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Refractory Acute Myeloid LeukemiaPhase 2NCT04354025

Cytokine-induced Memory-like NK Cells in Combination With Chemotherapy in Pediatric Patents With Refractory or Relapsed AML

A Phase 2 study testing Cytokine induced memory-like NK cells, Fludarabine and Ara-C in people with Refractory Acute Myeloid Leukemia and Relapsed 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Withdrawn

Withdrawn.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

This phase 2 clinical trial investigates the effectiveness of cytokine-induced memory-like natural killer (CIML NK) cells in combination with FLAG chemotherapy as a treatment for refractory or relapsed AML. Read more about this study

Who is it for?
Ages 1 year to 21 years
What is being tested?
Cytokine induced memory-like NK cells, Fludarabine and Ara-C
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 2023to 31 Jul 2028
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 1 year to 21 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • Refractory AML without complete remission (CR) after induction therapy (primary induction failure) or relapsed AML after obtaining a CR. Disease defined by one of the following:
  • ≥ 5% blasts in the bone marrow (M2/M3 bone marrow), with or without extramedullary disease
  • absolute blast count greater than 1,000 per microliter in the peripheral blood with or without extramedullary disease.
  • Age requirement for pediatric cohort: 1-21 years of age.
  • Available HLA-haploidentical donor that meets the following criteria:
  • Related donor (parent, sibling, offspring, or offspring of sibling)
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  • At least 18 years of age
  • HLA-haploidentical donor/recipient match by at least Class I serologic typing at the A\&B locus.
  • In general, good health and medically able to tolerate leukapheresis required for harvesting the NK cells for this study.
  • Negative for hepatitis, HTLV, and HIV on donor viral screen
  • Not pregnant
  • Voluntary written consent to participate in this study
  • 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 upper limit of normal (ULN)
  • Creatinine within normal institutional limits OR creatinine clearance > 50 mL/min/1.73 m2 by Schwartz formula or GFR (See Appendix B)
  • 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 infusion of the CIML NK cells. 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 throughout the DLT evaluation period.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • Relapsed after allogeneic transplantation.
  • Isolated extramedullary relapse
  • Circulating blast count >30,000/µL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed).
  • Patients with any of the following diagnoses:
  • Down's syndrome
  • Acute promyelocytic leukemia (APL)
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  • Juvenile myelomonocytic leukemia (JMML)
  • Uncontrolled bacterial or viral infections, or known HIV, Hepatitis B or C infection.
  • Known hypersensitivity to one or more of the study agents.
  • Received any investigational drugs within the 14 days prior to the first dose of fludarabine.
  • Pregnant

About this study

Official title: A Phase 2 Study of Cytokine-induced Memory-like NK Cells in Combination With Chemotherapy in Pediatric Patients With Refractory or Relapsed AML

This phase 2 clinical trial investigates the effectiveness of cytokine-induced memory-like natural killer (CIML NK) cells in combination with FLAG chemotherapy as a treatment for refractory or relapsed AML. Previous studies in adults with AML sowed successful induction of remission and a previous phase 1 study demonstrated that CIML NK cells can be used safely in pediatric patients. This phase 2 study uses FLAG chemotherapy to lower leukemic burden and suppress the recipient's immune system to provide an optimal environment for CIML NK cell expansion and anti-leukemic activity.

Being tested
Cytokine induced memory-like NK cells, Fludarabine, Ara-C, G-CSF, Interleukin-2
Medical subject headings
Leukemia, Myeloid, Acute

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

    Also called CIML NK cells

    -The CIML NK cells (maximum dose capped at 10 x 106/kg, minimum dose allowed is 0.5 x 106/kg) will be infused on Day 0 without a filter or pump.

  • FludarabineDrug

    -Fludarabine (dose: 30 mg/m^2 per dose) will be given daily beginning on Day -7 for a total of 5 doses administered as an IV infusion over 30 minutes.

  • Ara-CDrug

    Also called Cytarabine

    -Ara-C (dose: 2000mg/m^2 per dose) will be given daily for a total of 5 doses administered as IV infusion over 3 hours, starting the same day as fludarabine.

