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

• ClinicalTrials.gov Identifier: NCT04632316
• Recruitment Status: Recruiting
• First Posted: November 17, 2020
• Last Update Posted: May 14, 2021
• Sponsor: Glycostem Therapeutics BV
• Information provided by (Responsible Party): Glycostem Therapeutics BV

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 with no strong indication for 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 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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 33 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase I/IIa Trial to Evaluate the Safety and Efficacy of an Off-the-shelf ex Vivo Cultured Allogeneic NK Cell Preparation in Subjects With Acute Myeloid Leukemia in Complete Morphologic Remission With Measurable Residual Disease and no Strong Indication for Stem Cell Transplantation
• Actual Study Start Date: December 8, 2020
• Estimated Primary Completion Date: April 2023
• Estimated Study Completion Date: April 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

Outcome Measures

Primary Outcome Measures :

1. Safety and tolerability of oNKord® using the cumulative incidence of the adverse events of special interest (AESI) [ Time Frame: 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
2. Efficacy of oNKord® using the cumulative incidence of MRD response as assessed by multiparameter flow cytometry in bone marrow [ Time Frame: 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 :

1. Safety and tolerability of the overall trial treatment (Cy/Flu in combination with up to three oNKord® infusions) using the cumulative incidence of AESI [ Time Frame: 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
2. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on event-free survival (EFS) [ Time Frame: Up to 12 months ]
3. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on cumulative incidence of relapse (CIR) [ Time Frame: Up to 12 months ]
4. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on the duration of MRD response [ Time Frame: Up to 12 months ]
5. Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on overall survival (OS) [ Time Frame: Up to 12 months ]
6. Changes in Quality of Life (EORT QLQ-C30) [ Time Frame: Up to 12 months ]
7. Changes in Quality of Life (SF-36) [ Time Frame: Up to 12 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Kai Pinkernell, MD; +31(0) 412 211 001; medical@glycostem.com

Locations

Belgium

University Hospital Ghent; Recruiting

Ghent, Belgium

University Hospital Leuven; Recruiting

Leuven, Belgium

France

Institut Gustave Roussy; Not yet recruiting

Villejuif, France

Germany

University Medical Center Hamburg-Eppendorf; Recruiting

Hamburg, Germany

Hannover Medical School; Recruiting

Hannover, Germany

Netherlands

Amsterdam UMC; Recruiting

Amsterdam, Netherlands

Switzerland

University Hospital Basel; Recruiting

Basel, Switzerland

University Hospital Zürich; Recruiting

Zürich, Switzerland

Sponsors and Collaborators

Glycostem Therapeutics BV

Investigators

• Principal Investigator: Prof. Dr. Arnold Ganser, MD; Hannover Medical School (MHH), Hannover, Germany

More Information

• Responsible Party: Glycostem Therapeutics BV
• ClinicalTrials.gov Identifier: NCT04632316
• Other Study ID Numbers: WiNK; 2019-003686-17 ( EudraCT Number )
• First Posted: November 17, 2020
• Last Update Posted: May 14, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Glycostem Therapeutics BV:

AML; NK cells; Umbilical cord blood; oNKord; ATMP; Off the shelf; Cell therapy; Immunotherapy; Oncology; Leukemia; Blood cancer

Additional relevant MeSH terms:

Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Neoplasms by Histologic Type; Neoplasms; Cyclophosphamide; Fludarabine; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents, Alkylating; Alkylating Agents; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Myeloablative Agonists