NANT 2021-02: Randomized MIBG With Vorinostat/Dinutuximab/Vorinostat + Dinutuximab

NCT07261241 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: NANT 2021-02
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 13

Brief Summary

Patients will then be randomized at study entry to one of three treatment arms. Patients on Arm A will receive a single treatment course with 131I-MIBG with vorinostat. Patients on Arm B will receive a single treatment course with 131I-MIBG and dinutuximab. Patients on Arm C will receive a single treatment course with 131I-MIBG with dinutuximab + vorinostat. After this course of treatment, we will check to see your response and then check to see how you are doing over time. All patients may choose to proceed to a second course of the same treatment if they and their physician feel healthy enough to do so. Approximately 118 patients will be receiving therapy on this trial.

Conditions

Neuroblastoma

Outcome Measures

Primary Outcomes (1)

• Objective Tumor Response After One Course of Therapy

  To identify the MIBG treatment regimen associated with the highest overall response rate after one course of treatment on the three arms. The response evaluation was based on central review (intent to treat analysis). Responders defined as meeting CR/MRD/PR criteria. Response was based on NANT response criteria v1.2 (https://doi.org/10.1002/pbc.26940). RECST 1.1 criteria was used for measurable tumors with PR criteria \> 30% decrease in target tumor size. Curie score was used with PR criteria \> 50% decrease in Curie score. Complete Response- disappearance of all target lesions, Curie score of 0 and no detectable bone marrow disease. Overall Response (OR)=CR+PR.

  43-50 days from study day 1

Secondary Outcomes (10)

• Number of Participants With Grade 3 or Greater Non-hematologic Toxicities

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

• Objective Tumor Response After Two Courses of Therapy

  43-50 days from study day 1

• Objective Bone Marrow Tumor Response After One Course of Therapy

  43-50 days from study day 1

• Objective Bone Marrow Tumor Response After Two Courses of Therapy

  43-50 days from study day 1

• Objective Soft Tissue Tumor Response After One Course of Therapy

  43-50 days from study day 1

Study Arms (3)

Arm A: 131I-MIBG + vorinostat

EXPERIMENTAL

Patients assigned to Arm A will receive vorinostat orally once daily on Days 0 to 13 at a dose of 180 mg/m2/dose (maximum dose 400 mg). Patients will receive 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1 and autologous stem cell infusion on Day 15 (plus 2 days or minus 1 day, hereafter abbreviated as +2/-1 days). There must be at least 24 hours between the last dose of vorinostat and stem cell infusion. Disease evaluation is to occur between days 50-60. The time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks.

Drug: Radiation: 131I-MIBG; Drug: Vorinostat

Arm B: 131I-MIBG + dinutuximab

EXPERIMENTAL

Patients assigned to Arm B will receive 18 mCi/kg (maximum dose 1200 mCi) 131I-MIBG on Day 1 and autologous stem cell infusion on Day 15 (+2/-1 days). Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy. Disease evaluation is to occur between Days 50-60. In case of treatment delays with dinutuximab during Course 1, the time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks.

Drug: Radiation: 131I-MIBG; Drug: Dinutuximab

Arm C: 131I-MIBG + vorinostat + dinutuximab

EXPERIMENTAL

Patients assigned to Arm C will receive vorinostat 180 mg/m2/dose (maximum dose 400 mg) on Days 0 to 13, 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1. Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy. Disease evaluation is to occur between Days 50-60. In case of treatment delays with dinutuximab during Course 1, the time interval between performing end of Course 1 disease evaluation and administration of Course 2 131I-MIBG is not to exceed 4 weeks.

Drug: Radiation: 131I-MIBG; Drug: Dinutuximab; Drug: Vorinostat

Interventions

Radiation: 131I-MIBG DRUG

Patients will receive 131I-MIBG 18 mCi/kg (maximum dose 1200 mCi) on Day 1

Also known as: Iobenguane I 131

Arm A: 131I-MIBG + vorinostat; Arm B: 131I-MIBG + dinutuximab; Arm C: 131I-MIBG + vorinostat + dinutuximab

Dinutuximab DRUG

Dinutuximab 17.5 mg/m2/day is given intravenously on Days 8-11 and 29-32 of therapy

Also known as: Chimeric Monoclonal Antibody 14.18, Chimeric MOAB 14.18, human/murine anti-GD2 monoclonal antibody, chimeric anti-GD2, chimeric mAb 14.18, ch14.18, Unituxin

Arm B: 131I-MIBG + dinutuximab; Arm C: 131I-MIBG + vorinostat + dinutuximab

Vorinostat DRUG

Vorinostat will be given on days 0-13 at a dose of 180 mg/m2/dose (maximum dose 400 mg).

