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Clinical Trial 20039

Cancer Type: Malignant Hematology
Interventions:NKR-2 ()

Study Type: Treatment
Phase of Study: Phase I/II
Investigators:

  • David Sallman

Call 813-745-6100
or 1-800-679-0775
Overview

Study Title

An Open-Label, Phase I/II Study to Assess the Safety and Clinical Activity of NKR-2 Treatment Administration after a Non-Myeloablative Preconditioning Chemotherapy in Relapse/Refractory Acute Myeloid Leukemia or Myelodysplastic Syndrome Patients.

Summary

This open-label Phase I study aims at assessing primarily the safety of the NKR-2 treatment administered after a non-myeloablative preconditioning regimen in r/r AML/MDS participants This Phase I study will contain two different sequential segments The first segment will determine the recommended investigational treatment option (schedule of preconditioning and NKR-2 dose) and the second segment will expand to a larger number of r/r AML/MDS participants

Objective

The safety of the NKR-2 treatment administration in r/r AML/MDS patients after a non-myeloablative preconditioning.

Inclusion Criteria

  • The participant must have signed the written ICF and must accept that, beyond the treatment period, and the treatment follow-up period, he/she will have to be monitored for a Long-Term Safety Follow-Up (LTSFU) for up to 15 years after enrollment
  • The participant must be ≥ 18 and ≤ 75 years old at the time of signing the ICF
  • The participant must not be eligible for standard of care therapy and have one of the following hematological malignancy:
  • A confirmed relapsed or refractory acute myeloid leukemia (AML) (ie ≥ 5% blasts in bone marrow or in peripheral blood) after at least one prior therapy defined as either
  • Recurrence of disease after a first complete remission (CR1) and not eligible for a second course of induction therapy, or
  • Recurrence of disease after a second complete remission (CR2), or
  • Failure to achieve CR after induction chemotherapy Note: Participant with AML M3 are excluded >A confirmed myelodysplastic syndrome (MDS) with:
  • Revised International Prognostic Scoring System (R-IPSS) criteria for Intermediate, High-risk or Very High-risk disease or refractory anemia with excess blasts by WHO (ie ≥ 5% blasts in bone marrow or ≥ 2% blasts in peripheral blood) or MDS with TP53 mutation as detected by next-generation sequencing (NGS)
  • Failure of prior treatment with at least 4 cycles of azacitidine or decitabine defined as no response to treatment, loss of response at any time point, or progressive disease/intolerance to therapy
  • The absolute peripheral blast count should be >Revised Recommendations of the International Working Group for Diagnosis, Standardization of Response Criteria, for AML participants,
  • IWG 2006 Uniform Response Criteria for participants with Higher-Risk MDS 7 The participant must have an Eastern Cooperative Oncology Group (ECOG) performance status below or equal to 2
  • The participant must have adequate hepatic and renal functions as assessed by standard laboratory criteria
  • The participant must have a left ventricular ejection fraction (LVEF) of more than or equal to 40%, as determined by echocardiography or a multigated acquisition (MUGA) scan
  • The participant must have a good pulmonary function with a Forced Expiratory Volume in the first second (FEV-1)/Forced Vital Capacity (FVC) more than or equal to 07 with FEV-1 more than or equal to 50% predicted (GOLD 1 or 2 severity) as determined by the spirometry performed at baseline , unless related to the AML/MDS disease as judged by the Investigator
  • Women of child-bearing potential and men must agree to use effective contraception before, during and for at least 2 months after the last study treatment administration
  • The participant must, in the opinion of the Investigator, be able to adhere with the study visit schedule and all study procedures described in this protocol

  • Exclusion Criteria

  • The participant has a confirmed or history of tumor involvement in the central nervous system
  • Participants who have received any cancer therapy (investigational agent or not), including but not limited to chemotherapy, small molecules, monoclonal antibodies (eg, immune checkpoint blockade therapies), or radiotherapy within 2 weeks before the planned day for the apheresis
  • Participants who are planned to receive, concurrently receiving or have received any investigational agent within 3 weeks before the planned day for the first NKR-2 administration
  • Participant is under systemic immunosuppressive drugs, unless specific cases authorized per protocol
  • Participants who have received prior allogeneic stem cell transplantation or chimeric antigen receptor therapy
  • Participants who are presenting persistent toxicities greater than or equal to CTCAE grade 2 caused by previous cancer therapy (except for clinically non-significant toxicities, such as alopecia)
  • Presence of any indwelling catheter or drain (eg, percutaneous nephrostomy tube, indwelling foley catheter, biliary drain, or pleural/peritoneal/pericardial catheter) may be permissible unless they have a catheter-associated infection that cannot be cleared with antibiotics Ommaya reservoirs and dedicated central venous access catheters such as a Port-a-Cath, peripherally inserted central catheter, or Hickman catheter are permitted
  • Participants who underwent major surgery within 4 weeks before the planned day for the first NKR-2 administration
  • Participants who have received a live vaccine ≤ 6 weeks prior to each NKR 2 administration
  • Participants with uncontrolled intercurrent illness or serious uncontrolled medical disorder including, but not limited to evidence of active pneumonitis on screening chest imaging, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia history (or evidenced after the electrocardiogram planned at screening) and/or pronounced disturbances of the electrical conduction system of the heart, or significant thromboembolic events
  • Participants with significant disorder of coagulation or receiving treatment with warfarin derivatives or heparin
  • Participants who have active infections including, but not limited to viral, bacterial or fungal infections necessitating use of antibiotics/antivirals/antifungal treatment (prophylaxis is acceptable)
  • Participants who are known to be positive or screened positive for hepatitis B (HBsAg positive) or C (anti-HCV positive)
  • Participants who are known to be positive or screened positive for the human immunodeficiency virus (HIV)
  • Participants with a family history of congenital or hereditary immunodeficiency
  • Participants with a history of allergic reactions or hypersensitivity attributed to Human serum albumin or Plasma-lyte A
  • Participant with history of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis and/or active or acute exacerbation of chronic obstructive pulmonary disease
  • Participants on supplemental home oxygen
  • Participants with history of any autoimmune disease Participants with Graves disease and vitiligo will be allowed
  • Participants with a history of a malignancy other than the one evaluated in this study enrollment, with exception of the following circumstances: Participants with a history of malignancy who have been adequately treated and have been disease-free for at least 1 year, and Participants with adequately treated active non-invasive cancers (such as non-melanomatous skin cancer or in-situ bladder, cervical and breast cancers)
  • Participants with psychiatric/social situations or addictive disorders that may compromise the ability of the participants to give informed consent or to comply with the study procedures
  • Female participants who are pregnant or lactating