  • G-CSFDrug

    Also called Filgrastim

    -Filgrastim (dose: 5 mcg/kg per dose to a maximum of 300 mcg) will be given subcutaneously daily for a total of 5 doses starting the same day as fludarabine and ara-C.

  • Interleukin-2Drug

    Also called IL-2

    -IL-2 will be administered subcutaneously at a dose of 1 million units/m2 every other day from Day 0 to Day +12 (7 doses total).

  • LeukapheresisProcedure or surgery

    -Donor only

Study groups in NCT04354025
Study groupRoleWhat they receive
Recipient: FLAG + CIML NK Cells + IL-2Experimental-The recipient will begin a chemotherapy regimen of fludarabine, cytarabine and GCSF starting on Day -7. The haploidentical donor identified by HLA matching of the immediate family members will undergo non-mobilized large volume (20 L) leukapheresis on Day -1, and the NK cell product will be infused into the recipient on Day 0. CIML NK cells will be infused at maximum cell dose of 10 x 106/kg. Subcutaneous IL-2 will begin approximately 2-4 hours after infusion and will continue every other day through Day 12 for a total of 7 doses.
Receives: Biological: Cytokine induced memory-like NK cells; Drug: Fludarabine; Drug: Ara-C; Drug: G-CSF; Drug: Interleukin-2
Donor:Other-On Day -1 (one day before the planned NK cell infusion), peripheral blood mononuclear cells will be collected by a single standard apheresis over 4-5 hours (with a target volume of at least 20 L) from the identified haploidentical donor. The apheresis procedure will be done as per standard institutional procedures (which may include placement of a central line if necessary). If the goal minimum NK cell dose will not be met based on the initial assessment of the leukapheresis product, a second collection/procedure may be performed.
Receives: Procedure: Leukapheresis

What is being measured

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

  1. Response rate (complete remission (CR) plus complete remission with incomplete blood count recovery (CRi))

    • Complete remission (CR) requires all of the following:
    • Bone marrow:
    • Morphologically leukemia free state (≤ 5% myeloblasts) with normal maturation of all cell lines. Persistent dysplasia may be noted
    • Peripheral blood:
    • Platelets ≥ 100,000/uL
    • Neutrophils ≥ 1000/uL
    • Complete remission with incomplete blood count recovery (CRi):
    • All of the above criteria for CR must be met, except that absolute neutrophils <1000/μL or platelets <100,000 /μL in the blood.

    Measured: Day 28

  2. Percentage of patients able to proceed to stem cell transplant

    Measured: Up to 60 days

Secondary outcomes (6)

  1. Disease-free survival (DFS)

    -DFS is defined as the time from the day CR or CRi is documented until disease progression or death.

    Measured: Up to 2 years

  2. Overall survival (OS)

    -OS is defined from the date of first dose of fludarabine on this study until death.

    Measured: Up to 2 years

  3. Percentage of patients who achieve minimum residual disease (MRD)-negative status

    Measured: Day 28

  4. Safety of regimen as measured by number of adverse events

    -Adverse events will be collected from Day 0 to Day 35; however, bone marrow suppression (ANC ≤ 500/mcL) and adverse events of GVHD involving the liver, skin, or gastrointestinal tract will be recorded to Day 100

    Measured: From Day 0 to Day 100

  5. Duration of remission

    Measured: Up to 2 years

  6. Time to progression

    Measured: Up to 2 years

Timeline

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

  1. First posted21 Apr 2020
  2. Study start30 Jun 2023 (estimated)
  3. Primary completion30 Sep 2026 (estimated)
  4. Study completion31 Jul 2028 (estimated)

Why it stopped: Principal investigator decided not to move forward with the study.

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
Parallel groups
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04354025
Sponsor's protocol ID
20-x130
Status last verified
Mar 2023
First submitted
16 Apr 2020
Last updated
4 Apr 2023
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 Ara-C in people with Refractory Acute Myeloid Leukemia and Relapsed 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 23 inclusion and 11 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 4 Apr 2023. 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?

Response rate (complete remission (CR) plus complete remission with incomplete blood count recovery (CRi)) (time frame: Day 28). The study lists 2 primary outcomes in all. 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 NCT04354025.

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 4 Apr 2023.

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