Also known as: Zolinza

Arm A: 131I-MIBG + vorinostat; Arm C: 131I-MIBG + vorinostat + dinutuximab

Eligibility Criteria

• Age: 1 Year - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age Patients must be ≥ 1 year and \< 30 years of age at the time of study registration.
• Diagnosis Patients must have a diagnosis of neuroblastoma or ganglioneuroblastoma nodular subtype either by histologic verification of neuroblastoma and/or demonstration of tumor cells in the bone marrow with increased urinary catecholamines.
• Disease Risk Group Patients must have high risk neuroblastoma according to COG risk classification at the time of study registration. Patients who were initially considered low or intermediate risk, but then reclassified as high risk are also eligible.
• Response to Prior Therapy (using INRC definitions)
• 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,
• 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.
• Persistent disease: A best overall response of minor response since diagnosis of high risk neuroblastoma AND after at least 4 courses of induction therapy:
• i. If a patient with persistent disease has 3 or more MIBG avid sites (including all soft tissue and/or bone lesions) OR a Curie Score of ≥ 3, then no biopsy is required for eligibility.
• ii. If a patient with persistent disease has only 1 or 2 MIBG avid sites (including all soft tissue and/or bone lesions) then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site (bone marrow, bone, or soft tissue) present at the time of registration is required. Bone and/or soft tissue lesions may be biopsied at any time point prior to study registration, bone marrow must be done at the time of study registration.

You may not qualify if:

• Autologous peripheral blood stem cells (PBSC)
• The minimum dose for peripheral blood stem cells is 1.5 x 106 viable CD34+ cells/kg. Patients who do not meet this minimum requirement for available PBSCs are not eligible.
• Only un-purged stem cells are allowed unless a center has separate FDA approval for infusion of purged stem cells.
• For patients whose body weight exceeds ideal body weight (IBW) by more than 20%, adjusted body weight may be used for the calculation of PBSC dose.47
• Performance level Patients must have a Lansky (≤ 16 years) or Karnofsky (\> 16 years) score of ≥ 50 Note: Subjects 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.
• Prior Therapy Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to study registration.
• Organ Function Requirements
• Hematologic Function:
• Patients must meet the following hematologic criteria for enrollment regardless of bone marrow disease involvement:
• ANC ≥750/uL (no short-acting hematopoietic growth factors ≤ 7 days of blood draw documenting eligibility and no long-acting hematopoietic growth factors ≤ 14 days of blood draw documenting eligibility); and
• Platelet count ≥ 50,0000/µl, transfusion independent (no platelet transfusions or platelet growth factors ≤ 7 days of blood draw documenting eligibility).
• Renal Function a. Patients must have adequate renal function defined as age-adjusted serum creatinine ≤1.5 ULN for age Liver Function
• Total bilirubin ≤ 1.5 x ULN for age; and,
• 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.
• Central Nervous System (CNS) Function:

Sponsors & Collaborators

• New Approaches to Neuroblastoma Therapy Consortium: lead
• United Therapeutics: collaborator
• Jubilant DraxImage Inc.: collaborator

Study Sites (13)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94143, United States

Location

Children Hospital of Colorado

Aurora, Colorado, 80045, United States

Location

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322, United States

Location

Children's Memorial Hospital - Chicago

Chicago, Illinois, 60614, United States

Location

Childrens Hospital Boston, Dana-Farber Cancer Institute.

Boston, Massachusetts, 02115, United States

Location

C.S Mott Children's Hospital

Ann Arbor, Michigan, 48109, United States

Location

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229-3039, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

University of Texas Southwestern

Dallas, Texas, 75235, United States

Location

Cook Children's Medical Center - Fort Worth

Fort Worth, Texas, 76104, United States

Location

Children's Hospital and Regional Medical Center - Seattle

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

3-Iodobenzylguanidine; dinutuximab; Vorinostat

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)

Guanidines; Amidines; Organic Chemicals; Iodobenzenes; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Iodinated; Hydrocarbons, Halogenated; Anilides; Amides; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids

Central Study Contacts

Araz Marachelian, MD

CONTACT

323-361-5687; nantops@chla.usc.edu

Study Design

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

Study Record Dates

• First Submitted: November 21, 2025
• First Posted: December 3, 2025
• Study Start (Estimated): July 31, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2031
• Last Updated: December 3, 2025

Record last verified: 2025-11

Locations

US (13)