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

Phase 1

Active, not recruiting

Conditions: Neuroblastoma

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

Registration Number: NCT01192555

Lead Sponsor: Baylor College of Medicine

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.

Detailed Description: WHAT IS THE OVERALL TREATMENT PLAN AND HOW MANY VACCINATIONS WILL THE PATIENT RECEIVE? There will be several injections of the vaccine scheduled. The first injection will be given 3 days after starting oral cytoxan. The 2nd to 4th injections will be given approximately every 14 days after the previous vaccine. During this time, the patient will be taking oral cytoxan once a day except on the day of and 4 days following the vaccine. Two to 3 weeks after the 4th vaccine, the patient will have a complete evaluation of their disease. If the scans and lab tests show that the patient has not had any serious side-effects, they will be eligible to receive 4 additional vaccinations given at 3 week intervals. The disease will be re-evaluated again after vaccine numbers 6 and 8. If the patient is able to complete the entire study, they will have received a total of 8 vaccinations and the last dose of oral cytoxan will be 1 month after the 8th vaccination. Total time duration for participating in this study is 15 years (treatment portion within year 1 and follow up during years 2-15).

Neuroblastoma vaccinations are given like many other vaccines. They will be given subcutaneously. The injections will be 1/10th of a teaspoon.

MEDICAL TESTS BEFORE STARTING TREATMENT:

Before starting low dose chemotherapy plus oral cytoxan, patients will receive a series of standard medical tests:

* Physical exam

* Blood tests to measure blood cells, blood salts, kidney and liver function

* Measurements of their disease (CT or MRI of the primary tumor site and any locations of tumor spread; MIBG or Bone scan; Chest X-ray if they did not have a CT of the chest; and bone marrow studies if the patient has known bone marrow disease)

* Baseline testing of immune function

* Pregnancy testing will be performed on females of child bearing age

MEDICAL TESTS DURING AND AFTER TREATMENT:

Prior to each vaccine dose, the patient will receive:

* Physical exam

* Blood tests to measure blood cells, blood salts, kidney and liver function

* Measurements of the disease (CT or MRI of the primary tumor site and any locations of tumor spread; MIBG or Bone scan; Chest X-ray if they did not have a CT of the chest; and bone marrow studies if they have known bone marrow disease) after the 4th, 6th and 8th vaccine.

* Testing of immune function

* Pregnancy testing will be performed again on females of child bearing age prior to the 5th vaccine

To learn more about the way the vaccine is stimulating the immune cells, we will collect blood prior to each vaccination and at scheduled time points until 3 months after the last vaccine treatment. The total amount of blood to be collected on any day is no more than 2 ounces, but will depend upon the weight. This volume is considered safe in teens and adults, but may be decreased if the patient is anemic. On days when the patient receives the vaccine, blood will be taken before the cells are given.

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 11

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
Number of Participants with Adverse Events as a Measure of Safety and Tolerability	week 30	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.

Secondary Outcome Measures

Name	Time	Method
Participants with T-cell changes as a Measure of Immune Response	15 years	Phase I Secondary Objective: Evaluate the immune response to combination metronomic chemotherapy and allogeneic tumor cell immunizations.
Number of Participants with Disease Progression as a Measure of Efficacy	10 weeks	Phase II Primary Objective: Evaluate time to progression after administration of combination metronomic chemotherapy and allogeneic tumor cell immunizations in patients with a history of relapsed/refractory high-risk neuroblastoma.