Immunotherapy of Relapsed Refractory Neuroblastoma With Expanded NK Cells

NCT02573896 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: NANT 2013-01
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 11

Brief Summary

This NANT trial will determine the maximum tolerated dose (MTD) of autologous expanded natural killer (NK) cells when combined with standard dosing of dinutuximab and will assess the feasibility of adding lenalidomide at the recommended Phase II dose of the expanded NK cells with dinutuximab, for treatment of children with refractory or recurrent neuroblastoma.

Conditions

Neuroblastoma

Keywords

relapsed refractory neuroblastoma

Outcome Measures

Primary Outcomes (3)

• NK cell production feasibility (lowest dose level)

  Proportion of patients whose NK cell product is at least 80% of 10\^7 NK cells per kg (sufficient cells to give at least 1 dose at the lowest dose level).

  After cell expansion, day 4 of protocol therapy

• NK cell production feasibility

  Proportion of patients whose NK cell product is at least 80% of the planned dose for one dose

  After cell expansion, day 4 of protocol therapy

• MTD/RP2D determination

  Proportion of patients with any Grade 3 or greater non-hematological toxicities on any course

  all toxicities from enrollment through 30 days following end of protocol therapy

Secondary Outcomes (3)

• Describe Non-Hematological Toxicities

  all toxicities from enrollment through 30 days following end of protocol therapy

• Describe Hematological Toxicities

  all toxicities from enrollment through 30 days following end of protocol therapy

• Overall Response

  From Day 1 of protocol therapy through 30 days following end of protocol therapy

Study Arms (1)

NK cells with Dinutuximab & Lenalidomide

EXPERIMENTAL

Patients in this arm will receive a designated dose of NK cells on Day 5 and 17.5 mg/m2/dose of dinutuximab on Day 1-4. Patients on Dose Level 4 will also receive 25mg/m2/dose of Lenalidomide during Day -6 through 14 of treatment.

Drug: Dinutuximab; Biological: NK Cells; Drug: Lenalidomide

Interventions

Dinutuximab DRUG

17.5 mg/m2/day of dinutuximab will be given for 4 consecutive days (days 1-4 of each course) via intravenous infusion over ten hours.

Also known as: Chimeric Monoclonal Antibody 14.18, MAB Ch 14.18, Unituxin

NK cells with Dinutuximab & Lenalidomide

NK Cells BIOLOGICAL

The designated dose of NK Cells will be infused on Day 5 by IV drip using a Y infusion set with a filter-less chamber. Cells should not be delivered at a rate faster than 10 ml/kg/hr (as determined by drip rate or syringe push rate), and should not take longer than one hour for total infusion time if possible.

Also known as: Natural Killer Cells

NK cells with Dinutuximab & Lenalidomide

Lenalidomide DRUG

25 mg/m2/day of Lenalidomide will be given at Dose Level 4, once daily with or without food by mouth on days -6 through +14.

NK cells with Dinutuximab & Lenalidomide

Eligibility Criteria

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

You may qualify if:

• Patients must be less than or equal to 30 years of age when registered on 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 a history of 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.
• All patients must have at least one of the following
• a) Recurrent/progressive disease: after the diagnosis of high risk neuroblastoma at any time prior to enrollment regardless of response to frontline therapy b) No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma b1) Refractory disease- a best overall response of no response/stable disease since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
• b2) Persistent disease- a best overall response of no partial response since diagnosis of high risk neuroblastoma and at least 4 cycles of induction therapy. No prior history of recurrent/progressive disease since the diagnosis of high risk neuroblastoma.
• 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):
• For recurrent/progressive or refractory disease, at least one MIBG avid bone site.
• For persistent disease, if a patient has 3 or more MIBG avid lesions, then no biopsy is required. If a patients has only 1 or 2 MIBG avid bone lesion sites then biopsy confirmation of neuroblastoma or ganglioneuroblastoma in at least one MIBG avid site present at the time of enrollment is required to be obtained at any time point prior to enrollment.
• For MIBG non-avid tumors, patients must have at least one FDG avid site and a biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma at any time prior to enrollment from at least one FDG-avid site.
• Any amount of neuroblastoma tumor cells in the bone marrow done at the time of study enrollment based on routine morphology with or without immunocytochemistry in at least one sample from bilateral aspirates and biopsies.
• At least one soft tissue lesion that meets criteria for a TARGET lesion as defined by:
• SIZE: Lesion can be accurately measured in at least one dimension with a longest diameter ≥ 10 mm, or for lymph nodes ≥ 15 mm on short axis. Lesions meeting size criteria will be considered measurable.
• In addition to size, a lesion needs to meet one of the following criteria except for patients with parenchymal CNS lesions which only need to meet size criteria:
• b1) MIBG avid. For patients with recurrent/progressive or refractory disease, no biopsy is required. For patients with persistent disease only: If a patient has only 1 or 2 MIBG avid lesions sites, then biopsy confirmation of neuroblastoma and/or ganglioneuroblastoma in at least one MIBG avid site present at time of enrollment is required to be obtained. If a patient has 3 or more MIBG avid lesions, then no biopsy is required.

You may not qualify if:

• Pregnancy: Quantitative Serum B-HCG must be negative in girls who are post-menarchal.
• Breast feeding women are not eligible.
• Active or uncontrolled infection
• CNS metastasis.
• Hypersensitivity to thalidomide, including history of erythema nodosum if characterized by a desquamating rash while taking thalidomide or similar drugs (dose level 4 only).
• Patient declines participation in NANT 2004-05; unless the institution has been granted special exemption from mandatory registration on NANT 2004-05 by the NANT Operations Center.

Sponsors & Collaborators

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

Study Sites (11)

Children's Hospital Los Angeles

Los Angeles, California, 90027-0700, United States

Location

UCSF Helen Diller Family Comprehensive Cancer Center

San Francisco, California, 94115, United States

Location

AFLAC Cancer Center and Blood Disorders Service of Children's Healthcare of Atlanta - Egleston Campus

Atlanta, Georgia, 30322, United States

Location

University of Chicago Comer Children's Hospital

Chicago, Illinois, 60637, 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

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Cook Children's Healthcare System

Fort Worth, Texas, 76104, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

dinutuximab; IL32 protein, human; Lenalidomide

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Officials

• Araz Marachelian, MD, MS

  Children's Hospital Los Angeles

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2015
• First Posted: October 12, 2015
• Study Start: January 14, 2019
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: March 23, 2026

Record last verified: 2026-03

Locations

US (11)