A Phase I/II Clinical Trial of Off-the-shelf NK Cell Administration in Combination With Allogeneic SCT to Decrease Disease Relapse in Patients With High-risk Myeloid Malignancies Undergoing Matched Related, Matched Unrelated, One Antigen Mismatched Unrelated, or Haploidentical Stem-cell Transplantation
The goal of this clinical research study is to learn about the safety and effectiveness of giving KDS-1001 in combination with a standard stem cell transplant to patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), or chronic myeloid leukemia (CML). KDS-1001 is a study product created using certain immune cells called natural killer (NK) cells collected from a third-party donor.
⁃ Patients ages 18 to 70 years old at the time of enrollment.
⁃ Patients weighing at least 42 kg
⁃ Patient with the hematologic malignancies described below, as well as an HLA matched related donor, HLA matched unrelated donor, a haploidentical related donor, or a one antigen mismatched unrelated donor. HLA matching includes HLA A, B, C, and DR-B1.
⁃ Patients must have one of the following diseases:
⁃ Acute myeloid leukemia (AML):
⁃ a. With one or more high-risk features defined as: (i) Greater than 1 cycle of induction therapy required to achieve remission; (ii) Preceding myelodysplastic syndrome (MDS);
⁃ Presence of FLT3 mutations or internal tandem duplication or other mutations designated as adverse-risk by the ELN Leukemia Net AML Classification (see Appendix 2):
⁃ t(6;9)(p23;q34.1); DEK-NUP214
⁃ t(v;11q23.3); KMT2A rearranged
⁃ t(9;22)(q34.1;q11.2); BCR-ABL1
⁃ inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1)
• 5 or del(5q); -7; -17/abn(17p)
⁃ Complex karyotype, monosomal karyotype
⁃ Wild-type NPM1 and FLT3-ITDhigh
⁃ Mutated RUNX1
⁃ Mutated ASXL1
⁃ Mutated TP53 (iv) FAB M6 or M7 classification; (v) Adverse cytogenetics: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or complex karyotype [> 3 abnormalities]; or other mutations designated as adverse-risk by the ELN criteria; (vi) Treatment-related AML (vii) Primary induction failure with partial response to therapy who achieve adequate cytoreduction (viii) Aplastic/hypoplastic marrow with or without detectable persistent disease after induction chemotherapy or after salvage chemotherapy.
⁃ (ix) Have minimal residual disease by flow cytometry, FISH, detection of disease related mutations or cytogenetic abnormality after first course of induction chemotherapy (x) Have relapsed after prior allogeneic hematopoietic transplant
⁃ b. Patients must be in one of the following (i) CR: complete remission, (ii) CRi: CR with incomplete hematologic recovery, or (iii) MLFS: morphological leukemia-free state with less than 5% bone marrow blasts.
⁃ (iv) If not in either of the above i-iii, then may be in either of the following:
⁃ Primary induction failure with partial response to therapy who achieve adequate cytoreduction
⁃ Aplastic/hypoplastic marrow with or without detectable persistent disease after induction chemotherapy or after salvage chemotherapy
⁃ Myelodysplastic syndromes (MDS):
⁃ a. De novo MDS with intermediate or high-risk IPSS scores, chronic myelomonocytic leukemia (CMML) or treatment-related MDS. Patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy. .
⁃ Patients must have less than 10% bone marrow blasts
⁃ Chronic myeloid leukemia (CML):
⁃ Failed to achieve cytogenetic remission or have cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or
⁃ Accelerated phase or blast phase at any time, or
⁃ Intolerant of available TKIs
⁃ Performance score of at least 70% by Karnofsky or 0 to 1 by ECOG.
⁃ Adequate major non-hematopoietic organ system function as demonstrated by:
⁃ Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockcroft-Gault formula).
⁃ Bilirubin equal or less than 1.5 mg/dL except for Gilbert's disease. ALT or AST equal or less than 200 U/L for adults. Conjugated (direct) bilirubin less than 2x upper limit of normal.
⁃ Left ventricular ejection fraction equal or greater than 45%.
⁃ Diffusing capacity for carbon monoxide (DLCO) equal or greater than 60% predicted corrected for hemoglobin.
⁃ Ability to understand and willingness to sign the written informed consent document.
⁃ Sexually active males and females of childbearing potential must agree to use a form of contraception considered effective and medically acceptable by the Investigator while on study.