Ewing SarcomaPhase 2STIRNCT02100891
Phase 2 STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors
A Phase 2 study testing Allogeneic HCT and Donor NK Cell Infusion in people with Ewing Sarcoma and Neuroblastoma, run by Monica Thakar at 2 sites in United States.
Trial summary
The investigators hypothesize that this Phase 2 cellular and adoptive immunotherapy study using human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) followed by an early, post-transplant infusion of donor natural killer (NK) cells on Day +7 will not only be well-tolerated in this… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma
- What is being tested?
- Allogeneic HCT and Donor NK Cell Infusion
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 2 sitesUnited States
- Study dates
- 20 Mar 2013to 15 Jul 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- No age restrictions
- Only subjects who are not appropriate candidates for autologous or HLA-matched sibling hematopoietic cell transplants (HCT) may be enrolled.
- Diseases eligible
- High Risk Neuroblastoma (NB): Must have progressed on or recurred after standard frontline therapy including autologous HCT, or be ineligible for autologous HCT.
- Ewing Sarcoma Family of Tumors (EWS) [includes both bone and soft tissue Ewing and Peripheral Primitive Neuroectodermal Tumors (PNET)]. Must have progressed on or recurred after standard frontline therapy which includes doxorubicin and ifosfamide.
- High-Risk Rhabdomyosarcoma (RMS) or Intermediate Risk Alveolar RMS recurring as more than loco-regional tumor: Must have progressed on or recurred after standard frontline therapy which includes chemotherapy with vincristine, actinomycin, and cyclophosphamide AND either surgery or radiotherapy.
- Osteosarcoma: Must have progressed or recurred after standard frontline therapy. If first relapse, must have recurred with a) ≥ 4 lung nodules; b) bilateral lung involvement; or c) relapse outside the lungs.
- CNS tumors: High risk malignant brain tumors that are recurrent or refractory to standard frontline therapy are eligible. Diagnoses include: Medulloblastoma, primitive neuro-ectodermal tumor (PNET), ependymoma, high grade (grade 3 or 4) glioma/astrocytoma, germ-cell tumor, or atypical teratoid-rhabdoid tumor (ATRT)
Who cannot join
- Rapidly-progressing disease prior to HCT, defined as clinical or radiographic evidence of disease progression ≤ 3 weeks prior to protocol registration despite previous achievement of stable or no disease (Appendix C \& D) (Note: after disease eligibility has been determined, additional imaging studies are not necessary during the three weeks before the start of conditioning unless there are clinical concerns).
- Patients who have reached radiation threshold limits and are excluded from receiving 3 Gy TBI.
- Diffuse intrinsic pontine gliomas (DIPG) are excluded.
- Performance status: Karnofsky or Lansky <60% Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients, who in the opinion of the investigator, may not be able to comply with the treatment plan or safety monitoring requirements of the study Page 16 of 86 Children's Hospital of Wisconsin Medical College of Wisconsin PI: Monica S. Thakar, MD
- Significant organ dysfunction that would prevent compliance with conditioning, GVHD prophylaxis, or would severely limit the probability of survival, defined as:
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- Cardiac: For patients not taking inotropic medications and who do not have cardiac failure requiring therapy: Symptomatic coronary artery disease or ejection fraction <35% or, if unable to obtain ejection fraction, shortening fraction of <26%. If shortening fraction is <26% a cardiology consult is required with the PI having final approval of eligibility. For patients taking inotropic medications: Patients displaying corrected cardiac function will be eligible, i.e., patients who take inotropic medications to maintain EF ≥ 35% and SF≥ 26% cardiac function eligibility.
