RECRUITING

Allogeneic Expanded Gamma Delta T Cells With GD2 Chemoimmunotherapy in Relapsed /Refractory Neuroblastoma or Refractory/ Relapsed Osteosarcoma

Conditions

Neuroblastoma Refractory Neuroblastoma Relapsed Neuroblastoma Relapsed Osteosarcoma Refractory Osteosarcoma Gamma Delta T Cells Dinutuximab Temozolomide Zoledronate Irinotecan GD2 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

The goal of this clinical trial is to determine the maximum tolerated dose (MTD) and recommended Phase II dose (RP2D) of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate in children with refractory or recurrent neuroblastoma or refractory/ relapsed osteosarcoma as well as to define the toxicities of allogeneic expanded γδ T cells when delivered with Dinutuximab, temozolomide, irinotecan, and zoledronate

Official Title

A Phase I Study of Allogeneic Ex Vivo Expanded Gamma Delta (γδ) T Cells in Combination With Dinutuximab, Temozolomide, Irinotecan, and Zoledronate in Children With Refractory/ Relapsed, or Progressive Neuroblastoma or Refractory/ Relapsed Osteosarcoma

Quick Facts

Study Start:2023-11-06

Study Completion:2025-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05400603

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:12 Months

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Patients must be ≥ 12 months of age at the time of enrollment in the study. * Diagnosis: Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. (Bone marrow samples with positive catecholamines are acceptable as confirmation of neuroblastoma) OR histological confirmation of osteosarcoma at diagnosis * Response to prior therapy: * High-risk neuroblastoma with refractory, relapsed or progressive disease, defined as: * First or greater relapse of neuroblastoma following completion of aggressive multi- drug frontline therapy. * First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy. * Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) after at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532). * Note that this excludes patients initially considered low or intermediate-risk neuroblastoma that progressed to high-risk disease but the patient has not progressed after the diagnosis of high-risk neuroblastoma. * Relapsed or refractory osteosarcoma that is not responsive to standard treatment * Disease Status * Patients must have measurable or evaluable disease per revised INRC for subjects with neuroblastoma or measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with Osteosarcoma * Performance Level:Patients must have a Lansky (≤16 years) or Karnofsky (\>16 years) score of ≥50 * Prior Therapy * Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before study registration. * Prior dinutuximab therapy is allowed regardless of prior response or progression on dinutuximab * Prior temozolomide therapy is allowed * Prior zoledronate is allowed * Prior dinutuximab/temozolomide/irinotecan chemoimmunotherapy is allowed * Prior T cell therapy is excluded * Organ Function Requirements: * Hematologic Functions : Absolute Neutrofil count ≥750/uL and platelet count ≥ 75,000/µl, transfusion independent . * Renal Function: 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 serum glutamic-pyruvic transaminase (SGPT) (ALT) ≤ 135 U/L (≤ 3x ULN). * Cardiac Function: Normal ejection fraction (≥ 55%) documented by either echocardiogram or radionuclide multigated acquisition scan (MUGA) evaluation OR Normal fractional shortening (≥ 27%) documented by echocardiogram * Pulmonary Function: Normal pulmonary function with no evidence of dyspnea at rest, no exercise intolerance.	* Prior T cell therapy * Pregnancy, breast feeding, or unwillingness to use effective contraception during the study will not be entered on this 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 known active Central Nervous System (CNS) disease (excluding skull disease with intracranial extension). Patients with a history of CNS disease are required to have a brain CT and/ or MRI at study registration. * Patients with prior allogeneic stem cell 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 * 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 with disease of any major organ system that would compromise their ability to withstand therapy. * Patients who have had to permanently discontinue Dinutuximab due to toxicity * Patients with serious, uncontrolled cardiac arrhythmias * Patients with a history of myocarditis * Patients who have received any live vaccines within 30 days before enrollment

