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Relapsed Acute Myeloid LeukemiaPhase 2NCT04893915

Cytokine-induced Memory-like NK Cells in Relapsed/Refractory AML and MDS

A Phase 2 study testing Cytokine-induced memory-like NK cells, Fludarabine and Cyclophosphamide in people with Relapsed Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will receive lymphodepleting chemotherapy (Flu/Cy) and two infusions of cytokine-induced memory-like NK cells at the previously defined maximum tolerated dose (MTD), fourteen days apart. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Cytokine-induced memory-like NK cells, Fludarabine and Cyclophosphamide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
30 Jun 2022to 31 Dec 2024
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Refractory AML without CR after induction therapy (primary induction failure); relapsed AML after obtaining a CR; progressive AML after non-intensive therapy (e.g., HMA + venetoclax or targeted therapy); Intermediate risk to very-high-risk MDS by IPSS-R that is relapsed or refractory after prior therapy with an HMA-containing regimen
  • At least 18 years of age.
  • Available allogeneic donor that meets the following criteria:
  • Able and willing to undergo multiple rounds of leukapheresis
  • At least 18 years of age
  • In general good health, and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
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  • Negative for hepatitis, HTLV, and HIV on donor viral screen
  • Not pregnant
  • Voluntary written consent to participate in this study
  • All HLA-match/mismatch statuses will be included, with preference for unmatched donors all else being equal
  • Patients with known CNS involvement with AML are eligible provided that they have been treated and CSF is clear for at least 2 weeks prior to enrollment into the study. CNS therapy (chemotherapy or radiation) should continue as medically indicated during the study treatment.
  • Karnofsky/Lansky performance status > 50 %
  • Adequate organ function as defined below:
  • Total bilirubin < 2 mg/dL
  • AST(SGOT)/ALT(SGPT) < 3.0 x ULN
  • Creatinine within normal institutional limits OR creatinine clearance ≥ 40 mL/min by Cockcroft-Gault Formula
  • Oxygen saturation ≥90% on room air
  • Ejection fraction ≥35%
  • Able to be off corticosteroids and any other immune suppressive medications beginning on Day -3 and continuing until 30 days after the last infusion of the NK cell product. However, use of low-level corticosteroids is permitted if deemed medically necessary. Low-level corticosteroid use is defined as 10mg or less of prednisone (or equivalent for other steroids) per day.
  • Women of childbearing potential must have a negative pregnancy test within 28 days prior to study registration. Female and male patients (along with their female partners) must agree to use two forms of acceptable contraception, including one barrier method, during participation in the study and until 30 days after the last NK cell product infusion.
  • Ability to understand and willingness to sign an IRB approved written informed consent document

Who cannot join

  • Relapsed after allogeneic transplantation.
  • Circulating blast count >30,000/µL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed).
  • Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
  • Uncontrolled angina, severe uncontrolled ventricular arrhythmias, or EKG suggestive of acute ischemia or active conduction system abnormalities.
  • New progressive pulmonary infiltrates on screening chest x-ray or chest CT scan that have not been evaluated with bronchoscopy. Infiltrates attributed to infection must be stable/ improving after 1 week of appropriate therapy (4 weeks for presumed or proven fungal infections).
  • Known hypersensitivity to one or more of the study agents.
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  • Received any investigational drugs within the 14 days prior to the first dose of fludarabine.
  • Pregnant and/or breastfeeding.
  • Any condition that, in the opinion of the investigator, would prevent the participant from consenting to or participating in the study

About this study

Official title: A Phase 2 Study of Cytokine-induced Memory-like NK Cells in Relapsed/Refractory AML and MDS

Patients with relapsed/refractory acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) will receive lymphodepleting chemotherapy (Flu/Cy) and two infusions of cytokine-induced memory-like NK cells at the previously defined maximum tolerated dose (MTD), fourteen days apart. Low dose rhIL-2 will be administered to patients for in vivo expansion following cell infusion. Patients will be assessed for anti-leukemic efficacy and safety. Re-infusion of patients who relapsed after clinical response will be considered.

Being tested
Cytokine-induced memory-like NK cells, Fludarabine, Cyclophosphamide, Donor Leukapheresis, Interleukin-2
Medical subject headings
Leukemia, Myeloid, Acute, Myelodysplastic Syndromes

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cytokine-induced memory-like NK cellsBiological

    Cell product processing is performed at the Siteman Cancer Center Biological Therapy Core or another FACT-accredited cellular therapy production facility that can manufacture the product per the IND CMC.

  • FludarabineDrug

    -Lymphodepleting regimen

  • CyclophosphamideDrug

    -Lymphodepleting regimen

  • Donor LeukapheresisProcedure or surgery

    -Apheresis will be performed via peripheral IVs or central line, as determined by the apheresis team.

  • Interleukin-2Drug

    Also called IL-2

    -IL-2 will start approximately 2-4 hours after the NK cell infusions.

