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

February 15, 2024 updated by: M.D. Anderson Cancer Center

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Study Type

Interventional

Enrollment (Estimated)

24

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Drug: Cyclophosphamide
Given by IV
Experimental: 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.
Drug: Mesna
Given by IV
Experimental: Filgrastim
Starting on Day 7, you will begin to receive filgrastim as an injection under the skin 1 time a day.
Drug: Filgrastim
Given by IV
Experimental: Melphalan
On Day -7, you will receive melphalan by vein over about 30 minutes.
Drug: Melphalan
Given by IV
Experimental: Fludarabine phosphate
On Days -7, -6, -5, and -4, you will receive fludarabine by vein about 1 hour.
Drug: Fludarabine phosphate
Given by IV
Experimental: 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.
Drug: Tacrolimus
Given by IV
Experimental: Mycophenolate mofetil
by mouth 3 times a day for 90 days or longer.
Drug: Mycophenolate mofetil
Given by IV
Experimental: Total Body Irradiation One Dose
on Day -2, you may receive 1 dose of total body irradiation (TBI).
Drug: Total Body Irradiation One Dose
Given by IV

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of participants with Adverse Event Failure
Time Frame: 100 days post-transplant
100 days post-transplant

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

M.D. Anderson Cancer Center

Investigators

  • Principal Investigator: Jeremy Ramdial, MD, M.D. Anderson Cancer Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

April 8, 2022

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

October 11, 2021

First Submitted That Met QC Criteria

November 1, 2021

First Posted (Actual)

November 10, 2021

Study Record Updates

Last Update Posted (Actual)

February 16, 2024

Last Update Submitted That Met QC Criteria

February 15, 2024

Last Verified

February 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2021-0329
  • NCI-2021-12094 (Other Identifier: NCI-CTRP Clinical Trials Reporting Registry)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Acute Myeloid Leukemia

Clinical Trials on Cyclophosphamide

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Benin

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe