Natural Killer Cell Immunotherapy in Combination With PARP-inhibition in Acute Myeloid Leukemia (NAKIP-AML)

This is an interventional treatment trial for Acute Myeloid Leukemia Read More

Inclusion Criteria:

1. Patients with confirmed diagnosis of AML according to WHO-2016 (Arber, Orazi et al. 2016) (except acute promyelocytic leukemia) with either de novo AML, AML after preceding myelodysplastic or myeloproliferative syndrome (MDS/MPD), and therapy- related AML (t-AML) after previous cytotoxic therapy or radiation are eligible.

   A) Relapsed or Refractory AML with less than 20% bone marrow blasts and less than 20% blasts in peripheral blood.

   B) Rising MRD levels (>3 fold) as detected by either molecular genetics or flow cytometry in patients still in hematologic remission.

2. Patients who received at least one line of AML therapy. This is defined as either stem cell transplantation or intensive AML therapy or palliative AML therapy containing at least one of the following drugs Azacitidine, Decitabine, Cytarabine, Venetoclax or an FLT3 inhibitor..
3. Discontinuation of prior AML treatment before the start of study treatment for at least 107 days for cytotoxic agents and ≥ 53 half-lives for non-cytotoxic / investigational drug treatment preceding the first dose of trial medications.
4. Age ≥ 18 years
5. ECOG ≤2

6. Pregnancy and childbearing potential:

   • Non-pregnant and non-nursing women of childbearing potential must have a negative serum or urine ß-HCG pregnancy test within a sensitivity of at least 25 mIU/mL within 72 hours prior to registration. ("Women of childbearing potential" is defined as a sexually active mature woman who has not undergone a hysterectomy or who has had menses at any time in the preceding 24 consecutive months).
   • Female patients of reproductive age must agree to avoid getting pregnant while on therapy.
   • Women of child-bearing potential must either commit to continued abstinence from heterosexual intercourse or begin highly effective methods (referring to recommendation of the CTFG) of birth control during study and at least 6 months (women), after end of treatment.
   • Men must use a latex condom during any sexual contact with women of childbearing potential, even if they have undergone a successful vasectomy and must agree to avoid to father a child during study and until 6 months after end of treatment.
7. Willingness of patients to adhere to protocol specific requirements and capacity to give written informed consent
8. Ability of patient to understand the character and individual consequences of clinical trial
9. Following receipt of verbal and written information about the study, the patient must provide signed informed consent before any study related activity is carried out.
10. Suitable donor for NK cell transplantation

Exclusion Criteria:

Patients presenting with any of the following criteria will not be included in the trial:

1. Acute promyelocytic leukemia (AML M3)
2. AML in which less than 10% of the blasts express the CD34 surface marker expression as analyzed at the local laboratory.
3. Known central nervous system manifestation of AML

4. Uncontrolled or significant cardiovascular disease, including any of the following:

   • Heart failure NYHA class 3 or 4
   • Left ventricular ejection fraction (LVEF) ≤ 40% by echocardiogram ECHO)
   • History of uncontrolled angina pectoris or myocardial infarction within 12 months prior to screening
   • History of second (Mobitz II) or third-degree heart block or any cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
5. Pregnant or nursing women
6. Chronically impaired renal function (creatinine clearance < 30 ml / min)
7. Organ dysfunction (e.g. liver, kidney, lung, heart) which in the opinion of the treating physician decreases life expectancy to less than three months.
8. Kidney failure with a calculated glomerular filtration rate <30 ml/min or bilirubin >2-fold the upper reference limit of the local laboratory.
9. HIV infection and/or active hepatitis B or C infection (active hepatitis B defined by HBs Ag positivity, anti HBs positivity or anti-HBC positivity, active hepatitis C defined by positive virus load).
10. Evidence or history of severe non-leukemia associated bleeding diathesis or coagulopathy
11. Uncontrolled active infection
12. Concurrent malignancies other than AML with an estimated life expectancy of less than two years
13. Known hypersensitivity to PARP inhibitors
14. Isolated extramedullary manifestation of AML
15. Patients < 100 days after allogeneic stem cell transplantation at the time of screening
16. Expected non-compliance of patient