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

Prior treatment

• Subjects currently on any other IMP (including within the last 30 days before start of treatment).
• Has received vaccination with live vaccines 6 weeks prior to treatment
• Major surgery less than 30 days before start of treatment.

Other illness

• 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.
• 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.
• 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.

Lab values

• Serum creatinine ≥ 2.0 × ULN or eGFR \< 30 mL/min calculated according to the modified MDRD formula.

Other

• Pregnant or breast feeding women.
• Unwillingness or inability to comply with procedures required in this clinical trial protocol.
• BMI ≥40
• Committal to an institution on judicial or official order.

• 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.