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Patients must satisfy the following criteria to be enrolled in the study |
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Patient has eligible disease status |
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Primary or Secondary acute myeloid leukemia (AML) Patients in first of second Morphological Complete Remission (CR), Morphological Complete Remission with incomplete hematologic recovery (CRi), or Morphologic Leukemia-free State (MLFS) as defined by the European LeukemiaNet (ELN) recommendations for AML Response Criteria (Dohner, 2017) |
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R/R diagnosis based on confirmed diagnosis with local pathology report following any reinduction/ salvage therapy ELN guidelines |
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Relapsed AML are defined as having relapsed after achieving ≥ 1 CR, including relapse after allogeneic stem cell transplantation (≥ 2 months after transplant) |
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Refractory AML, defined as not achieving CR, CRi, or MLFS after 2 or more cycles of induction therapy (primary refractory) or not achieving CR after treatment for relapsed AML |
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Secondary AML (MDS transformation): Secondary AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML |
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Treatment-related AML: Treatment-related AML patients are eligible to participate if they have received a minimum of one prior line of treatment for AML |
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Patient with prior central nervous system involvement by malignancy are eligible |
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(MRD positive population only): Patient is minimal residual disease (MRD) positive, as assessed on bone marrow aspirate (BMA) by Multiparameter Flow Cytometry (MFC) at time of Treatment Eligibility assessment |
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provided that it has been treated and cerebral spinal fluid is clear for at |
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least 2 weeks prior to start of Lymphodepletion Regimen |
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For the purposes of this study, MRD positivity is defined as greater than or equal to 0.1% |
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blasts detected by MFC on BMA by the Sponsor-selected Central MRD analysis laboratory |
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where assay sensitivity allows for a Lower Limit of Detection (LOD) of 1 x 10-4 (0.01%) or |
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lower |
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Patient is ≥ 18 and ≤ 80 years of age at the time of signing the Study informed |
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consent form (ICF) |
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Patient understands and voluntarily signs the Study ICF prior to any study-related |
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assessments/procedures are conducted |
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Patient is willing and able to adhere to the study schedule and other protocol |
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requirements |
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Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2 |
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Ability to be off immunosuppressive drugs for at least 3 days prior to the CYNK-001 |
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infusion. Steroids at the equivalent of no more than 7.5 mg prednisone per day are |
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permissible |
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Female of childbearing potential (FCBP) must not be pregnant and agree to not |
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becoming pregnant for at least 28 days following the CYNK-001. FCBP must agree to use |
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an adequate method of contraception during the treatment period |
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FCBP is a female who: 1) has achieved menarche at some point, 2) has not |
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undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally |
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postmenopausal (amenorrhea following cancer therapy does not rule out |
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childbearing potential) for at least 24 consecutive months (i.e., has had menses |
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at any time in the preceding 24 consecutive months) |
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Male Patients must agree to use a condom during sexual contact for at least 28 days |
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following the last infusion of CYNK-001, even if he has undergone a successful |
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vasectomy |
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The presence of any of the following will exclude the Patient from enrollment
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Patient has any condition that confounds the ability to interpret data from the study
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Patient has bi-phenotypic acute leukemia
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Patient has acute promyelocytic leukemia (APL)
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Patient is pregnant or breastfeeding
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Basal cell carcinoma of the skin
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Squamous cell carcinoma of the skin
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Carcinoma in situ of the cervix
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Carcinoma in situ of the breast
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Incidental biological finding of prostate cancer (TNM stage of T1a or T1b)
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Patient has any significant medical condition, laboratory abnormality, or psychiatric
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illness that would prevent the Patient from participating in the study
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Patient has any condition including the presence of laboratory abnormalities which
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places the Patient at unacceptable risk if he or she were to participate in the study
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Superficial bladder cancer
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Patient has inadequate organ function as defined below at time of Treatment
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Eligibility Period
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Patient has aspartate aminotransferase (AST), alanine aminotransferase (ALT), or
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alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN)
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Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as calculated
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using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or
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history of an abnormal eGFR < 60 and a decline of > 15 mL/min/1.73 m2 below
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normal in the past year
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Patient has a bilirubin level > 2 mg/dL (unless Patient has known Gilbert's
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disease)
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Patient has had prior treatment with biologic antineoplastic agents less than 7 days
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before first CYNK-001 infusion and at least 5 half-lives. (Exception will be granted
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for monoclonal antibodies that are known to have long half-lives, in which case a
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minimum of 2 weeks from last dose will be required). For agents that have known AEs
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occurring beyond these specified days after administration, this period must be
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extended beyond the time during which acute AEs are known to occur. Treating
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physicians are encouraged to discuss cases with the Medical Monitor
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Patient has new or progressive pulmonary infiltrates or pleural effusion large enough
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to be detected by chest x-ray or CT scan within 2 weeks of first CYNK-001 infusion
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Patient has active autoimmune disease other than controlled connective tissue disorder
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or those who are not on active therapy
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Patient has had a Bone Marrow transplant < 60 days prior to screening or plans to have
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a transplant within the 28 day period following the first CYNK-001 infusion
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Patient has a history of malignancy other than AML or other underlying hematologic
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conditions such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms
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(MPN) unless the Patient has been free of disease for greater than 3 years prior to
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CYNK 001 infusion. Exceptions will include the following malignancies
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For patients with therapy-related AML, the underlying malignancy which led to
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secondary AML must be stabilized (not progressing) and not under active
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treatment
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Patient has a history of severe asthma and is presently on chronic medications or has
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a history of other symptomatic pulmonary disease
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Patient has uncontrolled graft versus host disease (GVHD) or GVHD requiring treatment
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with corticosteroids
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Patient has an untreated chronic infection or has received treatment of any
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uncontrolled or progressive infection with systemic antibiotics within 2 weeks prior
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to first CYNK-001 infusion. Prophylactic antibiotic, antiviral, and antifungal
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medication are permissible
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Patient has any other organ dysfunction (CTCAE Version 5.0 Grade 3 or greater) that
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will interfere with the administration of the therapy according to this protocol
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Patient has a resting left ventricular ejection fraction (LVEF) of < 40% obtained by
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echocardiography or multi-gated acquisition scan (MUGA)
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Patient was treated with an investigational product within 28 days of first CYNK-001
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infusion. Patient must no longer be a participant in the previous interventional study
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at the time of CYNK-001 infusion. (Patients who are under survival follow-up or
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observation associated with a study are permitted, and if treatment information is
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collected for this period, "Investigational Study" must be used to capture the study
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treatment.)
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