Allogeneic Tumor Cell Vaccination With Oral Metronomic Cytoxan in Patients With High-Risk Neuroblastoma

NCT01192555 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: H-26652-ATOMIC
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

Neuroblastoma is the second most common solid tumor seen in children, but causes approximately 15% of childhood cancer deaths each year. Patients with high-risk disease require treatment with a combination of chemotherapy, surgery, radiation, and stem cell transplant; however, many will have their disease come back within 3 years. Due to this high rate of relapse, this study is being done to investigate an experimental treatment option for children whose disease has returned. This clinical trial is for patients with neuroblastoma that has either come back after treatment or never went away in the first place. A series of immunizations will be administered using a tumor vaccine and add low-dose chemotherapy to be taken by mouth on a daily basis. The hope is that the vaccine will cause the immune system to recognize and kill more types of neuroblastoma tumors. Additionally, the immunizations will be combined with daily low dose chemotherapy. Daily low-dose chemotherapy, also know as metronomic chemotherapy, works by attacking the blood vessels that allow tumors to grow. Using metronomic doses of a drug called cytoxan can also decrease T regulatory cells, a specific type of cell that tumors use to hide from the immune system. The purpose of this study is to test the safety and anti-tumor effect of the tumor cell vaccination plus low dose, metronomic chemotherapy in treating patients with relapsed/refractory neuroblastoma.

Conditions

Neuroblastoma

Keywords

Neuroblastoma; Chemotherapy; Pediatrics; Cytoxan; immunotherapy; vaccine

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Phase I Primary Objective: Evaluate the safety of fixed dose oral cytoxan administered metronomically to coincide with repeated immunizations of gene-modified, IL-2/lymphotactin secreting SJNB-JF-IL2 and SJNB-JF-LTN cells co-administered with unmodified SKNLP neuroblastoma cell lines in patients with a history of relapsed/refractory high-risk neuroblastoma.

  week 30

Secondary Outcomes (2)

• Participants with T-cell changes as a Measure of Immune Response

  15 years

• Number of Participants with Disease Progression as a Measure of Efficacy

  10 weeks

Other Outcomes (1)

• Analysis of Immunologic Measurements

  15 years

Study Arms (1)

Treatment Plan

EXPERIMENTAL

Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells) and Cytoxan (Cyclophosphamide)

Biological: Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells; Drug: Cytoxan

Interventions

Neuroblastoma Vaccine (unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells BIOLOGICAL

1x10\^7cells/m2 each of unmodified SKNLP, with gene-modified SJNB-JF-IL2 and SJNB-JF-LTN neuroblastoma cells will be given by subcutaneous injection while suspended in Ringers solution with 5% HSA in a single syringe in a volume of up to 1 ml. Vaccines will be given on day 0 of week 0 and then on day 0 (+ 72 hours) of weeks 2, 4, 6, 9, 12, 16, 20. Cells will be administered as a subcutaneous injection over 1 minute using a 21-gauge needle. Procedural pain control methods may be used per institutional protocol.

Also known as: SKNLP w/ gene-mod. SJNB-JF-IL2 & SJNB-JF-LTN neurobl. cells

Treatment Plan

Cytoxan DRUG

Metronomic oral cytoxan will start 72 hours prior to the first vaccination at a dose of 50 mg/m2/day. Cytoxan will be held on the day of vaccine administration and for the next 96 hours. After the first vaccine, patients will take 25 mg/m2/day as outlined on the roadmap.

Also known as: Cyclophosphamide

Treatment Plan

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Histologically proven high risk neuroblastoma in first or subsequent relapse or with primary refractory disease or inability to complete standard therapy
• Age less than 21 at time of initial diagnosis
• Life expectancy 12 weeks or greater
• Karnofsky or Lansky score of 50 or greater
• Platelet count of 50,000/ul or greater
• ANC greater than 750/ul
• Alk Phos level less than 2.5 x upper limit of normal
• Bilirubin less than 2x normal
• AST less than 3x normal
• Hgb 8.0 or greater
• Creatinine 2 x ULN or less OR GFR greater than 40 ml/min/1.73 m2
• Patient has recovered from last chemotherapy or investigational therapy prior to study enrollment
• Women of child-bearing potential must not be pregnant and take/use effective birth control while participating in the study.

You may not qualify if:

• Due to the unknown effects of this therapy on a fetus, pregnant women will be excluded from this research
• Women who are breast-feeding
• Known HIV positive subjects since treatment may be immunosuppressive
• Severe intercurrent infection or uncontrolled condition including, but not limited to ongoing or active infection, symptomatic heart failure, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Previous use of oral cytoxan for more than 2 consecutive months within the last 6 months
• Patients currently receiving any investigational agents or have received any tumor vaccines within the previous six months
• Patients, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study

Sponsors & Collaborators

• Baylor College of Medicine: lead
• Center for Cell and Gene Therapy, Baylor College of Medicine: collaborator

Study Sites (1)

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Neuroblastoma

Interventions

Cyclophosphamide

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

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Malcolm Brenner, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: August 16, 2010
• First Posted: September 1, 2010
• Study Start: September 1, 2010
• Primary Completion: July 1, 2012
• Study Completion (Estimated): September 1, 2026
• Last Updated: August 1, 2025

Record last verified: 2025-07

Locations

US (1)