High-risk Neuroblastoma, Refractory Neuroblastoma, Relapsed Neuroblastoma
Conditions
Keywords
Relapsed Neuroblastoma, Refractory Neuroblastoma, High-Risk Neuroblastoma
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.
Interventions
BIOLOGICALAutologous hALK.CAR T cells
Autologous chimeric antigen receptor T cells targeting the human Anaplastic Lymphoma Kinase (ALK) receptor
Sponsors
Boston Children's Hospital
Dana-Farber Cancer Institute
Roberto Chiarle
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Months to 29 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Determine the Maximum Tolerated Dose (MTD) of hALK.CAR T cells | 5 years | 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. |
| Phase 1: Evaluate Manufacturing Feasibility of hALK.CAR T cells | 5 years | 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. |
| Phase 2: Estimate Response Rates | Up to 5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1: Estimate Response Rates | 5 years | 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. |
| Estimate Progression Free Survival and Overall Survival | 5 years | 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. |
| Evaluate Patient-Reported Symptoms | Up to 5 years | 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 |
| Persistence of hALK.CAR T cells | Up to 5 years | 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. |
| Cytokine levels in the peripheral blood | 5 years | Activity of hALK.CAR T cells will be assessed by measuring cytokine levels in the peripheral blood over time |
Countries
United States
Contacts
Primary ContactSusanne Baumeister, MD
Backup ContactAudra Caine
Outcome results
None listed