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

NCT ID: NCT05115630

Last Updated: 2025-12-19

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-04-08

Study Completion Date

2025-05-15

Brief Summary

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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.

Detailed Description

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Primary Objective

Assess the safety and effectiveness of "off the shelf" third party NK cells in combination with allogeneic SCT in patients with myeloid malignancies.

Secondary Objectives

To assess NK cell related toxicities To estimate the proportion of patients with engraftment/graft failure. To assess the rate of leukemia relapse, disease-free survival (DFS), overall survival (OS), and GVHD-free, Relapse-free survival (GRFS) after transplantation by one year.

To estimate the non-relapse mortality (NRM) at day 100, day 180 and 1 year post-transplant.

To estimate the cumulative incidence of grade 2-4 and grades 3-4 aGVHD at day 100. To assess the rate of chronic GVHD within the first-year post transplantation. To assess rate of BK, CMV, and Adenovirus infections. To assess MRD. To assess immune reconstitution post-transplant

Conditions

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Myeloid Malignancies Acute Myeloid Leukemia Myelodysplastic Syndrome Chronic Myeloid Leukemia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Melphalan

On Day -7, you will receive melphalan by vein over about 30 minutes.

Group Type EXPERIMENTAL

Melphalan

Intervention Type DRUG

Given by IV

Fludarabine phosphate

On Days -7, -6, -5, and -4, you will receive fludarabine by vein about 1 hour.

Group Type EXPERIMENTAL

Fludarabine phosphate

Intervention Type DRUG

Given by IV

Tacrolimus

Starting on Day 5, you will begin receiving tacrolimus to help lower the risk of GVHD. You will begin by receiving it nonstop by vein until you are able to take it by mouth. You will then take tacrolimus by mouth 2 times a day for about 3 months.

Group Type EXPERIMENTAL

Tacrolimus

Intervention Type DRUG

Given by IV

Mycophenolate mofetil

by mouth 3 times a day for 90 days or longer.

Group Type EXPERIMENTAL

Mycophenolate mofetil

Intervention Type DRUG

Given by IV

Total Body Irradiation One Dose

on Day -2, you may receive 1 dose of total body irradiation (TBI).

Group Type EXPERIMENTAL

Total Body Irradiation One Dose

Intervention Type DRUG

Given by IV

Cyclophosphamide

On Days 3 and 4, you will receive cyclophosphamide by vein over about 3 hours to help lower the risk of graft-versus-host disease

Group Type EXPERIMENTAL

Cyclophosphamide

Intervention Type DRUG

Given by IV

Mesna

On Days 3 and 4, You will also receive mesna by vein over 30 minutes every 4 hours for a total of 10 mesna doses.

Group Type EXPERIMENTAL

Mesna

Intervention Type DRUG

Given by IV

Filgrastim

Starting on Day 7, you will begin to receive filgrastim as an injection under the skin 1 time a day.

Group Type EXPERIMENTAL

Filgrastim

Intervention Type DRUG

Given by IV

Interventions

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Cyclophosphamide

Given by IV

Intervention Type DRUG

Mesna

Given by IV

Intervention Type DRUG

Filgrastim

Given by IV

Intervention Type DRUG

Melphalan

Given by IV

Intervention Type DRUG

Fludarabine phosphate

Given by IV

Intervention Type DRUG

Tacrolimus

Given by IV

Intervention Type DRUG

Mycophenolate mofetil

Given by IV

Intervention Type DRUG

Total Body Irradiation One Dose

Given by IV

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients ages 18 to 70 years old at the time of enrollment.
2. Patients weighing at least 42 kg
3. 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.
4. 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):

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

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:
1. Primary induction failure with partial response to therapy who achieve adequate cytoreduction
2. 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):
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, or
3. Intolerant of available TKIs
5. Performance score of at least 70% by Karnofsky or 0 to 1 by ECOG.
6. Adequate major non-hematopoietic organ system function as demonstrated by:

1. Serum creatinine clearance equal or more than 50 ml/min (calculated with Cockcroft-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 U/L 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.
7. Ability to understand and willingness to sign the written informed consent document.
8. 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

1. HIV positive; active hepatitis B or C.
2. Uncontrolled infections; PI is the final arbiter of this criterion.
3. Liver cirrhosis.
4. CNS involvement within 3 months prior to the transplant.
5. Positive pregnancy test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization.
6. Inability to comply with medical therapy or follow-up.
7. 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.
8. Other malignancy/cancer diagnosis with active disease or in remission and \<2 years ago, not including nonmelanoma skin cancer
9. Requiring systemic corticosteroids with prednisone dose \>10 mg or equivalent.
10. KDS-1001 Donor specific antibodies (dsa) \>3000 MFI units or C1q positive
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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M.D. Anderson Cancer Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jeremy Ramdial, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

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M D Anderson Caner Center

Houston, Texas, United States

Site Status

Countries

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United States

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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http://www.mdanderson.org

MD Anderson Cancer Center

Other Identifiers

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NCI-2021-12094

Identifier Type: OTHER

Identifier Source: secondary_id

2021-0329

Identifier Type: -

Identifier Source: org_study_id