Leukemia, Myeloid, AcutePhase 1/2NCT06424340
MB-dNPM1-TCR.1 in Relapsed/Refractory AML
A Phase 1/2 study testing MB-dNPM1-TCR.1 in people with Leukemia, Myeloid, Acute, run by Miltenyi Biomedicine GmbH at 1 site in Netherlands.
Trial summary
The goal of this Phase I/II, single arm, prospective, open label, dose escalation trial is to assess safety, feasibility and efficacy of ex vivo expanded autologous T cells genetically modified to express a T cell receptor (TCR) specific for dNPM1 peptides restricted to human leukocyte antigen (HLA) A*02:01 in… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Leukemia, Myeloid, Acute
- What is being tested?
- MB-dNPM1-TCR.1
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 29 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Aug 2024to Jun 2028
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years
- Patients must be able to understand and be willing to give signed informed consent
- Relapsed or refractory acute myeloid leukemia (last disease staging within 4 weeks prior to screening) without standard treatment options defined as:
- No morphological CR or extramedullary AML after at least two courses of intensive chemotherapy, decitabine or other standard therapy or
- MRD positive after at least two courses of intensive chemotherapy or other standard therapy and not eligible for allogeneic stem cell transplantation or
- Relapsed bone marrow or blood disease or extramedullary AML after CR after first line treatment and not eligible to undergo allogeneic stem cell transplantation or
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- Bone marrow, blood, extramedullary AML relapse or non-response or MRD positivity after allogeneic stem cell transplantation and not eligible to receive Donor Lymphocyte Infusion (DLI) according to local standards, relapse or MRD positive after DLI.
- Positive for HLA-A*02:01 according to genotyping results.
- AML has NPM1 mutation which is recognized by dNPM1-TCR.1 and for which a specific Q-PCR is available for disease monitoring.
- Number of circulating WBC above 1x109/L with less than 50% leukemic blasts and 0.03 x 109 CD8+ T cells/L.
- Life expectancy of at least 3 months.
- ECOG performance status 0-3.
- Negative pregnancy test in women of childbearing potential.
- For fertile men and women, agreement to use highly effective contraceptive methods during the trial.
Who cannot join
- Pregnant or breast feeding women.
- Active infection with HIV-1, HIV-2, HBV, HCV, HTLV-I, HTLV-II, SARS-CoV-2 or Treponema Pallidum.
- Any clinically significant, advanced or unstable disease or inadequate main organ function that may put the patient at increased risk for severe complications of trial participation at the discretion of the investigator.
- Use of systemic immune suppression including, but not limited to:
- immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of 0.5 mg prednisone/kg body weight per day, or higher). Inhaled steroid and physiological replacement for adrenal insufficiency are allowed.
- Unwillingness or inability to comply with procedures required in this clinical trial protocol.
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- Uncontrolled life-threatening infections or uncontrolled disseminated intravascular coagulation; however, if these problems resolve, the start of treatment can be initiated on a delayed schedule.
- Subjects currently on any other IMP (including within the last 30 days before start of treatment).
- Current use of high dose immunosuppression for immune disorders interfering with T cell function (on discretion of the investigator).
- Known hypersensitivity against any drug of the mandatory trial procedures.
- Serum creatinine ≥ 2.0 × ULN or eGFR < 30 mL/min calculated according to the modified MDRD formula.
- BMI ≥40
- Has received vaccination with live vaccines 6 weeks prior to treatment
- Major surgery less than 30 days before start of treatment.
- Committal to an institution on judicial or official order.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site, 1 recruiting
- Recruiting
Leiden University Medical Center
Leiden, 2333
C.J.M. Halkes, Dr
About this study
Official title: A Phase I/II Trial of MB-dNPM1-TCR.1 in HLA-A*02:01-positive Patients With Relapsed or Refractory NPM1-mutated AML to Determine Safety and Obtain First Data on Efficacy
The goal of this Phase I/II, single arm, prospective, open label, dose escalation trial is to assess safety, feasibility and efficacy of ex vivo expanded autologous T cells genetically modified to express a T cell receptor (TCR) specific for dNPM1 peptides restricted to human leukocyte antigen (HLA) A*02:01 in patients with relapsed or refractory AML.
