Allogeneic Tumor Cell Vaccination With Oral Metronomic Cytoxan in Patients With High-Risk Neuroblastoma
| Status: | Active, not recruiting |
|---|---|
| Conditions: | Cancer, Brain Cancer |
| Therapuetic Areas: | Oncology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 3/14/2019 |
| Start Date: | September 2010 |
| End Date: | September 2026 |
A Phase I/II Study Using Allogeneic Tumor Cell Vaccination With Oral Metronomic Cytoxan in Patients With High-Risk Neuroblastoma (ATOMIC)
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.
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.
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.
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.
INCLUSION CRITERIA:
- 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.
EXCLUSION CRITERIA:
- 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
We found this trial at
1
site
Texas Children's Hospital Texas Children's Hospital, located in Houston, Texas, is a not-for-profit organization whose...
Click here to add this to my saved trials