- Pulmonary: DLCO <40% TLC <40%, FEV1 <40% and/or receiving supplementary continuous oxygen
- Liver: Patient with clinical or laboratory evidence of liver disease will be evaluated for the cause of liver disease, its clinical severity in terms of liver function, bridging fibrosis, and the degree of portal hypertension. The patient will be excluded if he/she is found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evinced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin >3mg/dL, or symptomatic biliary disease
- Patients with serious active infections
- HIV seropositive patients
- Patients with poorly controlled hypertension despite multiple antihypertensive medications
- Fertile females who are unwilling to use contraceptive techniques during and for the twelve months following treatment, as well as females who are pregnant or actively breast feeding
- Fertile males who are unwilling to use contraceptive techniques during and for the twelve months following treatment
- Life expectancy severely limited by diseases other than malignancy
- Patients who have received a prior allogeneic HCT are ineligible
- DONOR SELECTION An Unrelated Donor Search is not required for entry on this trial. Lack of HLA-matched related or unrelated donors is not a requirement for entry on this trial.
- Inclusion Criteria
- Related, HLA-haploidentical donors who are identical for one HLA haplotype and mismatched for any number of HLA-A, -B, -C, DRB1 or DQB1 loci of the unshared haplotype.
- Marrow will be prioritized as the hematopoietic stem cell source of choice. In cases where adequate stem cells cannot be collected, fresh (preferred) or cryopreserved donor PBSC may be substituted. In the case that PBSC are used, the donor must be 18 years of age or older.
- HLA-haploidentical donor selection will be based on standard institutional criteria; otherwise no specific prioritization will be made amongst the suitable available donors.
- Exclusion Criteria
- Children less than 12 years of age (marrow) or less than 18 years of age (PBSC).
- Children greater than or equal to 12 years of age who have not provided informed assent in the presence of a parent and an Attending physician who is not a member of the recipient's care team
- Children greater than or equal to 12-17.9 years of age who have inadequate peripheral vein access to safely undergo apheresis
- Donors unable or unwilling to undergo marrow harvest or PBSC collection for the initial HCT, storage of autologous blood prior to marrow harvest (if applicable), or apheresis one week after marrow harvest
- Donors who are not expected to meet the minimum target dose of marrow cells (1 x 108 total nucleated cells/kg recipient weight) for the initial marrow HCT or PBSC transplant (5.0 x 106 CD34/kg recipient weight). The average nucleated cell content of harvested marrow is 22 x 106 nucleated cells/mL or 220 x 108 total nucleated cells/Liter
- HIV-positive donors
- Donors who are cross-match positive with recipient
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital of Wisconsin
Milwaukee, Wisconsin, 53226
Froedtert and The Medical College of Wisconsin
Milwaukee, Wisconsin, 53226
About this study
Official title: Phase 2 Solid Tumor Immunotherapy Trial Using HLA-Haploidentical Transplant and Donor Natural Killer Cells: The STIR Trial
The investigators hypothesize that this Phase 2 cellular and adoptive immunotherapy study using human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) followed by an early, post-transplant infusion of donor natural killer (NK) cells on Day +7 will not only be well-tolerated in this heavily-treated population (safety), but will also provide a mechanism to treat high-risk solid tumors, leading to improved disease control rate (efficacy). Disease control rate is defined as the combination of complete (CR) and partial (PR) response and stable disease (SD). The investigators further propose that this infusion of donor NK cells will influence the development of particular NK and T cell subtypes which will provide immediate/long-term tumor surveillance, infectious monitoring, and durable engraftment.
Patients with high-risk solid tumors (Ewings Sarcoma, Neuroblastoma and Rhabdomyosarcoma) who have either measurable or unmeasurable disease and have met eligibility will be enrolled on this trial for a goal enrollment of 20 patients over 4 years.
Read the detailed description
Patients will receive a reduced-intensity conditioning regimen for 6 days that consists of Fludarabine 150 mg/m2, Cyclophosphamide 29 mg/kg, and 3 Gy total body irradiation (TBI), followed by HLA-haploidentical marrow from a family member on Day 0. On Days +3 and +4, Cyclophosphamide 50 mg/kg will be infused for selective in vivo T cell depletion. Additional post-grafting immune suppression will consist of mycophenolate mofetil and either tacrolimus or sirolimus.
