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

A Phase 1/2 Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma

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.

Study Overview

• Status: Recruiting
• Conditions: Refractory Neuroblastoma; High-risk Neuroblastoma; Relapsed Neuroblastoma
• Intervention / Treatment: Biological: Autologous hALK.CAR T cells

Detailed Description

This study consists of two phases. The primary objectives of Phase 1 and Phase 2 are:

Phase 1:

• To identify the maximum tolerated dose (MTD) of autologous hALK.CAR T cells, and the recommended phase 2 dose (RP2D) in participants with relapsed/refractory high-risk neuroblastoma.
• To evaluate the feasibility of manufacturing autologous hALK.CAR T cells.

Phase 2:

To estimate the complete response (CR) and partial response (PR) rates per revised International Neuroblastoma Response Criteria (INRC) of participants with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Susanne Baumeister, MD; Phone Number: 617-632-3796; Email: dfbchpedicelltherapy@dfci.harvard.edu
• Study Contact Backup: Name: Audra Caine; Phone Number: 617-632-3796; Email: audra_caine@dfci.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Boston Children's Hospital
      • Principal Investigator: Susanne Baumeister, MD
      • Contact: Susanne Baumeister, MD; Phone Number: 617-632-3796; Email: dfbchpedicelltherapy@dfci.harvard.edu
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Susanne Baumeister, MD
      • Contact: Susanne Baumeister, MD; Phone Number: 617-632-3796; Email: dfbchpedicelltherapy@dfci.harvard.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. 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

2. Disease Status:

   1. Patients must have histologic verification of neuroblastoma at diagnosis or at relapse
   2. Patients must have high-risk neuroblastoma according to Children's Oncology Group (COG) risk classification at time of study enrollment
   3. Patients must have persistent/refractory or relapsed disease for which standard curative measures are no longer effective, as defined in the protocol
   4. Patients must have evaluable or measurable disease per the revised International Neuroblastoma Response Criteria (INRC)
3. Adequate washout from prior treatment regimens
4. Adequate organ function
5. Adequate performance status defined as Lansky or Karnofsky performance score ≥50%
6. Subjects of reproductive potential must agree to use acceptable birth control methods
7. Signed informed consent

Exclusion Criteria:

1. Pregnant or nursing (lactating) women
2. Patients with uncontrolled active infection
3. Patients who are concurrently receiving other investigational agents
4. 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
5. 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
6. Uncontrolled CNS metastasis
7. CNS disorder such as cerebrovascular ischemia/hemorrhage, dementia, cerebellar disease, or autoimmune disease with CNS involvement which may impair the ability to evaluate neurotoxicity
8. History of severe hypersensitivity reaction to compounds used in the study
9. HIV/HBV/HCV infection
10. Patients receiving systemic steroid therapy (physiologic replacement, inhaled steroids and premedication for blood products are allowed)
11. Primary immunodeficiency or history of systemic autoimmune disease requiring systemic immunosuppression/disease modifying agents within the last 2 years
12. Uncontrolled intercurrent illness
13. Inability to comply with the study requirements

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Dose Escalation; 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; Autologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: 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 in the Phase 1 cohort will be estimated.	5 years
Estimate Progression Free Survival and Overall Survival	To estimate the progression free survival (PFS) and overall survival (OS) rates of subjects with relapsed or refractory high-risk neuroblastoma who are treated with hALK.CAR T cells.	5 years
Evaluate Patient-Reported Symptoms	Patient-reported symptoms of interest (including mood, gastrointestinal and pain symptoms) will be measured in subjects treated with hALK.CAR T cells using the Ped-PRO-CTCAE v.1 inventory prior to and until 2 years after hALK.CAR T cell infusion	Up to 5 years
Persistence of hALK.CAR T cells	Persistence of hALK.CAR T cells will be measured by Polymerase Chain Reaction (or flow cytometry) analysis to detect and quantify survival of hALK.CAR T cells in the peripheral blood over time.	Up to 5 years
Cytokine levels in the peripheral blood	Activity of hALK.CAR T cells will be assessed by measuring cytokine levels in the peripheral blood over time	5 years

Collaborators and Investigators

• Sponsor: Roberto Chiarle
• Collaborators: Dana-Farber Cancer Institute; Boston Children's Hospital
• Investigators: Principal Investigator: Susanne Baumeister, MD, Dana-Farber Cancer Institute

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 31, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2029

Study Registration Dates

• First Submitted: September 16, 2024
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): January 31, 2025

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 24, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Refractory Neuroblastoma; Relapsed Neuroblastoma; High-Risk Neuroblastoma
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Neuroectodermal Tumors, Primitive, Peripheral; Neuroectodermal Tumors, Primitive; Neuroblastoma
• Other Study ID Numbers: 24-392

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: roberto.chiarle@childrens.harvard.edu. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Belfer Office for Dana-Farber Innovations (BODFI) at innovation@dfci.harvard.edu
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No