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

Sponsor

Glycostem Therapeutics BV (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04632316

Collaborator

(none)

Enrollment

Locations

Arm

27.7

Anticipated Duration (Months)

3.3

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief 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 who are currently not proceeding to allogeneic hematopoietic stem cell transplantation.

Condition or Disease	Intervention/Treatment	Phase
Acute Myeloid Leukemia	Drug: Cyclophosphamide-Fludarabine (Cy/Flu) Drug: oNKord®	Phase 1/Phase 2

Detailed Description

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 who are currently not proceeding to 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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

33 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Prospective Phase I/IIa, Open-label, Multicenter Trial to Evaluate the Safety and Efficacy of oNKord®, an Off-the-shelf, ex Vivo-cultured Allogeneic NK Cell Preparation, in Subjects With Acute Myeloid Leukemia Who Are in Morphologic Complete Remission With Measurable Residual Disease and Who Are Currently Not Proceeding to Allogeneic Hematopoietic Stem Cell Transplantation

Actual Study Start Date :

Dec 8, 2020

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Apr 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: oNKord® Allogeneic ex vivo-generated Natural Killer (NK) cells from CD34+ umbilical cord blood progenitor cells	Drug: Cyclophosphamide-Fludarabine (Cy/Flu) Lymphodepleting conditioning regimen Drug: oNKord® Allogeneic ex vivo-generated Natural Killer (NK) cells from CD34+ umbilical cord blood progenitor cells

Arm

Intervention/Treatment

Experimental: oNKord®

Allogeneic ex vivo-generated Natural Killer (NK) cells from CD34+ umbilical cord blood progenitor cells

Drug: Cyclophosphamide-Fludarabine (Cy/Flu)

Lymphodepleting conditioning regimen

Drug: oNKord®

Allogeneic ex vivo-generated Natural Killer (NK) cells from CD34+ umbilical cord blood progenitor cells

Outcome Measures

Primary Outcome Measures

Safety and tolerability of oNKord® using the cumulative incidence of the adverse events of special interest (AESI) [Up to 12 months]
AESI include: Grade 3 to 4 infusion-related toxicity of oNKord®, as rated by CTCAE v5.0; Acute GVHD grade III and IV; CRS and ICANS ≥ Grade 2, as rated by the ASTCT Consensus Grading
Efficacy of oNKord® using the cumulative incidence of MRD response as assessed by centralized assessment in bone marrow [Up to 12 months]
Subjects with responses are defined as MRD negative subjects still in morphologic CR at any time during the follow-up period of the trial after receiving oNKord® at RP2D

Secondary Outcome Measures

Safety and tolerability of the overall trial treatment (Cy/Flu in combination with up to three oNKord® infusions) using the cumulative incidence of AESI [Up to 12 months]
AESI include: Grade 3 to 4 infusion-related toxicity of oNKord® as rated by CTCAE v5.0; Acute GVHD grade III and IV; CRS and ICANS ≥ Grade 2 as rated by the ASTCT Consensus Grading; Hemorrhagic 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 defined as death due to infectious disease
Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on event-free survival (EFS) [Up to 12 months]
Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on cumulative incidence of relapse (CIR) [Up to 12 months]
Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on the duration of MRD response [Up to 12 months]
Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on overall survival (OS) [Up to 12 months]
Changes in Quality of Life (EORT QLQ-C30) [Up to 12 months]
Changes in Quality of Life (SF-36) [Up to 12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Male or female subjects ≥ 18 years old
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
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
Subjects who are currently (at the time of screening) not proceeding to allo-HSCT
Life expectancy ≥ 6 months at screening
Adequate renal and hepatic functions within 14 days of study screening, unless clearly disease related, as indicated by the following laboratory values:
Serum creatinine ≤ 3 times the upper limit of normal (ULN) and estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2
Serum total bilirubin < 2.0 mg/dl, unless due to Gilbert's syndrome
Alanine transaminase (ALT) ≤ 2.5 x ULN
Karnofsky Status ≥ 50%
Seropositivity for EBV
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).
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.
Able to understand and willing to provide written informed consent to participate in the trial
Affiliation to a national health insurance scheme (according to applicable local requirements)

Exclusion Criteria:

Subjects having received prior allogeneic HSCT
Subjects with acute promyelocytic leukemia
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
Blast crisis of chronic myeloid leukemia
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
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
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
Cardiac dysfunction as defined by:
Myocardial infarction within the last 3 months of trial entry, or
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
Unstable angina, or
New York Heart Association (NYHA) Class IV congestive heart failure, or
Unstable cardiac arrhythmias
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)
Major surgery within 4 weeks prior to screening or a major wound that has not fully healed
Vaccination with live, attenuated vaccines within 4 weeks prior to screening
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
History of stroke or intracranial hemorrhage within 6 months prior to screening
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
History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
Subjects who are undergoing or will be undergoing chemotherapy (including HMAs), radiation therapy, targeted therapy or immunotherapy that cannot be finished or stopped at least 1 week prior to initiating the Cy/Flu conditioning regimen
Positive pregnancy test or breastfeeding for women of childbearing potential
Use of other investigational drugs/therapies within 3 weeks prior to trial treatment (within 6 weeks in the case of drugs/therapies with long half-life) or participation in a concomitant interventional clinical trial
Any serious concomitant medical condition, medication or therapy which could, in the opinion of the Investigator, compromise participation in the trial
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

Contacts and Locations

Locations

	Site	City	Country
1	University Hospital Ghent	Ghent	Belgium
2	University Hospital Leuven	Leuven	Belgium
3	Institut Gustave Roussy	Villejuif	France
4	University Hospital Carl Gustav Carus Dresden	Dresden	Germany
5	University Medical Center Hamburg-Eppendorf	Hamburg	Germany
6	Hannover Medical School	Hannover	Germany
7	University Hospital Mainz	Mainz	Germany
8	Amsterdam UMC	Amsterdam	Netherlands
9	University Hospital Basel	Basel	Switzerland
10	University Hospital Zürich	Zürich	Switzerland