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Ewing SarcomaPhase 1/2NKEXPSARCNCT02409576

Pilot Study of Expanded , Activated Haploidentical Natural Killer Cell Infusions for Sarcomas

A Phase 1/2 study testing Expanded , Activated NK cells in people with Ewing Sarcoma and Rhabdomyosarcoma, run by National University Hospital, Singapore at 1 site in Singapore.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Progress in the treatment of children with leukemia and lymphoma results in high cure rates but progress in the treatment of children and adolescents with solid tumors has been slow. Read more about this study

Who is it for?
Ages Up to 80 years
Conditions the study is for
Ewing Sarcoma, Rhabdomyosarcoma
What is being tested?
Expanded , Activated NK cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteSingapore
Study dates
Feb 2015to Sep 2020
Phase
Phase 1/2
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 Up to 80 years
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Who may be able to join

  • A ) NK cell Recipient:
  • Age 0 months to 80 years old.
  • Patients with metastatic, progressive or relapsed EWS, RMS after completing standard of care therapy who are at high risk of relapse even if they do not have any evidence of residual disease.
  • For patients without residual disease at the point of study entry, response to NK cells will be measured by their incidence of relapse as indicated by their 5-year event free survival. Only patients at high risk of relapse > 70% will be enrolled if there is no evidence of residual disease.
  • Shortening fraction greater than or equal to 25%. Left ventricular ejection fraction (LVEF) greater than or equal to 40%
  • Glomerular filtration rate greater than or equal to 60 ml/min/1.73 m2.
Show all 26Show fewer
  • Pulse oximetry greater than or equal to 92% on room air.
  • Direct bilirubin less than or equal to 3.0 mg/dL (50 mmol/L).
  • Alanine aminotransferase (ALT) is no more than 2 times the upper limit of normal.
  • Aspartate transaminases (AST) is no more than 2 times the upper limit of normal.
  • Karnofsky or Lansky performance score of greater than or equal to 50.
  • Does not have a current pleural or pericardial effusion.
  • Has a suitable adult family member donor available for NK cell donation.
  • Has recovered from all acute NCI Common Terminology Criteria for Adverse Events (CTCAE) grade II-IV non-hematologic acute toxicities resulting from prior therapy per the judgment of the PI.
  • At least two weeks since receipt of any biological therapy, systemic chemotherapy, and/or radiation therapy.
  • Is not receiving more than the equivalent of prednisone 10 mg daily.
  • Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
  • Not lactating.
  • NK cell Donor:
  • First and second degree relative acceptable.
  • 18 years of age or above.
  • Not lactating.
  • Greater than or equal to 3 of 6 HLA match to recipient.
  • Meets eligibility and suitability criteria for hematopoietic cells donation as per institutional guidelines.
  • Not pregnant (negative serum or urine pregnancy test to be conducted within 7 days prior to enrollment).
  • HIV negative. Negative results must be within 60 days prior to enrolment.

Who cannot join

  • Failure to meet any of the inclusion criteria.

Trial locations and contacts

1 site in 1 country.

Bernice Oh Lingzhi, MBBS contact

(65)97739114

bernice_lx_oh@nuhs.edu.sg

Singapore1 site, 1 recruiting

  • National University Hospital

    Singapore, 119228

    Bernice Oh, (65) 97739114, bernice_lx_oh@nuhs.edu.sg

    Clarice Chan, (65) 67726586, chan_zi_ying_clarice@nuhs.edu.sg

    Recruiting

Other trials in Singapore

About this study

Progress in the treatment of children with leukemia and lymphoma results in high cure rates but progress in the treatment of children and adolescents with solid tumors has been slow. Despite aggressive therapy with multimodality treatment involving surgery, radiation and chemotherapy, about two thirds of the patients with metastatic Ewing sarcoma (EWS), and intermediate and high risk rhabdomyosarcoma (RMS) will relapse. The available second line therapies for relapse are limited and often not effective. There is a dire need to look for treatment options beyond conventional means for the treatment of these patients.

Infusions of allogeneic natural killer (NK) cells in leukemia patients have shown to be tolerated well without inducing graft versus host disease (GVHD). There is also mounting evidence that NK cells have activity against solid tumors.

Read more

In the lab the investigators tested NK cell activity against cell lines from different paediatric solid tumors. Among paediatric solid tumors, EWS and RMS are exquisitely sensitive to killing by expanded NK cells; NK cells also have activity against OS cells. Preliminary clinical data suggest that donor NK cells may exert antitumor activity in children with solid tumors undergoing allogeneic hematopoietic stem cell transplantation.

Taking into account the safety of adaptive NK cell infusion, and their efficacy against EWS, RMS and OS, NK cells could be a powerful new tool in the treatment of paediatric solid tumors.

The great anti-tumor activity of expanded and activated NK cells, together with the feasibility of infusing haploidentical NK cells in a non-transplant setting form a compelling rationale for the clinical testing of these NK cells in patients with sarcoma.

Read the detailed description

Adoptive transfer of allogeneic NK cells has been shown to be safe in patients with leukemia.

