WiNK is a Phase I/IIa trial to evaluate the safety and efficacy of oNKord® in 33 adults with
acute myeloid leukemia (AML) who are in morphologic complete remission with residual
measurable disease and with no strong indication for hematopoietic stem cell transplantation.
WiNK is a prospective 2-stage, open-label, single arm, multicenter Phase I/IIa trial to
evaluate the safety and efficacy of oNKord®, an off-the-shelf, ex vivo-cultured allogeneic NK
cell preparation, in 33 adults with acute myeloid leukemia (AML) who are in morphologic
complete remission (CR) with residual measurable disease (MRD) and with no strong indication
for allogeneic hematopoietic stem cell transplantation (allo-HSCT).
Following informed consent and eligibility procedures, subjects enrolled in the trial will
receive a lymphodepleting conditioning regimen consisting of cyclophosphamide and fludarabine
(Cy/Flu) followed by up to 3 oNKord® infusions 4 days apart.
Stage A of the trial (dose escalation stage) is designed to assess the safety and
tolerability of up to 3 oNKord® infusions, 4 days apart, in 3 cohorts of 3 subjects, and to
determine the oNKord® recommended Phase II dose (RP2D) to be used in Stage B.
Stage B of the trial (expansion stage) will evaluate the safety, tolerability and efficacy of
oNKord® at the RP2D in 24 subjects.
All subjects treated with oNKord® will be followed up until 12 months after the start of
treatment. Eligibility criteria for participation in the trial and follow-up duration are the
same for subjects in both Stage A and Stage B.
Inclusion Criteria:
1. Male or female subjects ≥ 18 years old
2. Subjects with a diagnosis of AML and related precursor neoplasms according to the WHO
2016 classification (excluding acute promyelocytic leukemia), including secondary AML
after an antecedent hematological disease (e.g. myelodysplastic syndrome) and
therapy-related AML
3. Subjects who have achieved morphologic CR, including CRi and complete clinical
remission, with MRD documented at screening, as assessed by centralized MFC, after one
or two courses of remission induction chemotherapy and who have completed
consolidation chemotherapy or who achieved morphologic CR with documented MRD with
hypomethylating agents or other relevant appropriate therapies
4. Life expectancy ≥ 6 months at screening
5. Adequate renal and hepatic functions within 14 days of study screening, unless clearly
disease related, as indicated by the following laboratory values:
1. Serum creatinine ≤ 3 times the upper limit of normal (ULN) and estimated
glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2
2. Serum total bilirubin < 2.0 mg/dl, unless due to Gilbert's syndrome
3. Alanine transaminase (ALT) ≤ 2.5 x ULN
6. Karnofsky Status ≥ 50%
7. Male subjects with partners who are women of childbearing potential must use an
effective contraceptive method during the trial and for a minimum of 6 months after
trial treatment, or have undergone successful vasectomy at least 6 months prior to
entry into the trial (confirmed by semen analysis).
8. Female subjects of childbearing potential must have a negative serum pregnancy test at
screening and agree to use an effective contraceptive method during the trial and for
a minimum of 6 months after trial treatment.
9. Able to understand and willing to provide written informed consent to participate in
the trial
10. Affiliation to a national health insurance scheme (according to applicable local
requirements)
Exclusion Criteria:
1. Subjects proceeding to allogeneic HSCT, i.e. subject is a suitable candidate for
allogeneic HSCT according to the investigator's assessment and donor is expected to be
available in a timely manner
2. Subjects having received prior allogeneic HSCT
3. Subjects with acute promyelocytic leukemia
4. Diagnosis of any previous or concomitant malignancy is an exclusion criterion, except
when the subject completed treatment (chemotherapy and/or surgery and/or radiotherapy)
with curative intent for this malignancy at least 6 months prior to enrolment
5. Blast crisis of chronic myeloid leukemia
6. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes,
uncontrolled hypertension, active or uncontrolled infection) including abnormal
laboratory values, that could compromise compliance with the trial protocol or cause
unacceptable safety risks
7. Antibodies against HLA (anti-HLA) present
8. Seronegativity for Epstein-Barr Virus (EBV)
9. Known allergy to any of the components of oNKord® (e.g., dimethyl sulfoxide [DMSO]) or
to any of the drugs to be administered in the preparative regimen to oNKord® infusion
10. Contraindication to any of the drugs to be administered in the conditioning regimen or
oNKord® infusion. This includes Cy, Flu, and medications associated with prophylaxis
of AEs
11. Cardiac dysfunction as defined by:
1. Myocardial infarction within the last 3 months of trial entry, or
2. Reduced left ventricular function with an ejection fraction < 40% as measured by
multi-gated acquisition (MUGA) scan or echocardiogram (echo) within 28 days
before screening, or
3. Unstable angina, or
4. New York Heart Association (NYHA) Class IV congestive heart failure, or
5. Unstable cardiac arrhythmias
12. Pulmonary dysfunction as defined by oxygen saturation < 90% on room air. Pulmonary
function test (PFT) is required only in the case of symptomatic or prior known
impairments within 28 days before screening - with pulmonary function < 50% corrected
diffusing capacity of the lung for carbon monoxide (DLCO) and forced expiratory volume
in 1 second (FEV1)
13. Major surgery within 4 weeks prior to screening or a major wound that has not fully
healed
14. Vaccination with live, attenuated vaccines within 4 weeks prior to screening
15. Immunosuppressive drugs for concomitant disease. Subject must be able to be off
prednisone or other immunosuppressive medications for at least 3 days prior to the
start of Cy/Flu regimen
16. History of stroke or intracranial hemorrhage within 6 months prior to screening
17. Active infections (viral, bacterial or fungal) that requires specific therapy. Acute
anti-infectious therapy must have been completed within 14 days prior to trial
treatment
18. History of human immunodeficiency virus (HIV) or active infection with hepatitis B
virus (HBV) or hepatitis C virus (HCV)
19. Current concomitant chemotherapy, radiation therapy, or immunotherapy
20. Positive pregnancy test or breastfeeding for women of childbearing potential
21. Participation in another interventional clinical trial within 4 weeks prior to trial
enrolment or participation in a concomitant interventional clinical trial
22. Any serious concomitant medical condition, medication or therapy which could, in the
opinion of the Investigator, compromise participation in the trial
23. Subjects under legal protection measure (guardianship, trusteeship or safeguard of
justice) and/or inability or unwillingness to comply with the requirements and
procedures of this trial
