequately treated non-melanoma skin cancer b) curatively treated in-situ cancer of the cervix c) ductal carcinoma in situ (DCIS) of the breast d) other solid tumors curatively treated with no evidence of disease for >2 years e) prostate cancer with a life expectancy of more than 2 years
- Concurrent treatment with another investigational agent or within the last 6 weeks prior to treatment initiation. Concurrent participation in non-treatment studies is not excluded
- Known intolerance to any of the study drugs or to any drug with similar chemical structure or to any excipient present in the pharmaceutical form of the investigational medicinal product
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- ORR of the regimen within the first 8 treatment cycles
Secondary endpoints 8
- ORR (Cheson 2007-criteria)
- Progression free survival (Lugano)
- Overall survival
- CR-Rate (Lugano)
- Best response (Lugano)
- Quality of Life measured with EORTC QLQ C30 and NHL-HG29 (global QoL, physical functioning, fatigue)
- ORR in separate GCB vs. non GCB-analysis is planned
- Safety Endpoints: Safety and tolerability as measured by rate of AE, SAE compared between Arm A and B
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 1
MINJUVI 200 mg powder for concentrate for solution for infusion
PRD9171980 · Product
- Active substance
- Tafasitamab
- Substance synonyms
- MOR00208, HUMANIZED FC ENGINEERED MONOCLONAL ANTIBODY AGAINST CD19, MOR-208, XMAB-5574
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS USE
- Max daily dose
- 12 mg/kg milligram(s)/kilogram
- Max total dose
- 504 mg/kg milligram(s)/kilogram
- Max treatment duration
- 22 Month(s)
- Authorisation status
- Authorised
- ATC code
- L01FX12 — -
- Marketing authorisation
- EU/1/21/1570/001
- MA holder
- INCYTE BIOSCIENCES DISTRIBUTION B.V.
- MA country
- EU
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 3
SCP128961 · ATC
- Active substance
- Oxaliplatin
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 100 mg/m2 milligram(s)/sq. meter
- Max total dose
- 800 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 112 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01XA03 — OXALIPLATIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP872361 · ATC
- Active substance
- Rituximab
- Substance synonyms
- CT-P10, PF-05280586, ABP 798, BI 695500, JHL1101, HLX01
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 375 mg/m2 milligram(s)/sq. meter
- Max total dose
- 3000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 112 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01FA01 — RITUXIMAB
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1128788 · ATC
- Active substance
- Gemcitabine Hydrochloride
- Substance synonyms
- GEMCITABINE (AS HYDROCHLORIDE), 4-AMINO-1-[(2R,4R,5R)-3,3-DIFLUORO-4-HYDROXY-5-(HYDROXYMETHYL)OXOLAN-2-YL]PYRIMIDIN-2-ONE HYDROCHLORIDE
- Route of administration
- INTRAVENOUS INFUSION
- Max daily dose
- 1000 mg/m2 milligram(s)/sq. meter
- Max total dose
- 8000 mg/m2 milligram(s)/sq. meter
- Max treatment duration
- 112 Day(s)
- Authorisation status
- Authorised
- ATC code
- L01BC05 — GEMCITABINE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Sponsor organisation
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Address
- Langenbeckstrasse 1, Oberstadt Oberstadt
- City
- Mainz
- Postcode
- 55131
- Country
- Germany
Scientific contact point
- Organisation
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Contact name
- Sponsor contact point clinical trials
Public contact point
- Organisation
- Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
- Contact name
- Sponsor contact point clinical trials
Locations
1 EU/EEA country · 11 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Germany | Ongoing, recruitment ended | 64 | 11 |
| Rest of world | — | 0 | — |
Investigational sites
Staedtisches Klinikum Karlsruhe gGmbH
Medizinische Klinik III, Moltkestrasse 90, Weststadt, Karlsruhe
OncoResearch Lerchenfeld GmbH
Onkologie, Lerchenfeld 14, Uhlenhorst, Hamburg
Universitaetsklinikum Schleswig-Holstein AöR
Medizinische Klinik II, Arnold-Heller-Strasse 3, Brunswik, Kiel
Klinikum Der Landeshauptstadt Stuttgart gKAöR
Tumorzentrum Eva Mayr-Stihl, Kriegsbergstrasse 60, Mitte, Stuttgart
Universitaetsklinikum Frankfurt AöR
Medizinische Klinik II, Theodor-Stern-Kai 7, 60590, Frankfurt Am Main
Universitaetsklinikum Augsburg
II. Medizinische Klinik, Stenglinstrasse 2, Kriegshaber, Augsburg
Universitaetsmedizin der Johannes Gutenberg-Universitaet Mainz KöR
III. Medizinische Klinik, Hämatologie und Onkologie, Langenbeckstrasse 1, Oberstadt, Mainz
Marien Hospital Herne
Studienambulanz, Hölkeskampring 40, 44625, Herne
Rotkreuzklinikum Muenchen gGmbH
III. Medizinische Abteilung, Nymphenburger Strasse 163, Neuhausen-Nymphenburg, Munich
Pi.Tri-Studien GmbH
Ambulantes Therapiezentrum Hämatologie/Onkologie, Ebertplatz 12, 77654, Offenburg
St. Johannes-Hospital
Klinik f. Innere Medizin II/ Onkozentrum, Amalienstraße 21a, 44137, Dortmund
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Germany | 2021-02-10 | 2021-07-01 | 2024-07-01 |
Oversight and notifications
Regulatory notifications under CTR Articles 38, 52, 53, 54 and 77
Temporary halts 1 · Art. 38 CTR
Temporary halt TH-42605
- Halt date
- 2024-07-01
- Member states concerned
- Germany
- Publication date
- 2024-08-26
- Reason
- Feasibility (recruitment issues etc.)
- Benefit-risk balance changed
- No
- Treatment stopped
- No
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 7 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocoll 2024-514775-17-00 public | 2.1 |
| Recruitment arrangements (for publication) | K1_Recruitment Arrangements | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults | 2.0 |
| Subject information and informed consent form (for publication) | L2_SIS and ICF adults short version | 1.0 |
| Subject information and informed consent form (for publication) | L3_Patient ID Card | 1.1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Minjuvi March 2022 | 1 |
| Synopsis of the protocol (for publication) | D1_Protocol synopsis german 2024-514775-17-00 | 2.0 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-08-06 | Germany | Acceptable with conditions 2024-08-16
|
2024-08-22 |