CLINICAL TRIAL / NCT04310592
Natural Killer Cell (CYNK-001) Infusions in Adults With AML
- Interventional
- Recruiting
- NCT04310592
Contact Information
A Phase I Multi-dose Study of Human Placental Hematopoietic Stem Cell Derived Natural Killer Cells (CYNK-001) With or Without Recombinant Human Interleukin-2 (rhIL-2) in Adults With Primary or Secondary Acute Myeloid Leukemia (AML) in Morphologic Complete Remission With Minimal Residual Disease (MRD) or Relapsed/Refractory (R/R) AML
This study will find the maximum tolerated dose or the maximum planned dose of CYNK-001 which contains natural killer (NK) cells derived from human placental CD34+ cells and culture-expanded. CYNK-001 cells will be given after lymphodepleting chemotherapy. The safety of this treatment will be evaluated, and researchers want to learn if NK cells will help in treating acute myeloid leukemia.
Gender
All
Age Group
18 Years to 80 Years
Accepting Healthy Volunteers
No
Treatment Eligibility Screening Patient Inclusion Criteria
Patients must satisfy the following criteria to be enrolled in the study:
- Patient has eligible disease status:
- 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).
- R/R diagnosis based on confirmed diagnosis with local pathology report
following any reinduction/ salvage therapy ELN guidelines.
1. Relapsed AML are defined as having relapsed after achieving ≥ 1 CR,
including relapse after allogeneic stem cell transplantation (≥ 2 months
after transplant).
2. 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.
3. 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.
4. 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.
- Patient with prior central nervous system involvement by malignancy are eligible
provided that it has been treated and cerebral spinal fluid is clear for at least 2
weeks prior to start of Lymphodepletion Regimen.
- (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.
For the purposes of this study, MRD positivity is defined as greater than or equal to
0.1% blasts detected by MFC on BMA by the Sponsor-selected Central MRD analysis
laboratory, where assay sensitivity allows for a Lower Limit of Detection (LOD) of 1 x
10-4 (0.01%) or lower.
- Patient is ≥ 18 and ≤ 80 years of age at the time of signing the Study informed
consent form (ICF).
- Patient understands and voluntarily signs the Study ICF prior to any study-related
assessments/procedures are conducted.
- Patient is willing and able to adhere to the study schedule and other protocol
requirements.
- Performance status of Eastern Cooperative Oncology Group (ECOG) ≤ 2.
- Ability to be off immunosuppressive drugs for at least 3 days prior to the CYNK-001
infusion. Steroids at the equivalent of no more than 7.5 mg prednisone per day are
permissible.
- Female of childbearing potential (FCBP)* must not be pregnant and agree to not
becoming pregnant for at least 28 days following the CYNK-001. FCBP must agree to
use an adequate method of contraception during the treatment period.
- FCBP is a female who: 1) has achieved menarche at some point, 2) has not
undergone a hysterectomy or bilateral oophorectomy or 3) has not been naturally
postmenopausal (amenorrhea following cancer therapy does not rule out
childbearing potential) for at least 24 consecutive months (i.e., has had
menses at any time in the preceding 24 consecutive months).
- Male Patients must agree to use a condom during sexual contact for at least 28 days
following the last infusion of CYNK-001, even if he has undergone a successful
vasectomy.
Treatment Eligibility Screening Patient Exclusion Criteria
The presence of any of the following will exclude the Patient from enrollment:
- Patient has any significant medical condition, laboratory abnormality, or
psychiatric illness that would prevent the Patient from participating in the study.
- Patient has any condition including the presence of laboratory abnormalities which
places the Patient at unacceptable risk if he or she were to participate in the
study.
- Patient has any condition that confounds the ability to interpret data from the
study.
- Patient has bi-phenotypic acute leukemia.
- Patient has acute promyelocytic leukemia (APL).
- Patient has inadequate organ function as defined below at time of Treatment
Eligibility Period:
1. Patient has aspartate aminotransferase (AST), alanine aminotransferase (ALT),
or alkaline phosphatase ≥ 2.5 x the upper limit of normal (ULN).
2. Estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m2 as calculated
using the Modification of Diet in Renal Disease Study equation (Levey, 2006) or
history of an abnormal eGFR < 60 and a decline of > 15 mL/min/1.73 m2 below
normal in the past year.
3. Patient has a bilirubin level > 2 mg/dL (unless Patient has known Gilbert's
disease).
- Patient has had prior treatment with biologic antineoplastic agents less than 7 days
before first CYNK-001 infusion and at least 5 half-lives. (Exception will be granted
for monoclonal antibodies that are known to have long half-lives, in which case a
minimum of 2 weeks from last dose will be required). For agents that have known AEs
occurring beyond these specified days after administration, this period must be
extended beyond the time during which acute AEs are known to occur. Treating
physicians are encouraged to discuss cases with the Medical Monitor.
- Patient is pregnant or breastfeeding.
- Patient has new or progressive pulmonary infiltrates or pleural effusion large
enough to be detected by chest x-ray or CT scan within 2 weeks of first CYNK-001
infusion.
- Patient has active autoimmune disease other than controlled connective tissue
disorder or those who are not on active therapy.
- Patient has had a Bone Marrow transplant < 60 days prior to screening or plans to
have a transplant within the 28 day period following the first CYNK-001 infusion.
- Patient has a history of malignancy other than AML or other underlying hematologic
conditions such as myelodysplastic syndromes (MDS) or myeloproliferative neoplasms
(MPN) unless the Patient has been free of disease for greater than 3 years prior to
CYNK 001 infusion. Exceptions will include the following malignancies:
1. Basal cell carcinoma of the skin
2. Squamous cell carcinoma of the skin
3. Carcinoma in situ of the cervix
4. Carcinoma in situ of the breast
5. Incidental biological finding of prostate cancer (TNM stage of T1a or T1b)
6. Superficial bladder cancer
7. For patients with therapy-related AML, the underlying malignancy which led to
secondary AML must be stabilized (not progressing) and not under active
treatment.
- Patient has a history of severe asthma and is presently on chronic medications or
has a history of other symptomatic pulmonary disease.
- Patient has the following prior history of GVHD:
Acute GVHD: Subjects with prior history of acute GVHD where signs and/or symptoms did not
completely resolve (no clinical signs/symptoms and not on more than 7.5 mg of predinsone
per day Chronic GVHD: Subjects with prior history of chronic GVHD where signs and/or
symptoms did not completely resolve (no clinical signs/symptoms and not on more than 7.5
mg of prednisone per day) within 90 days of ongoing immunosuppression.
- Patient has an untreated chronic infection or has received treatment of any
uncontrolled or progressive infection with systemic antibiotics within 2 weeks prior
to first CYNK-001 infusion. Prophylactic antibiotic, antiviral, and antifungal
medication are permissible.
- Patient has any other organ dysfunction (CTCAE Version 5.0 Grade 3 or greater) that
will interfere with the administration of the therapy according to this protocol.
- Patient has a resting left ventricular ejection fraction (LVEF) of < 40% obtained by
echocardiography or multi-gated acquisition scan (MUGA).
- Patient was treated with an investigational product within 28 days of first CYNK-001
infusion. Patient must no longer be a participant in the previous interventional
study at the time of CYNK-001 infusion. (Patients who are under survival follow-up
or observation associated with a study are permitted, and if treatment information
is collected for this period, "Investigational Study" must be used to capture the
study treatment.).
- Hematologic Diseases
- Leukemia