Clinical Trials /

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

NCT04632316

Description:

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 complete morphologic remission with residual measurable disease and with no strong indication for hematopoietic stem cell transplantation.

Related Conditions:
  • Acute Myeloid Leukemia
  • Secondary Acute Myeloid Leukemia
  • Therapy-Related Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: WiNK
  • SECONDARY ID: 2019-003686-17
  • NCT ID: NCT04632316

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Cyclophosphamide-Fludarabine (Cy/Flu)oNKord®
oNKord®oNKord®

Purpose

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 complete morphologic remission with residual measurable disease and with no strong indication for hematopoietic stem cell transplantation.

Detailed Description

      WiNK is a prospective 2-stage, open-label, single arm, multicentre 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 complete
      morphologic remission with residual measurable disease and with no strong indication for
      hematopoietic stem cell transplantation.

      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.
    

Trial Arms

NameTypeDescriptionInterventions
oNKord®ExperimentalAllogeneic ex vivo-generated Natural Killer (NK) cells from CD34+ umbilical cord blood progenitor cells
  • Cyclophosphamide-Fludarabine (Cy/Flu)
  • oNKord®

Eligibility 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 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:

               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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and tolerability of oNKord® using the cumulative incidence of the adverse events of special interest (AESI)
Time Frame:Up to 12 months
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Safety and tolerability of the overall trial treatment (Cy/Flu in combination with up to three oNKord® infusions) using the cumulative incidence of AESIs
Time Frame:Up to 12 months
Safety Issue:
Description: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
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Efficacy of the overall trial treatment (Cy/Flu in combination with oNKord® at RP2D) on overall survival (OS)
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Changes in Quality of Life (EORT QLQ-C30)
Time Frame:Up to 12 months
Safety Issue:
Description:
Measure:Changes in Quality of Life (SF-36)
Time Frame:Up to 12 months
Safety Issue:
Description:

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Glycostem Therapeutics BV

Trial Keywords

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

Last Updated

November 23, 2020