A Trial to Evaluate the Safety and Efficacy of oNKord® in Subjects With Acute Myeloid Leukemia

• Status: Recruiting
• Trial end date: 2023-04-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Glycostem Therapeutics BV
• Treatments: Cyclophosphamide; Fludarabine

Criteria

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