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

Phase 1

Recruiting

• Conditions: Myeloid Malignancies; Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myeloid Leukemia

• Registration Number: NCT05115630
• Lead Sponsor: M.D. Anderson Cancer Center

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-10-11
• Last Update Posted: 2 September 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Inclusion Criteria:<br><br> 1. Patients ages 18 to 70 years old at the time of enrollment.<br><br> 2. Patients weighing at least 42 kg<br><br> 3. Patient with the hematologic malignancies described below, as well as an HLA matched<br> related donor, HLA matched unrelated donor, a haploidentical related donor, or a one<br> antigen mismatched unrelated donor. HLA matching includes HLA A, B, C, and DR-B1.<br><br> 4. Patients must have one of the following diseases:<br><br> Acute myeloid leukemia (AML):<br><br> a. With one or more high-risk features defined as: (i) Greater than 1 cycle of<br> induction therapy required to achieve remission; (ii) Preceding myelodysplastic<br> syndrome (MDS);<br><br> Presence of FLT3 mutations or internal tandem duplication or other mutations<br> designated as adverse-risk by the ELN Leukemia Net AML Classification (see Appendix<br> 2):<br><br> Adverse:<br><br> - t(6;9)(p23;q34.1); DEK-NUP214<br><br> - t(v;11q23.3); KMT2A rearranged<br><br> - t(9;22)(q34.1;q11.2); BCR-ABL1<br><br> - inv(3)(q21.3q26.2) or t(3;3)(q21.3;q26.2); GATA2,MECOM(EVI1)<br><br> - -5 or del(5q); -7; -17/abn(17p)<br><br> - Complex karyotype, monosomal karyotype<br><br> - Wild-type NPM1 and FLT3-ITDhigh<br><br> - Mutated RUNX1<br><br> - Mutated ASXL1<br><br> - Mutated TP53 (iv) FAB M6 or M7 classification; (v) Adverse cytogenetics: -5,<br> del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8 or<br> complex karyotype [> 3 abnormalities]; or other mutations designated as<br> adverse-risk by the ELN criteria; (vi) Treatment-related AML (vii) Primary<br> induction failure with partial response to therapy who achieve adequate<br> cytoreduction (viii) Aplastic/hypoplastic marrow with or without detectable<br> persistent disease after induction chemotherapy or after salvage chemotherapy.<br><br> (ix) Have minimal residual disease by flow cytometry, FISH, detection of disease<br> related mutations or cytogenetic abnormality after first course of induction<br> chemotherapy (x) Have relapsed after prior allogeneic hematopoietic transplant<br><br> AND<br><br> b. Patients must be in one of the following (i) CR: complete remission, (ii) CRi: CR<br> with incomplete hematologic recovery, or (iii) MLFS: morphological leukemia-free<br> state with less than 5% bone marrow blasts.<br><br> (iv) If not in either of the above i-iii, then may be in either of the following:<br><br> 1. Primary induction failure with partial response to therapy who achieve adequate<br> cytoreduction<br><br> 2. Aplastic/hypoplastic marrow with or without detectable persistent disease after<br> induction chemotherapy or after salvage chemotherapy<br><br> Myelodysplastic syndromes (MDS):<br><br> a. De novo MDS with intermediate or high-risk IPSS scores, chronic myelomonocytic<br> leukemia (CMML) or treatment-related MDS. Patients with intermediate-1 features<br> should have failed to respond to hypomethylating agent therapy. .<br><br> Patients must have less than 10% bone marrow blasts<br><br> Chronic myeloid leukemia (CML):<br><br> 1. Failed to achieve cytogenetic remission or have cytogenetic relapse after<br> treatment with at least 2 tyrosine kinase inhibitors, or<br><br> 2. Accelerated phase or blast phase at any time, or<br><br> 3. Intolerant of available TKIs<br><br> 5. Performance score of at least 70% by Karnofsky or 0 to 1 by ECOG.<br><br> 6. Adequate major non-hematopoietic organ system function as demonstrated by:<br><br> 1. Serum creatinine clearance equal or more than 50 ml/min (calculated with<br> Cockcroft-Gault formula).<br><br> 2. Bilirubin equal or less than 1.5 mg/dL except for Gilbert's disease. ALT or AST<br> equal or less than 200 U/L for adults. Conjugated (direct) bilirubin less than<br> 2x upper limit of normal.<br><br> 3. Left ventricular ejection fraction equal or greater than 45%.<br><br> 4. Diffusing capacity for carbon monoxide (DLCO) equal or greater than 60%<br> predicted corrected for hemoglobin.<br><br> 7. Ability to understand and willingness to sign the written informed consent document.<br><br> 8. Sexually active males and females of childbearing potential must agree to use a form<br> of contraception considered effective and medically acceptable by the Investigator<br> while on study.<br><br>Exclusion criteria:<br><br> 1. HIV positive; active hepatitis B or C.<br><br> 2. Uncontrolled infections; PI is the final arbiter of this criterion.<br><br> 3. Liver cirrhosis.<br><br> 4. CNS involvement within 3 months prior to the transplant.<br><br> 5. Positive pregnancy test in a woman with child bearing potential defined as not<br> post-menopausal for 12 months or no previous surgical sterilization.<br><br> 6. Inability to comply with medical therapy or follow-up.<br><br> 7. Patient with a known history of allergic reactions to any constituents of the<br> product, including a known history of allergic reactions to cellular products or<br> DMSO.<br><br> 8. Other malignancy/cancer diagnosis with active disease or in remission and <2 years<br> ago, not including nonmelanoma skin cancer<br><br> 9. Requiring systemic corticosteroids with prednisone dose >10 mg or equivalent.<br><br> 10. KDS-1001 Donor specific antibodies (dsa) >3000 MFI units or C1q positive

Exclusion Criteria

Not provided

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Number of participants with Adverse Event Failure