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

NCT06450041 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NANT 2021-01
• Study Type: interventional
• Target: 62
• Locations: 1 country
• Sites: 13

Brief Summary

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

Conditions

Neuroblastoma

Keywords

Relapsed Neuroblastoma; Refractory Neuroblastoma; Cellular Therapy; Immunotherapy; Chemoimmunotherapy

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rate of Evaluable Patients

  The response evaluation is based on central review or site review (when central review is not available) of patient diagnostic assessments. Response is determined by the NANT response criteria v2.0 (https://doi.org/10.1002/pbc.26940). 1. Complete response 2. Partial response 3. Minor response 4. Stable response 5. Progressive disease 6. Early death from malignant disease 7. Early death from toxicity Evaluable response patients have received sufficient therapy (1) and have sufficient response evaluation data to assess best overall response (2) including patients in categories f and g 1. is defined as at least 75% of all therapeutic agents in course 1, or less than 75% in course 1 due to clinical signs of tumor progression or therapy related toxicity. 2. is defined as presence of a disease evaluation for each of the 3 disease parameters (bone, soft tissue, bone marrow) at one or more timepoints after enrollment. Best Overall Response Rate = (a+b+c)/ (a+b+c+d+e+f+g).

  Baseline assessments from within 28 days before Day 1 on study and between days 12-24 of cycles 2, 4, and 6, and within two weeks after the last date of protocol therapy. Each cycle will be 21 days but may be extended to 28 days due to treatment delays.

Secondary Outcomes (2)

• Proportion of Evaluable Participants with Grade 3 or Greater Hematologic Toxicities or Any Hematologic Toxicities Attributed to this therapy.

  All toxicities from enrollment through 30 days following end of protocol therapy, an average of 6 months

• Proportion of Evaluable of Participants with Grade 2 or Greater Non-Hematologic Toxicities or Any Non-Hematologic Toxicities Attributed to this therapy.

  All toxicities from enrollment through 30 days following end of protocol therapy, an average of 6 months

Study Arms (1)

Treatment

EXPERIMENTAL

Patients will be treated with chemoimmunotherapy (temozolomide, irinotecan, GM-CSF, and dinutuximab) plus UD TGFβi NK cells.

Drug: Universal Donor (UD) TGFβi NK Cells; Drug: Temozolomide; Drug: Irinotecan; Drug: Dinutuximab; Drug: GM-CSF

Interventions

Temozolomide DRUG

Enteral or IV daily on days 1-5 of each cycle For patients ≥ 0.5 m2: 100 mg/m2/dose For patients \< 0.5 m2: 3.3 mg/kg/dose MAXIMUM dose = 200 mg

Treatment

Irinotecan DRUG

50mg/m2/dose IV daily on days 1-5 of each cycle

Treatment

Dinutuximab DRUG

17.5mg/m2/dose IV daily on days 2-5 of each cycle

Also known as: Unituxin

Treatment

GM-CSF DRUG

250mcg/m2/dose subcutaneous (preferred) or IV daily on days 6-12 of each cycle

Also known as: Sargramostim

Treatment

Universal Donor (UD) TGFβi NK Cells DRUG

Patients will receive a dose of 1x108 UD TGFβi NK cells/kg per treatment cycle on day 8 of each cycle

Treatment

Eligibility Criteria

• Age: 1 Year - 31 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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:
• \) Recurrent/progressive disease after the diagnosis of high risk neuroblastoma at any time prior to enrollment - regardless of response to frontline therapy. (Note that this excludes patients initially considered low or intermediate risk that progressed to high risk disease but have not progressed after the diagnosis of high risk neuroblastoma).
• \) If no prior history of recurrent/progressive disease since the diagnosis of high-risk neuroblastoma,
• a) Refractory disease: A best overall response of no response/stable disease since diagnosis of high-risk neuroblastoma AND after at least 4 courses of induction therapy.
• b) Persistent disease: A best overall response of partial response since diagnosis of high-risk neuroblastoma AND after at least 4 courses of induction therapy
• 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:
• \) Bone Sites
• a) MIBG avid tumors: patients must meet one of the following criteria:
• a. Patients with recurrent/progressive or refractory disease: i. Must have at least one MIBG avid bone site on planar imaging OR ii. Must have \> 2 avid bone lesions on SPECT. iii. A biopsy is not required unless the above imaging criteria are not met. b. Patients with persistent disease: i. If a patient has 3 or more MIBG avid sites by planar or SPECT imaging (including soft tissue and/or bone), then no biopsy is required.
• ii. If a patient has only 1 or 2 MIBG avid sites by planar or SPECT imaging (including soft tissue and/or bone) then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment is required. Bone lesions may be biopsied at any time point prior to enrollment.
• b) For MIBG non-avid tumors, patients must have biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma from a lesion at any time prior to enrollment of at least one site (with or without FDG-PET uptake).
• \) Bone Marrow Any amount of tumor cells in the bone marrow (including neuroblasts, mature and maturing ganglion cells) done at the time of study enrollment based on routine morphology and/or immunohistochemistry in at least one sample from bilateral aspirates and biopsies.

You may not qualify if:

• 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.
• Note: Exceptions are the following:

Sponsors & Collaborators

• Nationwide Children's Hospital: collaborator
• United Therapeutics: collaborator
• Children's Neuroblastoma Cancer Fund: collaborator
• New Approaches to Neuroblastoma Therapy Consortium: lead

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

RECRUITING

UCSF Benioff Children's Hospital

San Francisco, California, 94143, United States

NOT YET RECRUITING

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Comer Children's Hospital, University of Chicago

Chicago, Illinois, 60614, United States

NOT YET RECRUITING

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

Boston, Massachusetts, 02115, United States

NOT YET RECRUITING

C.S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

NOT YET RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

NOT YET RECRUITING

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

RECRUITING

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

RECRUITING

University of Texas Southwestern

Dallas, Texas, 75235, United States

RECRUITING

Cook Children's Medical Center

Fort Worth, Texas, 76104, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, 98105, United States

NOT YET RECRUITING

MeSH Terms

Conditions

Neuroblastoma

Interventions

Temozolomide; Irinotecan; dinutuximab; Granulocyte-Macrophage Colony-Stimulating Factor; sargramostim

Condition Hierarchy (Ancestors)

Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Camptothecin; Alkaloids; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Keri Streby, MD

  Nationwide Children's Hospital

  STUDY CHAIR

• Mark Ranalli, MD

  Nationwide Children's Hospital

  STUDY CHAIR

Central Study Contacts

Araz Marachelian, MD

CONTACT

3233615687; nantops@chla.usc.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 31, 2024
• First Posted: June 10, 2024
• Study Start: December 16, 2024
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2038
• Last Updated: June 10, 2026

Record last verified: 2026-03

Locations

US (13)