Study groups in NCT04893915
Study groupRoleWhat they receive
Lead In Cohort Recipient: Cytokine-induced memory-like NK cellsExperimental* Fludarabine and cyclophosphamide beginning on Day -6. * NK cell product will be infused on Day 0. * IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses. * NK cell product will be infused into the recipient on Day +14. * IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 26 for an additional 7 doses, and a total of 14 doses, to a maximum of two vials of rhIL-2 per IL-2 course. * In the Lead-in Cohort, three patients will receive NK cell product on Day 0 and Day +14, receiving the maximum NK cells generated, capped at 20x10^6/kg. * Patients that have an initial response but then subsequently relapse or progress will be able to receive a third dose of NK cell product with or without lymphodepleting chemotherapy depending on the interval duration between the second dose and relapse, after approval by the study PI. The third dose should be administered not less than 45 days from Day 0.
Receives: Biological: Cytokine-induced memory-like NK cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Interleukin-2
Phase II Recipient: Cytokine-induced memory-like NK cellsExperimental* Fludarabine and cyclophosphamide beginning on Day -6. * NK cell product will be infused on Day 0. * IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses. * NK cell product will be infused into the recipient on Day +14. * IL-2 will begin 2-4 hours after infusion and will continue every other day through Day 26 for an additional 7 doses, and a total of 14 doses, to a maximum of two vials of rhIL-2 per IL-2 course. * Will receive the NK cell product on Day 0 and Day +14, receiving the maximum NK cells generated, capped at 20x10^6/kg. * Patients that have an initial response but then subsequently relapse or progress will be able to receive a third dose of NK cell product with or without lymphodepleting chemotherapy depending on the interval duration between the second dose and relapse, after approval by the study PI. The third dose should be administered not less than 45 days from Day 0.
Receives: Biological: Cytokine-induced memory-like NK cells; Drug: Fludarabine; Drug: Cyclophosphamide; Drug: Interleukin-2
DonorExperimental* The allogeneic donor will undergo non-mobilized large volume (20-L) leukapheresis on Day -1. * On Day +13 the allogeneic donor will again undergo non-mobilized large volume (20-L) leukapheresis
Receives: Procedure: Donor Leukapheresis

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Overall response rate (ORR) of recipients

    • Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete blood count recovery (CRi).
    • Response will be assessed according to the criteria from the International Working Group Response Criteria

    Measured: Through 12 month follow-up

Secondary outcomes (13)

  1. Overall survival (OS) of recipients

    -Defined as time from first dose of lymphodepleting chemotherapy (LDC) until death from any cause

    Measured: Through completion of follow-up (estimated to be 12 months)

  2. Event free survival (EFS) of recipients

    -Defined as time from first dose of lymphodepleting chemotherapy (LDC) until treatment failure, relapse from complete response, or death

    Measured: Through completion of follow-up (estimated to be 12 months)

  3. Duration of overall response (DOR) of recipients

    -Defined as duration for first occurrence of documented ORR until disease progression or death

    Measured: Through 12 month follow-up

  4. Duration of complete response (DoCR) of recipients

    -Defined as duration from documented complete remission until disease progression or death

    Measured: Through 12 month follow-up

  5. Proportion of recipients that receive multiple doses of NK cell product

    Measured: Through Day +14 of all recipients enrolled (estimated to be 19 months)

  6. Number of dose-limiting toxicities (DLTs) that recipients experience in the safety lead-in cohort

    Measured: Through Day 28

  7. Mortality rate of recipients

    Measured: Day +30

  8. Mortality rate of recipients

    Measured: Day +100

  9. Number of adverse events experienced by recipients

    • Incidence, nature, and severity of adverse events
    • Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC < 500/µL) and adverse events of graft-versus-host disease (GVHD) involving the liver, skin, or gastrointestinal tract will be recorded until Day +100.

    Measured: Through Day +100

  10. Proportion of recipients with prolonged cytopenia

    Measured: At 8 weeks

  11. Change in quality of life experienced by recipients as measured by the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (EORTC QLQ-C30)

    Measured: Day 0, Day +28, Day +100, 6 months, 9 months, and 12 months

  12. Overall response rate (ORR) of recipients compared across subgroups

    • Subgroups will be defined by degree of HLA-match from allogeneic donor
    • Defined as the proportion of patients achieving complete remission (CR), complete remission with partial hematologic recovery (CRh), and complete remission with incomplete blood count recovery (CRi).
    • Response will be assessed according to the criteria from the International Working Group Response Criteria

    Measured: Through 12 month follow-up

  13. Number of adverse events experienced by recipients compared across subgroups

    • Subgroups will be defined by degree of HLA-match from allogeneic donor
    • Incidence, nature, and severity of adverse events
    • Adverse events will be collected from Day 0 to Day +35; however, bone marrow suppression (ANC < 500/µL) and adverse events of graft-versus-host disease (GVHD) involving the liver, skin, or gastrointestinal tract will be recorded until Day +100.

    Measured: Through Day +100

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted20 May 2021
  2. Study start30 Jun 2022 (estimated)
  3. Primary completion31 Dec 2024 (estimated)
  4. Study completion31 Dec 2024 (estimated)

Why it stopped: No funding support

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04893915
Sponsor's protocol ID
202106075
Status last verified
Feb 2022
First submitted
14 May 2021
Last updated
11 Mar 2022
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Cytokine-induced memory-like NK cells, Fludarabine and Cyclophosphamide in people with Relapsed Acute Myeloid Leukemia and Refractory Acute Myeloid Leukemia, run by Washington University School of Medicine.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 21 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 11 Mar 2022. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Overall response rate (ORR) of recipients (time frame: Through 12 month follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04893915.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2022.

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