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

NCT06424340 | Recruiting Phase 1 DMC

• 1 other identifier: M-2020-358
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Leukemia, Myeloid, Acute

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  week 12

Secondary Outcomes (7)

• Persistence

  from day 6 to week 96

• Best objective response (BOR)

  week 12

• Overall survival (OS)

  up to week 96

• Progression-free survival (PFS)

  up to week 96

• Duration of response (DOR)

  up to week 96

Study Arms (1)

MB-dNPM1-TCR.1

EXPERIMENTAL

Biological: MB-dNPM1-TCR.1

Biological: MB-dNPM1-TCR.1

Interventions

MB-dNPM1-TCR.1 BIOLOGICAL

T Cell Receptor (TCR) T cell therapy

MB-dNPM1-TCR.1

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Miltenyi Biomedicine GmbH: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333, Netherlands

RECRUITING

MeSH Terms

Conditions

Leukemia, Myeloid, Acute

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Study Officials

• C.J.M. Halkes, Dr

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jörg Liebmann

CONTACT

+49151-2034-4392; clinicaltrials.gov@miltenyi.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2024
• First Posted: May 22, 2024
• Study Start: August 1, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 16, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)