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Clinical Trials in the Netherlands / NCT06424340
Recruiting Phase 1/2

MB-dNPM1-TCR.1 in Relapsed/Refractory AML

NCT06424340 · tracked via the Priya Life Science Netherlands tracker
Phase
Phase 1/2
Started
2024-08-01
Last updated
2026-04-16

Condition(s) studied

Leukemia, Myeloid, Acute

Investigational drug(s) / intervention(s)

MB-dNPM1-TCR.1

MB-dNPM1-TCR.1: T Cell Receptor (TCR) T cell therapy

Study 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 patients with relapsed or refractory AML.

Eligibility

Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria: 1. Age ≥ 18 years 2. Patients must be able to understand and be willing to give signed informed consent 3. 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 * 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. 4. Positive for HLA-A\*02:01 according to genotyping results. 5. AML has NPM1 mutation which is recognized by dNPM1-TCR.1 and for which a specific Q-PCR is available for disease monitoring. 6. Number of circulating WBC above 1x109/L with less than 50% leukemic blasts and 0.03 x 109 CD8+ T cells/L. 7. Life expectancy of at least 3 months. 8. ECOG performance status 0-3. 9. Negative pregnancy test in women of childbearing potential. 10. For fertile men and women, agreement to use highly effective contraceptive methods during the trial. Exclusion Criteria: 1. Pregnant or breast feeding women. 2. Active infection with HIV-1, HIV-2, HBV, HCV, HTLV-I, HTLV-II, SARS-CoV-2 or Treponema Pallidum. 3. 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. 4. 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. 5. Unwillingness or inability to comply with procedures required in this clinical trial protocol. 6. 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. 7. Subjects currently on any other IMP (including within the last 30 days before start of treatment). 8. Current use of high dose immunosuppression for immune disorders interfering with T cell function (on discretion of the investigator). 9. Known hypersensitivity against any drug of the mandatory trial procedures. 10. Serum creatinine ≥ 2.0 × ULN or eGFR \< 30 mL/min calculated according to the modified MDRD formula. 11. BMI ≥40 12. Has received vaccination with live vaccines 6 weeks prior to treatment 13. Major surgery less than 30 days before start of treatment. 14. Committal to an institution on judicial or official order.

Primary outcome measure(s)

Trial sites (1)

FacilityCityRegionStatus
Leiden University Medical Center Leiden Netherlands Recruiting

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Official registry record

This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.

View NCT06424340 on ClinicalTrials.gov ↗ ← All trials in the Netherlands