acute myeloid leukaemia
Conditions
Sponsors
Glycostem Therapeutics BV
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: To be eligible to participate in this trial, subjects must meet ALL of the following eligibility 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 leukaemia), including secondary AML after an antecedent haematological disease (e.g. myelodysplastic syndrome) and therapy-related AML 3. Subjects who have achieved CMR, 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 CMR 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: a. Serum creatinine = 3 times the upper limit of normal (ULN) and estimated glomerular filtration rate (eGFR) = 30 ml/min/1.73m2 b. Serum total bilirubin =65 years) yes F.1.3.1 Number of subjects for this age range 16
Exclusion criteria
Exclusion criteria: Subjects who meet any of the following criteria at screening will be excluded from trial entry: 1. Subjects proceeding to allogeneic HSCT, i.e. subject is a suitable candidate for allogeneic HSCT and donor is expected to be available in a timely manner 2. Subjects having received prior allogeneic HSCT 3. Subjects with acute promyelocytic leukaemia 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 leukaemia 6. Concurrent severe and/or uncontrolled medical condition (e.g. uncontrolled diabetes, infection, hypertension, pulmonary disease etc.) 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: a. Myocardial infarction within the last 3 months of trial entry, or b. 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 c. Unstable angina, or d. New York Heart Association (NYHA) Class IV congestive heart failure, or e. 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 haemorrhage 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objectives are: •The primary safety objective is to evaluate the safety and tolerability of up to three infusions of oNKord® •The primary efficacy objective is to assess the cumulative incidence of MRD response, following the infusion of oNKord® at the RP2D ;Secondary Objective: The secondary objectives are: •In Stage A, to determine the RP2D of oNKord® •To evaluate the safety and tolerability of the overall trial treatment (combination of the Cy/Flu conditioning regimen and up to three oNKord® infusions) •To further assess the efficacy of the overall trial treatment (combination of the Cy/Flu conditioning regimen and oNKord® at RP2D) on EFS, duration of MRD response, CIR and OS •To evaluate the effect of the overall trial treatment (combination of the Cy/Flu conditioning regimen and oNKord® at RP2D) on quality of life (QoL) ;Primary end point(s): Safety and Tolerability: To evaluate the safety and tolerability of oNKord® using the cumulative incidence of the adverse events of special interest (AESI), including: •Grade 3-to 4 infusion-related toxicity of oNKord®, as rated by the National Cancer Institute (NCI)’s Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 •Acute GVHD grade III and IV •CRS = Grade 2, as rated by the ASTCT Consensus Grading for Cytokine Release Syndrome •ICANS = Grade 2, as rated by the ASTCT Consensus Grading for Neurologic Toxicity Associated with Immune Effector Cells (see Appendix C) Efficacy: To evaluate the efficacy of oNKord® using: •The cumulative incidence of MRD response as assessed by multiparameter flow cytometry (MFC) in bone marrow on Day +14 and at 1, 2, 3, 6, 9 and 12 months post-RP2D oNKord® infusion. Subjects with responses are defined as MRD negative subjects still in CMR at any time during the follow-up period of the trial after receiving oNKord® at RP2D ;Timepoint(s) of evaluation of this end point: Safety & tolerability: at screening, D-6 D-5, D-4, D-3, D0, D1, (D5, D8,) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Safety and Tolerability: To evaluate the safety and tolerability of the overall trial treatment (Cy/Flu in combination with up to three oNKord® infusions) using the cumulative incidence of AESIs, including: • Grade 3-to 4 infusion-related toxicity of the overall trial treatment, as rated by CTCAE v5.0 • Acute GVHD grade III and IV / Extensive chronic GVHD • CRS = Grade 2, as rated by the ASTCT Consensus Grading for Cytokine Release Syndrome • ICANS = Grade 2, as rated by the ASTCT Consensus Grading for Neurologic Toxicity Associated with Immune Effector Cells • Haemorrhagic cystitis • Death related to the overall trial treatment • Incidence and severity of viral, fungal, and bacterial infections with onset during the first two months following conditioning initiation, including viral reactivations, and Infection Related Mortality (IRM) defined as death due to infectious disease Efficacy: To evaluate the efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) by assessing: • EFS, defined as the time from enrolment until disease relapse (morphologic and/or clinical relapse) after CMR or death due to any cause, whichever occurs first • CIR, defined as the cumulative incidence of relapse throughout the course of the trial • Duration of MRD response, defined as duration between MRD negativity to returning to MRD positivity, as assessed by MFC • OS, defined as the time from enrolment until death from any cause • Changes in QoL using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and SF-36 questionnaires, assessed at 1, 3 and 12 months post-treatment compared to baseline Exploratory Endpoints • Analysis of biomarkers predictive of response may include: o Analysis of responders and non-responders, as assessed by the efficacy primary endpoint, in relation to secondary efficacy endpoints o Targeted DNA sequencing of commonly mutated genes in AML, performed by next generation sequencin | — |
Countries
Belgium, France, Germany, Netherlands, Switzerland
Contacts
Public ContactPavlina Topalova
SMS-oncology
Outcome results
None listed