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

NCT ID: NCT06424340

Last Updated: 2025-12-23

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-08-01

Study Completion Date

2028-06-30

Brief Summary

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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

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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

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Leukemia, Myeloid, Acute

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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MB-dNPM1-TCR.1

Biological: MB-dNPM1-TCR.1

Group Type EXPERIMENTAL

MB-dNPM1-TCR.1

Intervention Type BIOLOGICAL

T Cell Receptor (TCR) T cell therapy

Interventions

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MB-dNPM1-TCR.1

T Cell Receptor (TCR) T cell therapy

Intervention Type BIOLOGICAL

Eligibility Criteria

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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 after at least two courses of intensive chemotherapy, decitabine or other standard therapy or
* MRD positive after at least two courses of intensive chemotherapy and not eligible for allogeneic stem cell transplantation or
* Relapsed bone marrow or blood disease after CR after first line treatment and not eligible to undergo allogeneic stem cell transplantation or
* Bone marrow or blood relapse, non-response or MRD positivity after allogeneic stem cell transplantation and not eligible to receive Donor Lymphocyte Infusion (DLI) according to local standards, relapse 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 20% leukemic blasts and at least 0.3x109 T cells/L 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 central nervous system (CNS) disease.
7. 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.
8. Subjects currently on any other IMP (including within the last 30 days before start of treatment).
9. Current use of high dose immunosuppression for immune disorders interfering with T cell function (on discretion of the investigator).
10. Known hypersensitivity against any drug of the mandatory trial procedures.
11. Serum creatinine ≥ 2.0 × ULN or eGFR \< 30 mL/min calculated according to the modified MDRD formula.
12. BMI ≥40
13. Has received vaccination with live vaccines 6 weeks prior to treatment
14. Major surgery less than 30 days before start of treatment.
15. Committal to an institution on judicial or official order.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Miltenyi Biomedicine GmbH

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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C.J.M. Halkes, Dr

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

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Leiden University Medical Center

Leiden, , Netherlands

Site Status RECRUITING

Countries

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Netherlands

Central Contacts

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Jörg Liebmann

Role: CONTACT

Phone: +49151-2034-4392

Email: [email protected]

Facility Contacts

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C.J.M. Halkes, Dr

Role: primary

Other Identifiers

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M-2020-358

Identifier Type: -

Identifier Source: org_study_id