Off-the-shelf NK Cells + SCT for Myeloid Malignancies

Korábbi kezelés

• CNS involvement within 3 months prior to the transplant.
• Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
• Inability to comply with medical therapy or follow-up.
• Requiring systemic corticosteroids with prednisone dose >10 mg or equivalent.
• KDS-1001 Donor specific antibodies (dsa) >3000 MFI units or C1q positive

Más betegség

• HIV positive; active hepatitis B or C.
• Uncontrolled infections; PI is the final arbiter of this criterion.
• Patient with a known history of allergic reactions to any constituents of the product, including a known history of allergic reactions to cellular products or DMSO.

Életkor

• Other malignancy/cancer diagnosis with active disease or in remission and <2 years ago, not including nonmelanoma skin cancer

Egyéb

• Liver cirrhosis.

• 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):
  • 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):
  • Adverse:
  • 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
  • AND
  • 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):
  • 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.