Inclusion Criteria

Exclusion Criteria

* Patients must be ≥ 12 months of age at the time of enrollment in the study.
* Diagnosis: Histological confirmation of neuroblastoma or ganglioneuroblastoma at initial diagnosis. (Bone marrow samples with positive catecholamines are acceptable as confirmation of neuroblastoma) OR histological confirmation of osteosarcoma at diagnosis
* Response to prior therapy:
* High-risk neuroblastoma with refractory, relapsed or progressive disease, defined as:
* First or greater relapse of neuroblastoma following completion of aggressive multi- drug frontline therapy.
* First episode of progressive neuroblastoma during aggressive multi-drug frontline therapy.
* Persistent/refractory neuroblastoma as defined by less than a complete response by the revised International Neuroblastoma Response Criteria (INRC) after at least 4 cycles of aggressive multidrug induction chemotherapy on or according to a high-risk neuroblastoma protocol (such as A3973 or ANBL0532).
* Note that this excludes patients initially considered low or intermediate-risk neuroblastoma that progressed to high-risk disease but the patient has not progressed after the diagnosis of high-risk neuroblastoma.
* Relapsed or refractory osteosarcoma that is not responsive to standard treatment
* Disease Status
* Patients must have measurable or evaluable disease per revised INRC for subjects with neuroblastoma or measurable or evaluable disease by Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 for subjects with Osteosarcoma
* Performance Level:Patients must have a Lansky (≤16 years) or Karnofsky (\>16 years) score of ≥50
* Prior Therapy
* Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy before study registration.
* Prior dinutuximab therapy is allowed regardless of prior response or progression on dinutuximab
* Prior temozolomide therapy is allowed
* Prior zoledronate is allowed
* Prior dinutuximab/temozolomide/irinotecan chemoimmunotherapy is allowed
* Prior T cell therapy is excluded
* Organ Function Requirements:
* Hematologic Functions : Absolute Neutrofil count ≥750/uL and platelet count ≥ 75,000/µl, transfusion independent .
* Renal Function: 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 serum glutamic-pyruvic transaminase (SGPT) (ALT) ≤ 135 U/L (≤ 3x ULN).
* Cardiac Function: Normal ejection fraction (≥ 55%) documented by either echocardiogram or radionuclide multigated acquisition scan (MUGA) evaluation OR Normal fractional shortening (≥ 27%) documented by echocardiogram
* Pulmonary Function: Normal pulmonary function with no evidence of dyspnea at rest, no exercise intolerance.

* Prior T cell therapy
* Pregnancy, breast feeding, or unwillingness to use effective contraception during the study will not be entered on this 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 known active Central Nervous System (CNS) disease (excluding skull disease with intracranial extension). Patients with a history of CNS disease are required to have a brain CT and/ or MRI at study registration.
* Patients with prior allogeneic stem cell 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
* 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 with disease of any major organ system that would compromise their ability to withstand therapy.
* Patients who have had to permanently discontinue Dinutuximab due to toxicity
* Patients with serious, uncontrolled cardiac arrhythmias
* Patients with a history of myocarditis
* Patients who have received any live vaccines within 30 days before enrollment

Contacts and Locations

Study Contact

Kelly Goldsmith, MD

CONTACT

(404) 727-2655

kgoldsm@emory.edu; mpactcto@choa.org

Principal Investigator

Kelly Goldsmith, MD

PRINCIPAL_INVESTIGATOR

Profesor

Study Locations (Sites)

Children's Healthcare of Atlanta

Atlanta, Georgia, 30322

United States

Collaborators and Investigators

Sponsor: Emory University

Kelly Goldsmith, MD, PRINCIPAL_INVESTIGATOR, Profesor

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 Date2023-11-06

Study Completion Date2025-12

Study Record Updates

Study Start Date2023-11-06

Study Completion Date2025-12

Terms related to this study

Keywords Provided by Researchers

Gamma Delta T Cells
Dinutuximab
Temozolomide
Zoledronate
Irinotecan
GD2
chemoimmunotherapy

Additional Relevant MeSH Terms

Neuroblastoma
Refractory Neuroblastoma
Relapsed Neuroblastoma
Relapsed Osteosarcoma
Refractory Osteosarcoma