Non-mobilized peripheral blood mononuclear cells will be collected from donors on Day +6, from which NK cells will be selected and infused into patients on Day +7.
Patients will be monitored for any transplant-related complications and will undergo disease monitoring every three months for the first two years post-transplant. Research studies will be conducted to follow the patient's immune status and quality of life post-transplant.
- Conditions
- Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma, Osteosarcoma, CNS Tumors
- Being tested
- Allogeneic HCT, Donor NK Cell Infusion
- Keywords
- Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma, Osteosarcoma, CNS tumors, Brain Tumors
- Medical subject headings
- Sarcoma, Ewing, Neuroblastoma, Rhabdomyosarcoma, Osteosarcoma, Central Nervous System Neoplasms, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Allogeneic HCTProcedure or surgery
Also called Haplo transplant, Reduced-intensity conditioning, Bone marrow transplant
Patients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant.
Donor NK Cell InfusionDrug
Also called Natural Killer Cells, Adoptive immunotherapy, Donor Lymphocyte Infusion, IND 13794
Patients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant.
| Study group | Role | What they receive |
|---|---|---|
| Allogeneic HCT + Donor NK Cell Infusion | Experimental | Patients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant. Receives: Procedure: Allogeneic HCT; Drug: Donor NK Cell Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Disease-control Rate
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
Measured: 6 months
Secondary outcomes (4)
Overall Survival
Number of subjects alive at 1 year post-HCT
Measured: 1 year
Grades 3-4 GVHD
The presence of severe acute grades 3-4 GVHD by day +100
Measured: Day +100
Non-relapse Mortality
Death from causes other than disease by day +100
Measured: Day +100
Progression-free Survival
Alive without progression or relapse of disease by 6 months post-HCT
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Apr 2014 (estimated)
- Study start20 Mar 2013
- Primary completion8 Jun 2020
- Study completion15 Jul 2020
Why it stopped: 15 patients enrolled out of planned 20, terminated due to slow enrollment at end of study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ewing SarcomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Monica Thakar
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Monica Thakar, Medical College of Wisconsin
- Investigators
- Monica Thakar, MD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02100891
- Sponsor's protocol ID
- STIR Trial
- Acronym
- STIR
- Status last verified
- Feb 2025
- First submitted
- 27 Mar 2014
- Last updated
- 19 Mar 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
PubMed 31401903
Study at a glance
From the registry record, last updated by the sponsor on 19 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 2 Solid Tumor Immunotherapy Trial Using HLA-Haploidentical Transplant and Donor Natural Killer Cells: The STIR Trial
- ClinicalTrials.gov ID
- NCT02100891
- Acronym / sponsor ID
- STIR / STIR Trial
- Conditions
- Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma, Osteosarcoma, CNS Tumors
- Keywords
- Ewing Sarcoma, Neuroblastoma, Rhabdomyosarcoma, Osteosarcoma, CNS tumors, Brain Tumors
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: 15 patients enrolled out of planned 20, terminated due to slow enrollment at end of study
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Monica ThakarUniversity, hospital or other
- Study start
- 20 Mar 2013 (actual)
- Primary completion
- 8 Jun 2020 (actual)
- Study completion
- 15 Jul 2020 (actual)
- First posted
- 1 Apr 2014 (estimated)
- Results
- Posted 19 Mar 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators hypothesize that this Phase 2 cellular and adoptive immunotherapy study using human leukocyte antigen (HLA)-haploidentical hematopoietic cell transplantation (HCT) followed by an early, post-transplant infusion of donor natural killer (NK) cells on Day +7 will not only be well-tolerated in this heavily-treated population (safety), but will also provide a mechanism to treat high-risk solid tumors, leading to improved disease control rate (efficacy). Disease control rate is defined as the combination of complete (CR) and partial (PR) response and stable disease (SD). The investigators further propose that this infusion of donor NK cells will influence the development of particular NK and T cell subtypes which will provide immediate/long-term tumor surveillance, infectious monitoring, and durable engraftment.
