Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma

NCT06803875 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 24-392
• Study Type: interventional
• Target: 42
• Locations: 1 country
• Sites: 2

Brief Summary

This Phase 1/2 trial aims to determine the safety and feasibility of administration of autologous chimeric antigen receptor (CAR) T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor in pediatric subjects with relapsed or refractory neuroblastoma (NB). The trial will be conducted in two phases: Phase 1 will determine the maximum tolerated dose (MTD) of autologous hALK.CAR T cells using a 3+3 dose escalation design. Phase 2 will be an expansion phase to determine rates of response to hALK.CAR T cells.

Conditions

Relapsed Neuroblastoma; Refractory Neuroblastoma; High-risk Neuroblastoma

Keywords

Relapsed Neuroblastoma; Refractory Neuroblastoma; High-Risk Neuroblastoma

Outcome Measures

Primary Outcomes (3)

• Phase 1: Determine the Maximum Tolerated Dose (MTD) of hALK.CAR T cells

  The Maximum Tolerated Dose (MTD) of hALK.CAR T cells will be determined by measuring the incidence of dose limiting toxicities (DLT) following administration of the hALK.CAR T cell product using a 3+3 dose escalation design.

  5 years

• Phase 1: Evaluate Manufacturing Feasibility of hALK.CAR T cells

  Manufacturing feasibility will be evaluated as the proportion of patients undergoing leukapheresis who achieve manufacturing of a hALK.CAR T cell product that meets release criteria.

  5 years

• Phase 2: Estimate Response Rates

  The complete response (CR) and partial response (PR) rates per revised International Neuroblastoma Response Criteria (INRC) of subjects with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells will be estimated.

  Up to 5 years

Secondary Outcomes (5)

• Phase 1: Estimate Response Rates

  5 years

• Estimate Progression Free Survival and Overall Survival

  5 years

• Evaluate Patient-Reported Symptoms

  Up to 5 years

• Persistence of hALK.CAR T cells

  Up to 5 years

• Cytokine levels in the peripheral blood

  5 years

Study Arms (1)

Phase 1 Dose Escalation

EXPERIMENTAL

The dose escalation arm will determine the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of hALK.CAR T cells using a standard 3+3 dose escalation design.

Biological: Autologous hALK.CAR T cells

Interventions

Autologous hALK.CAR T cells BIOLOGICAL

Autologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor

Phase 1 Dose Escalation

Eligibility Criteria

• Age: 12 Months - 29 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Age ≥ 12 months and \< 30 years at the time of consent. The first patient on each dose level will need to be age ≥ 6 years old
• Disease Status:
• Patients must have histologic verification of neuroblastoma at diagnosis or at relapse
• Patients must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at time of study enrollment
• Patients must have persistent/refractory or relapsed disease for which standard curative measures are no longer effective, as defined in the protocol
• Patients must have evaluable or measurable disease per the revised International Neuroblastoma Response Criteria (INRC)
• Adequate washout from prior treatment regimens
• Adequate organ function
• Adequate performance status defined as Lansky or Karnofsky performance score ≥50%
• Subjects of reproductive potential must agree to use acceptable birth control methods
• Signed informed consent

You may not qualify if:

• Pregnant or nursing (lactating) women
• Patients with uncontrolled active infection
• Patients who are concurrently receiving other investigational agents
• Patients who have received prior CART-cell or other gene-modified immune-effector cell therapy, are not eligible unless they are \>8 weeks from time of infusion, have fully recovered from any associated toxicities and have documented lack of persistence of the product
• Patients with a known additional malignancy other than non-melanomatous skin cancer or carcinoma in situ, unless not requiring active treatment and stable or disease-free for at least 3 years
• Uncontrolled CNS metastasis
• CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement which may impair the ability to evaluate neurotoxicity
• History of severe hypersensitivity reaction to compounds used in the study
• HIV/HBV/HCV infection
• Patients receiving systemic steroid therapy (physiologic replacement, inhaled steroids and premedication for blood products are allowed)
• Primary immunodeficiency or history of systemic autoimmune disease requiring systemic immunosuppression/disease modifying agents within the last 2 years
• Uncontrolled intercurrent illness
• Inability to comply with the study requirements

Sponsors & Collaborators

• Roberto Chiarle: lead
• Boston Children's Hospital: collaborator
• Dana-Farber Cancer Institute: collaborator

Study Sites (2)

Boston Children's Hospital

Boston, Massachusetts, 02115, United States

RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

RECRUITING

Related Publications (1)

• Bergaggio E, Tai WT, Aroldi A, Mecca C, Landoni E, Nuesch M, Mota I, Metovic J, Molinaro L, Ma L, Alvarado D, Ambrogio C, Voena C, Blasco RB, Li T, Klein D, Irvine DJ, Papotti M, Savoldo B, Dotti G, Chiarle R. ALK inhibitors increase ALK expression and sensitize neuroblastoma cells to ALK.CAR-T cells. Cancer Cell. 2023 Dec 11;41(12):2100-2116.e10. doi: 10.1016/j.ccell.2023.11.004. Epub 2023 Nov 30.

  PMID: 38039964 BACKGROUND

MeSH Terms

Conditions

Neuroblastoma

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

Study Officials

• Susanne Baumeister, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Susanne Baumeister, MD

CONTACT

617-632-3796; dfbchpedicelltherapy@dfci.harvard.edu

Audra Caine

CONTACT

617-632-3796; audra_caine@dfci.harvard.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor in Pathology

Study Record Dates

• First Submitted: September 16, 2024
• First Posted: January 31, 2025
• Study Start: January 31, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029
• Last Updated: December 26, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data can be shared no earlier than 1 year following the date of publication
• Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu

Locations

US (2)