Phase 2 STIR Trial: Haploidentical Transplant and Donor Natural Killer Cells for Solid Tumors

NCT02100891 | Terminated Phase 2 Results DMC

• 1 other identifier: STIR Trial
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief 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 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.

Conditions

Ewing Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Osteosarcoma; CNS Tumors

Keywords

Ewing Sarcoma; Neuroblastoma; Rhabdomyosarcoma; Osteosarcoma; CNS tumors; Brain Tumors

Outcome Measures

Primary Outcomes (1)

• 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

  6 months

Secondary Outcomes (4)

• Overall Survival

  1 year

• Grades 3-4 GVHD

  Day +100

• Non-relapse Mortality

  Day +100

• Progression-free Survival

  6 months

Study Arms (1)

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.

Procedure: Allogeneic HCT; Drug: Donor NK Cell Infusion

Interventions

Allogeneic HCT PROCEDURE

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.

Also known as: Haplo transplant, Reduced-intensity conditioning, Bone marrow transplant

Allogeneic HCT + Donor NK Cell Infusion

Donor NK Cell Infusion DRUG

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.

Also known as: Natural Killer Cells, Adoptive immunotherapy, Donor Lymphocyte Infusion, IND 13794

Allogeneic HCT + Donor NK Cell Infusion

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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:
• 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

Sponsors & Collaborators

• Monica Thakar: lead

Study Sites (2)

Children's Hospital of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Froedtert and The Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 31401903 DERIVED

MeSH Terms

Conditions

Sarcoma, Ewing; Neuroblastoma; Rhabdomyosarcoma; Osteosarcoma; Central Nervous System Neoplasms; Brain Neoplasms

Interventions

Bone Marrow Transplantation; IL32 protein, human; Immunotherapy, Adoptive

Condition Hierarchy (Ancestors)

Neoplasms, Bone Tissue; Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Myosarcoma; Neoplasms, Muscle Tissue; Nervous System Neoplasms; Neoplasms by Site; Nervous System Diseases; Brain Diseases; Central Nervous System Diseases

Intervention Hierarchy (Ancestors)

Tissue Transplantation; Cell- and Tissue-Based Therapy; Biological Therapy; Therapeutics; Transplantation; Surgical Procedures, Operative; Adoptive Transfer; Immunization, Passive; Immunization; Immunotherapy; Immunomodulation; Immunologic Techniques; Investigative Techniques

Limitations and Caveats

Early termination due to low accrual at end of study leading to lower number of subjects analyzed than expected.

Results Point of Contact

• Title: Monica Thakar, MD - Professor of Pediatrics
• Organization: Fred Hutchinson Cancer Center

isioc@fredhutch.org

206-667-5000

Study Officials

• Monica Thakar, MD

  Medical College of Wisconsin

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Pediatrics Blood and Marrow Transplant Program

Study Record Dates

• First Submitted: March 27, 2014
• First Posted: April 1, 2014
• Study Start: March 20, 2013
• Primary Completion: June 8, 2020
• Study Completion: July 15, 2020
• Last Updated: March 19, 2025
• Results First Posted: March 19, 2025

Record last verified: 2025-02

Locations

US (2)