Patients with high-risk solid tumors (Ewings Sarcoma, Neuroblastoma and Rhabdomyosarcoma) who have either measurable or unmeasurable disease and have met eligibility will be enrolled on this trial for a goal enrollment of 20 patients over 4 years.
Detailed description
Patients will receive a reduced-intensity conditioning regimen for 6 days that consists of Fludarabine 150 mg/m2, Cyclophosphamide 29 mg/kg, and 3 Gy total body irradiation (TBI), followed by HLA-haploidentical marrow from a family member on Day 0. On Days +3 and +4, Cyclophosphamide 50 mg/kg will be infused for selective in vivo T cell depletion. Additional post-grafting immune suppression will consist of mycophenolate mofetil and either tacrolimus or sirolimus.
Non-mobilized peripheral blood mononuclear cells will be collected from donors on Day +6, from which NK cells will be selected and infused into patients on Day +7.
Patients will be monitored for any transplant-related complications and will undergo disease monitoring every three months for the first two years post-transplant. Research studies will be conducted to follow the patient's immune status and quality of life post-transplant.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Allogeneic HCT + Donor NK Cell Infusion | Experimental | Procedure: Allogeneic HCT, Drug: Donor NK Cell InfusionPatients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (8 listed)
- No age restrictions
- Only subjects who are not appropriate candidates for autologous or HLA-matched sibling hematopoietic cell transplants (HCT) may be enrolled.
- Diseases eligible
Key exclusion criteria (29 listed)
- Rapidly-progressing disease prior to HCT, defined as clinical or radiographic evidence of disease progression ≤ 3 weeks prior to protocol registration despite previous achievement of stable or no disease (Appendix C \& D) (Note: after disease eligibility has been determined, additional imaging studies are not necessary during the three weeks before the start of conditioning unless there are clinical concerns).
- Patients who have reached radiation threshold limits and are excluded from receiving 3 Gy TBI.
- Diffuse intrinsic pontine gliomas (DIPG) are excluded.
- Performance status: Karnofsky or Lansky <60% Note: Patients who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score
- Patients, who in the opinion of the investigator, may not be able to comply with the treatment plan or safety monitoring requirements of the study Page 16 of 86 Children's Hospital of Wisconsin Medical College of Wisconsin PI: Monica S. Thakar, MD
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Allogeneic HCTAlso: Haplo transplant, Reduced-intensity conditioning, Bone marrow transplantPatients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant. | Procedure or surgery | Allogeneic HCT + Donor NK Cell Infusion |
| Donor NK Cell InfusionAlso: Natural Killer Cells, Adoptive immunotherapy, Donor Lymphocyte Infusion, IND 13794Patients will undergo HLA-haploidentical bone marrow transplant preceded by reduced-intensity chemotherapy and radiation therapy, followed by donor NK cells on day +7 after transplant. | Drug | Allogeneic HCT + Donor NK Cell Infusion |
Primary outcome
Disease-control Rate
Time frame: 6 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
4 secondary outcomes
Overall Survival
Time frame: 1 year
Grades 3-4 GVHD
Time frame: Day +100
Non-relapse Mortality
Time frame: Day +100
Progression-free Survival
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Mar 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 31401903Hattinger CM, Patrizio MP, Magagnoli F, Luppi S, Serra M. An update on emerging drugs in osteosarcoma: towards tailored therapies? Expert Opin Emerg Drugs. 2019 Sep;24(3):153-171. doi: 10.1080/14728214.2019.1654455. Epub 2019 Aug 14.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Monica Thakar, MD principal investigator
Medical College of Wisconsin
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Allogeneic HCT and Donor NK Cell Infusion in people with Ewing Sarcoma and Neuroblastoma, run by Monica Thakar 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 8 inclusion and 29 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: stopped early, as of the sponsor's last update on 19 Mar 2025. 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?
Yes. Results are posted in the registry (first posted 19 Mar 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Disease-control Rate (time frame: 6 months). 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 NCT02100891, which also lists 1 linked publication.
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 19 Mar 2025.