Overview
Sponsor-declared trial summary
MDS with excess blasts, MDS/AML or AML patients
Of phase I of the study is to evaluate the safety and toxicity of the infusion of ex vivo-expanded RNK001 NK cells, both with and without SC IL-2, following a non-myeloablative immunosuppressive conditioning regimen in patients with MDS with excess blasts, MDS/AML or AML. Of phase IIa of the study is to evaluate the e…
Key facts
- Sponsor
- Stichting Radboud universitair medisch centrum
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Neoplasms [C04]
- Trial duration
- 20 Jan 2025 → ongoing
- Decision date (initial)
- 2025-01-20
- Transition trial
- Yes
- Low-intervention
- No
- Rare-disease indication
- Yes
- Vulnerable population
- No
- Funding sources
- KWF Kankerbestrijding
External identifiers
- EU CT number
- 2024-515357-16-00
- EudraCT number
- 2019-001929-27
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Therapy, Others, Efficacy, Pharmacokinetic, Safety
Of phase I of the study is to evaluate the safety and toxicity of the infusion of ex vivo-expanded RNK001 NK cells, both with and without SC IL-2, following a non-myeloablative immunosuppressive conditioning regimen in patients with MDS with excess blasts, MDS/AML or AML.
Of phase IIa of the study is to evaluate the effect of RNK001 NK cell adoptive immunotherapy in combination with SC IL-2 following a non-myeloablative immunosuppressive conditioning regime on disease activity in patients with MDS with excess blasts, AML/MDS or AML.
Conditions and MedDRA coding
MDS with excess blasts, MDS/AML or AML patients
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 1
- -MDS with excess blasts, MDS/AML or AML or defined according to ELN 2022 (including MDS, MDS/AML or AML with mutated TP53); AML may be secondary to prior hematological disorders, including MDS, and/or therapy-related. - Stable or at least non-rapidly progressive disease with or without disease controlling medication. - Patients may belong to any of the following categories: o Relapsed/refractory disease after treatment with intensive chemotherapy, hypomethylating agents, targeted agents, autologous or allo-SCT (at least 6 months ago) and DLI o Newly diagnosed, untreated patients ineligible for allo-SCT - Age ≥ 18 years - WHO performance 0-2 (Appendix 2) - Life expectancy of > 4 months - Written informed consent - Hydrea is allowed as pre-treatment to control blast count until day -3 - Hypomethylating agents decitabine or azacitidine are allowed until day -7 (i.e. last administration >28 days before start chemotherapy).
Exclusion criteria 1
- - Rapid-progressive disease in case of previous therapy (see Appendix 1). - Patients on immunosuppressive drugs or active GvHD - Patients with active infections (viral, bacterial or fungal); acute anti-infectious therapy must have been completed within 7 days prior to study treatment - Severe cardiovascular disease (CTCAE III-IV) - Severe pulmonary dysfunction (CTCAE III-IV) - Severe renal dysfunction (CTCAE III-IV) - Severe hepatic dysfunction (CTCAE III-IV) - Severe neurological or psychiatric dysfunction (CTCAE III-IV) - Patients on concurrent chemotherapy or interferon-alpha treatment - Pregnancy or breastfeeding
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- During the phase I safety study, patients will be evaluated intensively for toxicity caused by the RNK001 NK cell infusions, whether or not followed by SC IL-2, using the CTCAE toxicity criteria and graft versus host disease (GvHD) classification criteria, defining dose limiting toxicities (DLTs). For phase IIa of the study, clinical response to therapy is the main study parameter and will be defined according to European Leukemia Network (ELN) response criteria by day +28 post NK cell adminis.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
Proleukin 18 x 106 IE Poeder voor oplossing voor injectie of infusie
PRD11294442 · Product
- Active substance
- Aldesleukin
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- SUBCUTANEOUS
- Max daily dose
- 6000000 U unit(s)
- Max total dose
- 36000000 U unit(s)
- Max treatment duration
- 6 Day(s)
- Authorisation status
- Authorised
- ATC code
- L03AC01 — ALDESLEUKIN
- Marketing authorisation
- RVG 13354
- MA holder
- IOVANCE BIOTHERAPEUTICS B.V
- MA country
- Netherlands
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD11861601 · Product
- Active substance
- RNK001
- Pharmaceutical form
- DISPERSION FOR INFUSION
- Route of administration
- INTRAVENIOUS INFUSION
- Max daily dose
- 3000000000 U unit(s)
- Max total dose
- 3000000000 U unit(s)
- Max treatment duration
- 1 Day(s)
- Authorisation status
- Not Authorised
- MA holder
- STICHTING RADBOUD UNIVERSITY MEDICAL CENTER
- Paediatric formulation
- No
- Orphan designation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Stichting Radboud universitair medisch centrum
- Sponsor organisation
- Stichting Radboud universitair medisch centrum
- Address
- Geert Grooteplein Zuid 10
- City
- Nijmegen
- Postcode
- 6525 GA
- Country
- Netherlands
Scientific contact point
- Organisation
- Stichting Radboud universitair medisch centrum
- Contact name
- Trialbureau Hematologie
Public contact point
- Organisation
- Stichting Radboud universitair medisch centrum
- Contact name
- Trialbureau Hematologie
Locations
1 EU/EEA country · 1 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Netherlands | Ongoing, recruitment ended | 16 | 1 |
| Rest of world | — | 0 | — |
Investigational sites
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 |
|---|---|---|---|---|---|
| Netherlands | 2025-01-20 | 2025-01-20 | 2025-08-31 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 4 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | D1_Protocol NK4AML v5 2024-515357-16-00 | 5.0 |
| Recruitment arrangements (for publication) | K1_blank_document_Recruitment_arrangements | 0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF NK4AML | 4.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Proleukin | 0 |
Application history
1 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2025-01-06 | Netherlands | Acceptable 2025-01-20
|
2025-01-20 |