Clinical trial NCT06803875: Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma
Official title: A Phase 1/2 Study of hALK.CAR T Cells for Patients With Relapsed/Refractory High-risk Neuroblastoma
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Relapsed Neuroblastoma
Refractory Neuroblastoma
High-risk Neuroblastoma
Keywords: Relapsed Neuroblastoma
Refractory Neuroblastoma
High-Risk Neuroblastoma
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: Boston Children's Hospital
name: Dana-Farber Cancer Institute
First posted: 2025-01-31
Enrollment: 42
Sex: ALL
Minimum age (years): 12
Maximum age (years): 29
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Phase 1: Determine the Maximum Tolerated Dose (MTD) of hALK.CAR T cells
timeFrame: 5 years
measure: Phase 1: Evaluate Manufacturing Feasibility of hALK.CAR T cells
timeFrame: 5 years
measure: Phase 2: Estimate Response Rates
timeFrame: Up to 5 years
Secondary outcomes:
measure: Phase 1: Estimate Response Rates
timeFrame: 5 years
measure: Estimate Progression Free Survival and Overall Survival
timeFrame: 5 years
measure: Evaluate Patient-Reported Symptoms
timeFrame: Up to 5 years
measure: Persistence of hALK.CAR T cells
timeFrame: Up to 5 years
measure: Cytokine levels in the peripheral blood
timeFrame: 5 years
Other outcomes:
Locations:
city: Boston
country: United States
facility: Boston Children's Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
Study officials:
affiliation: Dana-Farber Cancer Institute
name: Susanne Baumeister, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.