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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05115630
Recruitment Status : Recruiting
First Posted : November 10, 2021
Last Update Posted : November 22, 2022
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Description
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Brief 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.

Condition or disease Intervention/treatment Phase
Myeloid Malignancies Acute Myeloid Leukemia Myelodysplastic Syndrome Chronic Myeloid Leukemia Drug: Cyclophosphamide Drug: Mesna Drug: Filgrastim Drug: Melphalan Drug: Fludarabine phosphate Drug: Tacrolimus Drug: Mycophenolate mofetil Drug: Total Body Irradiation One Dose Phase 1 Phase 2

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 24 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : April 8, 2022
Estimated Primary Completion Date : June 1, 2024
Estimated Study Completion Date : June 1, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
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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


Outcome Measures
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Primary Outcome Measures :
  1. Number of participants with Adverse Event Failure [ Time Frame: 100 days post-transplant ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05115630


Contacts
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Contact: Jeremy Ramdial, MD (713) 745-0146 jlramdial@mdanderson.org

Locations
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United States, Texas
M D Anderson Caner Center Recruiting
Houston, Texas, United States, 77030
Contact: Jeremy Ramdial, MD    713-745-0146    jlramdial@mdanderson.org   
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Jeremy Ramdial, MD M.D. Anderson Cancer Center
More Information
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Additional Information:

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT05115630    
Other Study ID Numbers: 2021-0329
NCI-2021-12094 ( Other Identifier: NCI-CTRP Clinical Trials Reporting Registry )
First Posted: November 10, 2021    Key Record Dates
Last Update Posted: November 22, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Leukemia
Leukemia, Myeloid
Neoplasms
Leukemia, Myelogenous, Chronic, BCR-ABL Positive
Myelodysplastic Syndromes
Neoplasms by Histologic Type
Bone Marrow Diseases
Hematologic Diseases
Myeloproliferative Disorders
Mycophenolic Acid
Cyclophosphamide
Melphalan
Fludarabine
Fludarabine phosphate
Tacrolimus
 Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antimetabolites, Antineoplastic
Antimetabolites
Calcineurin Inhibitors
Enzyme Inhibitors
Antibiotics, Antineoplastic
Antibiotics, Antitubercular