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Acute Myeloid Leukemia (AML)Phase 2NCT04395092

Haplo-identical Natural Killer (NK) Cells to Prevent Post-Transplant Relapse in AML and MDS (NK-REALM)

A Phase 2 study testing K-NK002, Conditioning Regimen and HaploBMT in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS), run by Kiadis Pharma at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

This study is a Phase II, single arm, open label multicenter trial designed to investigate the use of haploidentical donor derived NK cells (K-NK002) for the treatment of patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who are undergoing haploidentical donor bone marrow… Read more about this study

Who is it for?
Ages 18 to 65 years
What is being tested?
K-NK002, Conditioning Regimen and HaploBMT
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
13 Nov 2020to Nov 2023
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 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 to 65 years.
  • Weight at least 45 kg.
  • Patients with AML must have high risk for disease relapse AND be in complete remission (CR), complete remission with incomplete hematologic recovery (CRi) or morphologic leukemia free state (MLFS). Patients with FLT3 internal tandem duplication (FLT3/ITD) mutation are eligible but must be made aware of alternative treatments available, e.g. tyrosine kinase inhibitor therapy as maintenance following transplantation.
  • AML patients must be in CR, CRi or a MLFS, as defined by ELN 2017.
  • Patients with high-risk MDS must meet one of the following criteria:
  • i. De novo MDS with intermediate/high/very high Revised International Prognostic Scoring System (R-IPSS) risk scores with
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  • Bone marrow blasts < 10%, AND
  • Patients may be treatment-naïve, or have received prior treatment with hypomethylating agents or other therapies.
  • ii. Secondary/therapy-related MDS with bone marrow blasts < 10%.
  • Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI) of 3 or less. The presence of prior malignancy will not be used to calculated HCT-CI for this trial to allow for the inclusion of patients with secondary or therapy-related AML or MDS.
  • Cardiac function: LVEF ≥ 45%.
  • Pulmonary function: DLCO corrected for hemoglobin ≥ 60% and FEV1 ≥ to 60% the predicted value.
  • Serum creatinine < 1.5 mg/dL or creatinine clearance by Cockroft-Gault ≥ to 50 ml/min
  • Hepatic ALT/AST < 5 x the institutional upper limit of normal (ULN) and total bilirubin < 1.5 mg/dl with conjugated (direct) bilirubin < 2 x ULN.
  • Indirect hyperbilirubinemia due to Gilbert's syndrome is allowed including total bilirubin ≥ to 1.5 mg/dl
  • Karnofsky Performance Score ≥ to 70%.
  • Available first-degree related mismatched bone marrow donor [biologic parent, siblings (full or half) or children] as follows:
  • Donor must be at least a full haplotype match (3/6 or 4/6 match only; 5/6 matches are not allowed) for human leukocyte antigen (HLA)-A and -B at intermediate (or higher) resolution, and -DRB1 at high resolution using DNA-based typing, AND
  • Donor must be willing to donate bone marrow, AND
  • Donor should be a candidate for bone marrow harvest, according to institutional standards.
  • Female patients must either:
  • Be of non-childbearing potential, either postmenopausal or surgically sterilized.
  • Or, if of childbearing potential agree to practice two effective methods of contraception or agree to completely abstain for intercourse from the time of signing the informed consent form through receiving immunosuppressive therapy post-transplant.
  • Male patients (even if surgically sterilized), and their female partners of childbearing potential must agree to use a highly effective contraception method.
  • Voluntary written consent obtained prior to the performance of any study-related procedure.

Who cannot join

  • Prior allogeneic transplant.
  • AML beyond CR2.
  • Patients who have a suitable HLA-matched related donor.
  • Donor specific anti-HLA antibodies (DSA) greater than 1000 MFI.
  • Hepatitis B, Hepatitis C, or HIV positive by PCR.
  • Liver cirrhosis or portal hypertension (successfully treated for Hepatitis B or C are recommended to be evaluated by elastography or liver biopsy to evaluated for cirrhosis).
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  • Uncontrolled bacterial, viral or fungal infections (currently taking medication and with progression or no clinical improvement) at time of enrollment.
  • Another cancer in remission less than 2 yrs are not eligible. A history of a previously treated solid tumor whose remission status is 2 yrs or greater and are not receiving tumor directed therapy will be considered eligible. Hormonal therapy as a part of long-term maintenance post-malignancy is allowed.
  • Concurrent participation in another investigational clinical trial(s) with interventions which could influence relapse, GVHD, or viral reactivation.
  • Systemic corticosteroid use at the time of screening. Treatment with hydrocortisone for prevention of transfusion reactions are eligible, but use of methylprednisolone is not allowed.
  • Woman who are pregnant or lactating.
  • Any serious medical or psychiatric illness likely to interfere with participation in this clinical study.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Northside Hospital

    Atlanta, Georgia, 30432GA

  • MD Anderson

    Houston, Texas, 77030TX

Other trials in United States

About this study

This study is a Phase II, single arm, open label multicenter trial designed to investigate the use of haploidentical donor derived NK cells (K-NK002) for the treatment of patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who are undergoing haploidentical donor bone marrow transplantation (HaploBMT). K-NK002 is a NK cell product derived from peripheral blood leukocytes collected from a related donor (HLA-haploidentical matched) and enriched for NK cells with depletion of CD3+ T-lymphocytes (T-cells) followed by enriched ex-vivo expansion and administered to the patient prior to and following BMT.

