RECRUITING

NANT 2021-01 Phase II STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial

Conditions

Neuroblastoma Relapsed Neuroblastoma Refractory Neuroblastoma Cellular Therapy Immunotherapy Chemoimmunotherapy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is a phase II study looking at patient response to treatment with the combination dinutuximab, temozolomide, irinotecan, and GM-CSF.

Official Title

Phase II Study of Ex-Vivo Expanded Allogeneic Universal Donor TGFβi NK Cell Infusions in Combination With Temozolomide, Irinotecan, Dinutuximab, and Sargramostim in Patients With Relapsed or Refractory Neuroblastoma The STING (Sequential Temozolomide, Irinotecan, NK Cells and GD2 mAb) Trial

Quick Facts

Study Start:2024-12-16

Study Completion:2038-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06450041

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:1 Year to 31 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must be ≥ 1 year and ≤31 years of age at the time of enrollment on the study. * Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines. * Patients must have high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients whose disease was initially considered low or intermediate risk but then reclassified as high-risk neuroblastoma prior to enrollment also meet this criteria. * Patients must have at least ONE of the following: * Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below) based on institutional assessment: 1. a) MIBG avid tumors: patients must meet one of the following criteria: 1. SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for discrete lymph nodes ≥ 15mm on short axis. Lesions meeting size criteria will be considered measurable. 2. In addition to size, a lesion needs to meet ONE of the following criteria except for patients with parenchymal CNS lesions which will only need to meet size criteria: 1. For MIBG avid tumors: lesion must be MIBG avid and meet one of the following criteria: 1. For patients with recurrent/progressive or refractory disease: 2. For patients with persistent disease: * Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 50 (Appendix I). * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration. * Patients must not have received the therapies indicated below after disease evaluation or within the specified time period prior to registration on this study as follows: 1. Myelosuppressive chemotherapy: must not have received within 2 weeks prior to registration. 2. Biologic anti-neoplastics- agents not known to be associated with reduced platelet or ANC counts (including retinoids): must not have received within 7 days prior to registration. 3. Monoclonal antibodies: must not have received last dose within 14 days of registration and resolution of all toxicities. 4. Cellular Therapy (e.g. modified T cells, NK cells, dentritic cells etc.): must not have received within 3 weeks and resolution of all toxicities. 5. Radiation: must not have received small port radiation within 7 days prior to registration, large field radiation within 12 weeks, and 131I-MIBG therapy or other radiopharmaceutical within 6 weeks. 6. Hematopoietic Stem Cell Transplant- none following myeloblative therapy within 6 weeks 7. Any other investigational agents (covered under another IND within 14 days 8. Strong inducers or inhibitors of CYP3A4 * Hematologic Function: 1. Absolute Neutrophil count ≥750/µL 2. Platelet count ≥ 75,000/µL, transfusion independent (no platelet transfusions within 7 days of blood draw documenting eligibility) * Renal Function Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age * Liver Function 1. Total bilirubin ≤ 1.5 x ULN for age; and, 2. SGPT (ALT) ≤ 135 U/L (≤ 3x ULN). Note that for ALT, the upper limit of normal for all sites is defined as 45 U/L. * Cardiac Function 1. Normal ejection fraction (≥ 55%) documented by either echocardiogram OR 2. Normal fractional shortening (≥ 27%) documented by echocardiogram * Pulmonary Function No evidence of dyspnea at rest * Reproductive Function All females ≥ Tanner stage 2 and post-menarchal of childbearing potential must have a negative beta-HCG within 7 days prior to study registration. Males and females of reproductive age and childbearing potential must commit to using effective contraception for the duration of their participation. * Central Nervous System (CNS) Patients with a history of intraparenchymal or leptomeningeal based CNS disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.	* Patients who are pregnant, breast feeding, or unwilling to use effective contraception during the study * Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study. * Patients with disease of any major organ system that would compromise their ability to withstand therapy. * Patients with \> Grade 2 diarrhea. * Patients who have undergone a prior allogeneic stem cell or solid organ transplant. * Patients who are on hemodialysis. * Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria. * Patients with known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion. * Patients must not have been diagnosed with any other malignancy. * Patients with history of Grade 4 Allergic reactions to anti-GD2 antibody therapy or reactions that caused permanent discontinuation of therapy. * Patients with history of progressive disease while receiving therapy per ANBL1221. * Patient declines participation in the NANT biology study and the site has not been granted a waiver from participation. * Systemic Steroids and Immunosuppressive Medications * Patients who have received pharmacologic doses of systemic steroids 7 days prior to study registration or likely to require them after study registration. 1. Patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration. 2. The use of conventional doses of inhaled steroids for the treatment of asthma 3. The use of physiologic doses of steroids for patients with known adrenal insufficiency. * Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) at the time of study registration.

