A trial to evaluate the safety and efficacy of oNKord® in participants with acute myeloid leukaemia who are in morphologic complete remission with measurable residual disease and who are currently not proceeding to allogeneic hematopoietic stem cell transplantatio
- Conditions
- acute myeloid leukaemiaMedDRA version: 21.0Level: LLTClassification code 10000886Term: Acute myeloid leukemiaSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2019-003686-17-DE
- Lead Sponsor
- Glycostem Therapeutics BV
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 40
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 World Health Organization (WHO) 2016 classification (excluding acute promyelocytic leukemia), including secondary AML after an antecedent hematological disease (e.g. myelodysplastic syndrome) and therapy-related AML
3. a. For cohorts A1, A2, A3, A5 (and cohort B if applicable): Subjects who have achieved morphologic CR, including CRi, and complete clinical remission, with MRD documented at screening, 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 (HMAs) or other relevant appropriate therapies (e.g., HMAs in combination with venetoclax)
b. For cohort A4 (and cohort B if applicable): Subjects with newly diagnosed AML who have achieved morphologic CR, including CRi while undergoing azacitidine-venetoclax standard of care treatment, and who are MRD-positive on the 28th day (+/- 7 days) of at least treatment cycle 3 or later cycles (=3)
4. Subjects who are currently (at the time of screening) not proceeding to allo-HSCT, i.e.:
a. Subjects who have a contraindication for allo-HSCT (e.g., age > 75 years old, diffusing capacity of the lung for carbon monoxide [DLCO] < 60%, left ventricular ejection fraction [LVEF] < 40%, liver cirrhosis, creatinine clearance < 30 mL/min, hematopoietic stem cell transplantation-specific comorbidity index [HCT-CI] = 5); or
b. Subjects who have no contraindication for allo-HSCT but do not proceed:
i. By personal choice; or
ii. Because there is no compatible donor expected to be available in a
timely manner; or
iii. Due to unfavorable patient-specific risk-benefit assessment discussed between the treating physician and the patient and his/her close relatives. Factors taken into consideration include the disease-related risk (risk of relapse, toxicity or other treatment options if any), the patient-related risk (age, comorbidities including the HCT-CI score) and the curative potential of allo-HSCT versus toxicity (treatment intensity, graft versus leukemia effect, non-relapse mortality risk) (Muller and Muller-Tidow 2015)
5. Life expectancy = 6 months at screening
6. Adequate renal and hepatic functions within 14 days of trial 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/1.73 m2
b. Serum total bilirubin < 2.0 mg/dL, unless due to Gilbert’s syndrome
c. Alanine transaminase (ALT) = 2.5 x ULN
7. Karnofsky Status = 50%
8. Seropositivity to Epstein-Barr virus (EBV)
9. 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)
10. 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
11. Able to understand and willing to provide written informed consent to participate i
Subjects who meet any of the following criteria at screening will be excluded from trial entry:
1. Subjects having received prior allo-HSCT
2. Subjects with acute promyelocytic leukemia
3. 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 enrollment
4. Blast crisis of chronic myeloid leukemia
5. 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
6. 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
7. For cohorts A1, A2, A3, A5 (and cohort B if applicable): Contraindication to any of the drugs to be administered in the lymphodepleting conditioning regimen. This includes Cy, Flu, and medications associated with prophylaxis of AEs
8. 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
9. 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 DLCO and forced expiratory volume in 1 second (FEV1)
10. Major surgery within 4 weeks prior to screening or a major wound that has not fully healed
11. Vaccination with live, attenuated vaccines within 4 weeks prior to screening
12. Subjects must be able to be off prednisone or other immunosuppressive medications for concomitant disease for at least 3 days prior to the:
a. Start of the Cy/Flu regimen in cohorts A1, A2, A3, A5 (and cohort B if applicable)
b. First oNKord® infusion in cohort A4 (and cohort B if applicable)
13. History of stroke or intracranial hemorrhage within 6 months prior to screening
14. 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
15. History of human immunodeficiency virus (HIV) or active infection with hepatitis B virus (HBV) or hepatitis C virus (HCV)
16. a. For cohorts A1, A2, A3, A5 (and cohort B if applicable): 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
b. For cohort A4 (and cohort B if applicable): Subjects who are undergoing or will be undergoing chemotherapy (excluding HMAs), radiation therapy, targeted therapy or immunotherapy that cannot be finished or stopped at least 1 week prior to the first oNKord® infusion
17. Positive pregnancy test or breastfeeding for women of childbearing potential
18. Use of other investigational drugs/therapies within 3 we
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method