Read the detailed description

The study is a Phase II, single arm, open label, multicenter trial evaluating the cumulative incidence of relapse when K-NK002 is used for relapse mitigation in patients with high-risk AML and MDS receiving an allogeneic haploidentical bone marrow graft.

Part One (Safety run-in):

An initial safety run-in to confirm the starting dose, and safety and tolerability of K-NK002;

  • Dose cohort 1 will include 3 patients who will receive a dose of K-NK002 at 1 x 10E7 NK cells per kg.
  • Dose cohort 2 will include 3 patients who will receive K-NK002 at 1 x 10E8 NK cells per kg.

Part Two (Open Enrollment):

Enrollment into the second part of the study (Open Enrollment) can begin following Part One, confirmation of dose and safety.

Being tested
K-NK002, Conditioning Regimen, HaploBMT
Keywords
K-NK002, NK cell therapy, AML, MDS
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.

  • K-NK002Biological

    K-NK002 will be administered intravenous (IV) on Day -2, Day +7 and Day +28.

    Part One (Safety run-in):

    An initial safety run-in to confirm the starting dose, and safety and tolerability of K-NK002;

    • Dose cohort 1 will include 3 patients who will receive a dose of K-NK002 at 1 x 10E7 NK cells per kg.
    • Dose cohort 2 will include 3 patients who will receive K-NK002 at 1 x 10E8 NK cells per kg.

    Part Two (Open Enrollment):

    Enrollment into the second part of the study (Open Enrollment) can begin following Part One, confirmation of dose and safety.

  • Conditioning RegimenProcedure or surgery

    From Day -7 to Day -3:

    • Melphalan: 140 mg/m2 (100mg/m2 in patients ≥ 60) on Day -7.
    • Fludarabine: 40 mg/m2 daily for 4 doses starting on days -7.
    • TBI: 2 Gy on Day -3.

  • HaploBMTProcedure or surgery

    Bone marrow is the only allowed graft source for patients enrolled in this clinical trial

Study groups in NCT04395092
Study groupRoleWhat they receive
K-NK002ExperimentalNot described
Receives: Biological: K-NK002; Procedure: Conditioning Regimen; Procedure: HaploBMT

What is being measured

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

  1. Cumulative incidence of relapse

    Cumulative incidence of relapse at 1 year

    Measured: 1 year

Secondary outcomes (12)

  1. Determine the safety and tolerability of K-NK002 through incidence of (Serious) Adverse Events.

    As assessed by CTCAE v5.0, incidence of AEs and serious adverse events (SAEs) will be collected from the 1st dose of K-NK002 through 30 days after the last dose. In addition, any SAEs assessed as related to the investigational product that occurs after the 30-day follow-up period will be recorded till end of study.

    Measured: 1-year post-transplant.

  2. Overall survival (OS).

    Measured: 1-year post-transplant.

  3. Rate of Non-Relapse Mortality (NRM).

    Measured: 1-year post-transplant.

  4. Relapse-free survival.

    Measured: 1-year post-transplant.

  5. GVHD-free survival.

    Measured: 1-year post-transplant.

  6. Cumulative incidence of grade II-IV and III-IV acute GVHD.

    Measured: Day 100 post-transplant.

  7. Cumulative incidence of chronic GVHD.

    Measured: 1-year post-transplant.

  8. Hematologic recovery as assessed according to neutrophil and platelet counts.

    • Neutrophil recovery: absolute neutrophil count (ANC) ≥ 500/mm3 for three consecutive measurements on three different days.
    • Platelet recovery: the first day of a sustained platelet count ≥ 20,000/mm3 or ≥50,000/mm3 with no platelet transfusions in the preceding seven days.

    Measured: Up to day 100 post-transplant.

  9. Donor cell engraftment.

    Frequencies and percentage of patients with full (>95%), mixed (5-95%), or low (<5%) chimerism at each time point. Mixed and full chimerism will be evidence of donor cell engraftment.

    Measured: Days 28 and 100 post-transplant.

  10. Primary and secondary graft failure as measured by neutrophil count.

    Measured: By days 28 and 100 post-transplant.

  11. Overall toxicity.

    Incidence of all grade 1-5 AE from 1st dose of K-NK002 to 30 days after the last dose of K-NK002 according to CTCAE v5.0.

    Measured: From 1st dose of K-NK002 to 30 days after last dose.

  12. Cumulative incidence of CMV reactivation and symptomatic BKV hemorrhagic. cystitis.

    Measured: Days 100 and 180 post-transplant.

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 2020
  2. Study start13 Nov 2020
  3. Primary completionNov 2022 (estimated)
  4. Study completionNov 2023 (estimated)

Why it stopped: The sponsor decided to withdraw this 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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04395092
Sponsor's protocol ID
BMT CTN 1803
Other IDs
U24HL138660
Status last verified
Jun 2021
First submitted
6 May 2020
Last updated
22 Jun 2021
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 K-NK002, Conditioning Regimen and HaploBMT in people with Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS), run by Kiadis Pharma at 2 sites in United States.

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 25 inclusion and 12 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 22 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

Cumulative incidence of relapse (time frame: 1 year). 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 NCT04395092.

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 22 Jun 2021.

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