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

• Status: Not yet recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Treatments: Cyclophosphamide; Fludarabine; Fludarabine phosphate; Melphalan; Mycophenolic Acid; Tacrolimus

Criteria

Inclusion Criteria:

• Patients ages 18 to 65 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. First complete remission with 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 criteria

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, or (viii) Aplastic/hypoplastic marrow with or without detectable persistent disease after induction chemotherapy or after salvage chemotherapy.

b. Patients must be in (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.

Patients cannot be beyond CR3, i.e., have relapsed more than 2 times.

Myelodysplastic syndromes (MDS):

a. De novo MDS with intermediate or high-risk IPSS scores. Patients with intermediate-1 features should have failed to respond to hypomethylating agent therapy, or patients with treatment-related MDS.

Patients must have less than 10% bone marrow blasts

Chronic myeloid leukemia (CML):

1. Failed to achieve cytogenetic remission or have cytogenetic relapse after treatment with at least 2 tyrosine kinase inhibitors, or

2. Accelerated phase or blast phase at any time.

3. 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:

1. Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockroft-Gault formula).

2. Bilirubin equal or less than 1.5 mg/dl except for Gilbert's disease. ALT or AST equal or less than 200 IU/ml for adults. Conjugated (direct) bilirubin less than 2x upper limit of normal.

3. Left ventricular ejection fraction equal or greater than 45%.

4. 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.

Exclusion Criteria:

• HIV positive; active hepatitis B or C.

• Uncontrolled infections; PI is the final arbiter of this criterion.

• Liver cirrhosis.

• 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.

• 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.

• Prior allogeneic SCT

• Other malignancy/cancer diagnosis <2 years ago, not including nonmelanoma skin cancer

• Requiring systemic corticosteroids with prednisone dose >10 mg or equivalent.

• KDS-1001 Donor specific antibodies (dsa) >5000 MFI units

• KDS-1001 Donor anti-C1q positive