Read the detailed description
The investigational medicinal product (IMP) MB-dNPM1-TCR.1 is designed to effectively target malignant myeloid cells in patients suffering from relapsed or refractory Acute Myeloid Leukemia (AML) with mutated Nucleophosmin. Autologous T cells will be genetically engineered using a lentiviral vector to express a T cell receptor (TCR) specific for certain dNPM1 peptides restricted to human leukocyte antigen (HLA) A*02:01. The dNPM1-TCR transduced T cells target specifically the HLA/dNPM1 peptide complex on the cell surface of leukemic myeloid cells and eliminate these. During the treatment, the patients will undergo a leukapheresis, a lymphodepleting chemotherapy and an administration of the expanded dNPM1-TCR transduced T cells.
Phase I: Since this is a first in human trial the primary goal in phase I is to establish the recommended dose of MB-dNPM1-TCR.1 for phase II. We assess the maximum tolerated dose (MTD) with toxicity defined as patients experiencing dose limiting toxicity (DLT) until day 28 after infusion of MB-dNPM1-TCR.1. Therefore a BOIN trial design will be used to guide dose escalation and de-escalation decisions in phase I.
Phase II: The second phase will evaluate the efficacy and safety in patients treated with the recommended dose from phase I. The phase II part follows a Simon's 'minimax' two stage design.
- Conditions
- Leukemia, Myeloid, Acute
- Being tested
- MB-dNPM1-TCR.1
- Medical subject headings
- Leukemia, Myeloid, Acute
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MB-dNPM1-TCR.1Biological
T Cell Receptor (TCR) T cell therapy
| Study group | Role | What they receive |
|---|---|---|
| MB-dNPM1-TCR.1 | Experimental | Biological: MB-dNPM1-TCR.1 Receives: Biological: MB-dNPM1-TCR.1 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint Phase I
Maximum tolerated dose (MTD), as identified by a Bayesian Optimal Interval (BOIN) design at a target toxicity rate of 30%, with toxicity defined as patients experiencing dose limiting toxicity (DLT) until day 28 (week 4) after infusion of MB-dNPM1-TCR.1.
Measured: day 28
Primary endpoint Phase II
BOR rate to the treatment with MB-dNPM1-TCR.1 assessed at any time within the first 3 months (12 weeks) after infusion as described above.
Measured: week 12
Secondary outcomes (7)
Persistence
Percentage and total number of MB-dNPM1-TCR+ cells in peripheral blood and/or bone marrow over time.
Measured: from day 6 to week 96
Best objective response (BOR)
Best objective response (BOR) during 12 weeks after infusion of MB-dNPM1-TCR.1. BOR is defined in relation to disease activity before thawing the leukapheresis for manufacturing (day -18 and -15).
Measured: week 12
Overall survival (OS)
Overall survival (OS) defined as the time between the date of infusion of MB-dNPM1-TCR.1 and the date of death from any cause.
Measured: up to week 96
Progression-free survival (PFS)
Progression-free survival (PFS) defined as the time between the date of infusion of MB-dNPM1-TCR.1 and the date of objective disease progression or death from any cause whichever occurs first.
Measured: up to week 96
Duration of response (DOR)
Duration of response (DOR), defined as the time between the date of the first objective response (CRMRD- CR, CRi, MLFS, PR, SD) and the date of assessment of relapse or the date of death due to AML, whichever occurs first.
Measured: up to week 96
Safety and toxicity
Safety and toxicity assessment of MB-dNPM1-TCR.1 per (serious) adverse events ((S)AE) reporting.
Measured: up to week 96
Feasibility to manufacture
Proportion of thawed apheresis products, from which MB-dNPM1-TCR.1 drug products are produced.
Measured: Day 0
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 May 2024
- Study start1 Aug 2024
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Leukemia, Myeloid, AcuteStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 29 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Miltenyi Biomedicine GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- C.J.M. Halkes, Dr, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06424340
- Sponsor's protocol ID
- M-2020-358
- Status last verified
- Dec 2025
- First submitted
- 16 May 2024
- Last updated
- 16 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of MB-dNPM1-TCR.1 in HLA-A*02:01-positive Patients With Relapsed or Refractory NPM1-mutated AML to Determine Safety and Obtain First Data on Efficacy
- ClinicalTrials.gov ID
- NCT06424340
- Acronym / sponsor ID
- M-2020-358
- Conditions
- Leukemia, Myeloid, Acute
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 29 participants (estimated)
- Lead sponsor
- Miltenyi Biomedicine GmbHIndustry (pharma, biotech, devices)
- Study start
- 1 Aug 2024 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 22 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this Phase I/II, single arm, prospective, open label, dose escalation trial is to assess safety, feasibility and efficacy of ex vivo expanded autologous T cells genetically modified to express a T cell receptor (TCR) specific for dNPM1 peptides restricted to human leukocyte antigen (HLA) A*02:01 in patients with relapsed or refractory AML.