The patients enrolled on this will receive lymphodepleting chemotherapy with cyclophosphamide (1 day) followed by fludarabine (5 days) Each patient will receive IL-2 on alternate days starting 1 day before infusion of NK cells for a total of 6 doses.

Patient will undergo imaging MRI or PET or CT scan one month after the infusion to assess response to the NK cell infusion.

In our study we aim to determine the feasibility, safety and efficacy of expanded, activated NK cells in patients with EWS and RMS .

We will also study the persistence and phenotype of expanded NK cells in research participants with EWS and RMS .

The main hypothesis to be tested in this study is that infusion of expanded, activated haploidentical NK cells can produce measurable clinical responses in patients with EWS and RMS .

Being tested
Expanded , Activated NK cells
Keywords
EWS, RMS
Medical subject headings
Sarcoma, Ewing, Rhabdomyosarcoma

What participants receive

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

  • Expanded , Activated NK cellsBiological

    1. Chemotherapy - Each patient will receive immunosuppressive chemotherapy before infusion of NK cells. Day -7 Cyclophosphamide at 60mg/kg Day -6 Fludarabine at 25mg/m2 daily for 5 days
    2. Radiation - Each patient will receive radiation within 48 hr of NK cell infusion to make the tumor cells more sensitive to NK cell killing Radiation 2Gy
    3. Cytokine support - Each pateint will receive IL-2 to support NK cell activation and expansion in vivo Day -1 alternate day for a total of 6 doses
    4. NK cells - Expanded activated haploidentical NK cells will be infused on day 0.
Study groups in NCT02409576
Study groupRoleWhat they receive
Expanded, activated NK Cells(NKEXPSARC)ExperimentalIntravenous infusion of expanded, activated NK Cells Donor cell will be expanded and activated in the cGMP compliant TECT lab for 10 to 12 days prior to infusion into the patient.
Receives: Biological: Expanded , Activated NK cells

What is being measured

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

  1. Disease response after expanded activated NK cell infusion

    Radiological response will be measured based on PET or MRI or CT scan whichever is appropriate imaging for the tumor type and location.

    Measured: 1 month post-NK cell infusion (and at regular intervals thereafter till a year post-NK cell infusion)

Secondary outcomes (4)

  1. Persistence and phenotype of expanded NK cells in research participants with EWS, RMS and OS.

    NK cell persistence and phenotype will be monitored weekly upto 4 weeks post infusion from peripheral blood.

    Measured: 1 month ( 30 days) post- NK cell infusion

  2. Toxicity of NK cells infusion (NCI toxicity criteria CTC version 4.0)

    Patients will be monitored for toxicity based on NCI toxicity criteria CTC version 4.0

    Measured: 1 month ( 30 days) post- NK cell infusion

  3. Performance status will be assessed by age-dependent Performances Scores ( Lansky scale or Karnofsky performance scale)

    Patients performance status will be monitored using Lansky scale for patients below 16 years of age and Karnofsky performance scale for patients more than 16 years of age.

    Measured: Initiation of conditioning till 30 days post-NK cell infusion

  4. Acute and Chronic GVHD

    Patients will monitored for clinical evidence of GVHD

    Measured: Initiation of conditioning until 1 month ( 30 days) post- last dose of IL-2

Timeline

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

  1. First posted7 Apr 2015 (estimated)
  2. Study startFeb 2015
  3. Primary completionAug 2020 (estimated)
  4. Study completionSep 2020 (estimated)

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 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02409576
Sponsor's protocol ID
DSRB 2014/00452
Other IDs
CTC1400413 (NUH), CTC1400412 (KKWCH)
Acronym
NKEXPSARC
Status last verified
Apr 2019
First submitted
1 Apr 2015
Last updated
16 Apr 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • Cho D, Shook DR, Shimasaki N, Chang YH, Fujisaki H, Campana D. Cytotoxicity of activated natural killer cells against pediatric solid tumors. Clin Cancer Res. 2010 Aug 1;16(15):3901-9. doi: 10.1158/1078-0432.CCR-10-0735. Epub 2010 Jun 11.

    PubMed 20542985

  • Perez-Martinez A, de Prada Vicente I, Fernandez L, Gonzalez-Vicent M, Valentin J, Martin R, Maxwell H, Sevilla J, Vicario JL, Diaz MA. Natural killer cells can exert a graft-vs-tumor effect in haploidentical stem cell transplantation for pediatric solid tumors. Exp Hematol. 2012 Nov;40(11):882-891.e1. doi: 10.1016/j.exphem.2012.07.004. Epub 2012 Jul 4.

    PubMed 22771496

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Expanded , Activated NK cells in people with Ewing Sarcoma and Rhabdomyosarcoma, run by National University Hospital, Singapore at 1 site in Singapore.

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 26 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 16 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Singapore. 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Results are not available in the source record.

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

Contact Bernice Oh Lingzhi, MBBS ((65)97739114, bernice_lx_oh@nuhs.edu.sg), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease response after expanded activated NK cell infusion (time frame: 1 month post-NK cell infusion (and at regular intervals thereafter till a year post-NK cell infusion)). 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 NCT02409576, which also lists 2 linked publications.

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 16 Apr 2019.

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