Inclusion Criteria

Exclusion Criteria

* Patients must be ≥ 1 year and ≤31 years of age at the time of enrollment on the study.
* Patients must have a diagnosis of neuroblastoma either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
* Patients must have high-risk neuroblastoma according to COG risk classification at the time of study registration. Patients whose disease was initially considered low or intermediate risk but then reclassified as high-risk neuroblastoma prior to enrollment also meet this criteria.
* Patients must have at least ONE of the following:
* Patients must have at least ONE of the following (lesions may have received prior radiation therapy as long as they meet the other criteria listed below) based on institutional assessment:
1. a) MIBG avid tumors: patients must meet one of the following criteria:
1. SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for discrete lymph nodes ≥ 15mm on short axis. Lesions meeting size criteria will be considered measurable.
2. In addition to size, a lesion needs to meet ONE of the following criteria except for patients with parenchymal CNS lesions which will only need to meet size criteria:
1. For MIBG avid tumors: lesion must be MIBG avid and meet one of the following criteria:
1. For patients with recurrent/progressive or refractory disease:
2. For patients with persistent disease:
* Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 50 (Appendix I).
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration.
* Patients must not have received the therapies indicated below after disease evaluation or within the specified time period prior to registration on this study as follows:
1. Myelosuppressive chemotherapy: must not have received within 2 weeks prior to registration.
2. Biologic anti-neoplastics- agents not known to be associated with reduced platelet or ANC counts (including retinoids): must not have received within 7 days prior to registration.
3. Monoclonal antibodies: must not have received last dose within 14 days of registration and resolution of all toxicities.
4. Cellular Therapy (e.g. modified T cells, NK cells, dentritic cells etc.): must not have received within 3 weeks and resolution of all toxicities.
5. Radiation: must not have received small port radiation within 7 days prior to registration, large field radiation within 12 weeks, and 131I-MIBG therapy or other radiopharmaceutical within 6 weeks.
6. Hematopoietic Stem Cell Transplant- none following myeloblative therapy within 6 weeks
7. Any other investigational agents (covered under another IND within 14 days
8. Strong inducers or inhibitors of CYP3A4
* Hematologic Function:
1. Absolute Neutrophil count ≥750/µL
2. Platelet count ≥ 75,000/µL, transfusion independent (no platelet transfusions within 7 days of blood draw documenting eligibility)
* Renal Function Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age
* Liver Function
1. Total bilirubin ≤ 1.5 x ULN for age; and,
2. SGPT (ALT) ≤ 135 U/L (≤ 3x ULN). Note that for ALT, the upper limit of normal for all sites is defined as 45 U/L.
* Cardiac Function
1. Normal ejection fraction (≥ 55%) documented by either echocardiogram OR
2. Normal fractional shortening (≥ 27%) documented by echocardiogram
* Pulmonary Function No evidence of dyspnea at rest
* Reproductive Function All females ≥ Tanner stage 2 and post-menarchal of childbearing potential must have a negative beta-HCG within 7 days prior to study registration. Males and females of reproductive age and childbearing potential must commit to using effective contraception for the duration of their participation.
* Central Nervous System (CNS) Patients with a history of intraparenchymal or leptomeningeal based CNS disease must have no clinical or radiological evidence of active CNS disease at the time of study enrollment.

* Patients who are pregnant, breast feeding, or unwilling to use effective contraception during the study
* Patients who, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study.
* Patients with disease of any major organ system that would compromise their ability to withstand therapy.
* Patients with \> Grade 2 diarrhea.
* Patients who have undergone a prior allogeneic stem cell or solid organ transplant.
* Patients who are on hemodialysis.
* Patients with an active or uncontrolled infection. Patients on prolonged antifungal therapy are still eligible if they are culture negative, afebrile, and meet other organ function criteria.
* Patients with known history of human immunodeficiency virus (HIV) infection, hepatitis B, or hepatitis C. Testing is not required in the absence of clinical findings or suspicion.
* Patients must not have been diagnosed with any other malignancy.
* Patients with history of Grade 4 Allergic reactions to anti-GD2 antibody therapy or reactions that caused permanent discontinuation of therapy.
* Patients with history of progressive disease while receiving therapy per ANBL1221.
* Patient declines participation in the NANT biology study and the site has not been granted a waiver from participation.
* Systemic Steroids and Immunosuppressive Medications
* Patients who have received pharmacologic doses of systemic steroids 7 days prior to study registration or likely to require them after study registration.
1. Patients known to require 2 mg/kg or less of hydrocortisone (or an equivalent dose of an alternative corticosteroid) as premedication for blood product administration.
2. The use of conventional doses of inhaled steroids for the treatment of asthma
3. The use of physiologic doses of steroids for patients with known adrenal insufficiency.
* Patients on any other immunosuppressive medications (e.g., cyclosporine, tacrolimus) at the time of study registration.

Contacts and Locations

Study Contact

Araz Marachelian, MD

CONTACT

3233615687

nantops@chla.usc.edu

Principal Investigator

Keri Streby, MD

STUDY_CHAIR

Nationwide Children's Hospital

Mark Ranalli, MD

STUDY_CHAIR

Nationwide Children's Hospital

Study Locations (Sites)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700

United States

UCSF Benioff Children's Hospital

San Francisco, California, 94143

United States

Children's Hospital Colorado

Aurora, Colorado, 80045

United States

Comer Children's Hospital, University of Chicago

Chicago, Illinois, 60614

United States

Boston Children's Hospital, Dana-Farber Cancer Institute.

Boston, Massachusetts, 02115

United States

C.S Mott Children's Hospital

Ann Arbor, Michigan, 48109

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039

United States

Nationwide Children's Hospital

Columbus, Ohio, 43205

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318

United States

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105

United States

University of Texas Southwestern

Dallas, Texas, 75235

United States

Cook Children's Medical Center

Fort Worth, Texas, 76104

United States

Seattle Children's Hospital

Seattle, Washington, 98105

United States

Collaborators and Investigators

Sponsor: New Approaches to Neuroblastoma Therapy Consortium

Keri Streby, MD, STUDY_CHAIR, Nationwide Children's Hospital
Mark Ranalli, MD, STUDY_CHAIR, Nationwide Children's Hospital

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12-16

Study Completion Date2038-12

Study Record Updates

Study Start Date2024-12-16

Study Completion Date2038-12

Terms related to this study

Keywords Provided by Researchers

Relapsed Neuroblastoma
Refractory Neuroblastoma
Cellular Therapy
Immunotherapy
Chemoimmunotherapy

Additional Relevant MeSH Terms

Neuroblastoma