Detailed description
The investigational medicinal product (IMP) MB-dNPM1-TCR.1 is designed to effectively target malignant myeloid cells in patients suffering from relapsed or refractory Acute Myeloid Leukemia (AML) with mutated Nucleophosmin. Autologous T cells will be genetically engineered using a lentiviral vector to express a T cell receptor (TCR) specific for certain dNPM1 peptides restricted to human leukocyte antigen (HLA) A*02:01. The dNPM1-TCR transduced T cells target specifically the HLA/dNPM1 peptide complex on the cell surface of leukemic myeloid cells and eliminate these. During the treatment, the patients will undergo a leukapheresis, a lymphodepleting chemotherapy and an administration of the expanded dNPM1-TCR transduced T cells.
Phase I: Since this is a first in human trial the primary goal in phase I is to establish the recommended dose of MB-dNPM1-TCR.1 for phase II. We assess the maximum tolerated dose (MTD) with toxicity defined as patients experiencing dose limiting toxicity (DLT) until day 28 after infusion of MB-dNPM1-TCR.1. Therefore a BOIN trial design will be used to guide dose escalation and de-escalation decisions in phase I.
Phase II: The second phase will evaluate the efficacy and safety in patients treated with the recommended dose from phase I. The phase II part follows a Simon's 'minimax' two stage design.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| MB-dNPM1-TCR.1 | Experimental | Biological: MB-dNPM1-TCR.1Biological: MB-dNPM1-TCR.1 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age ≥ 18 years
- Patients must be able to understand and be willing to give signed informed consent
- Relapsed or refractory acute myeloid leukemia (last disease staging within 4 weeks prior to screening) without standard treatment options defined as:
- Positive for HLA-A*02:01 according to genotyping results.
- AML has NPM1 mutation which is recognized by dNPM1-TCR.1 and for which a specific Q-PCR is available for disease monitoring.
Key exclusion criteria (15 listed)
- Pregnant or breast feeding women.
- Active infection with HIV-1, HIV-2, HBV, HCV, HTLV-I, HTLV-II, SARS-CoV-2 or Treponema Pallidum.
- Any clinically significant, advanced or unstable disease or inadequate main organ function that may put the patient at increased risk for severe complications of trial participation at the discretion of the investigator.
- Use of systemic immune suppression including, but not limited to:
- immunosuppressive agents such as cyclosporine or corticosteroids (at an equivalent dose of 0.5 mg prednisone/kg body weight per day, or higher). Inhaled steroid and physiological replacement for adrenal insufficiency are allowed.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MB-dNPM1-TCR.1T Cell Receptor (TCR) T cell therapy | Biological | MB-dNPM1-TCR.1 |
Primary outcome
Primary endpoint Phase I
Time frame: day 28
Maximum tolerated dose (MTD), as identified by a Bayesian Optimal Interval (BOIN) design at a target toxicity rate of 30%, with toxicity defined as patients experiencing dose limiting toxicity (DLT) until day 28 (week 4) after infusion of MB-dNPM1-TCR.1.
Primary endpoint Phase II
Time frame: week 12
BOR rate to the treatment with MB-dNPM1-TCR.1 assessed at any time within the first 3 months (12 weeks) after infusion as described above.
7 secondary outcomes
Persistence
Time frame: from day 6 to week 96
Best objective response (BOR)
Time frame: week 12
Overall survival (OS)
Time frame: up to week 96
Progression-free survival (PFS)
Time frame: up to week 96
Duration of response (DOR)
Time frame: up to week 96
Safety and toxicity
Time frame: up to week 96
Feasibility to manufacture
Time frame: Day 0
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Apr 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
C.J.M. Halkes, Dr principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MB-dNPM1-TCR.1 in people with Leukemia, Myeloid, Acute, run by Miltenyi Biomedicine GmbH at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 16 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jörg Liebmann (+49151-2034-4392, clinicaltrials.gov@miltenyi.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint Phase I (time frame: day 28). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Apr 2026.