NeuroblastomaPhase 1CYCHEALLNCT01713439
Allogeneic Neuroblastoma Cells for Relapsed/ Refractory Neuroblastoma, CYCHEALL
A Phase 1 study testing Injection of allogeneic neuroblastoma cells in people with Neuroblastoma, run by Baylor College of Medicine at 2 sites in United States.
Trial summary
The patient's have neuroblastoma that has come back, or not gone away. The cancer is harder to treat now. The investigators would like the patient's to be in this research study to determine the safety and dosage of special cells that may make the patient's own immune system fight the cancer. Read more about this study
- Who is it for?
- Ages Up to 21 years
- Conditions the study is for
- Neuroblastoma
- What is being tested?
- Injection of allogeneic neuroblastoma cells
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 1997to Apr 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- All patients under 21 years of age at diagnosis with recurrent, advanced stage neuroblastoma shall be eligible for this protocol.
- Patients must have a life expectancy of at least 8 weeks.
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute lymphocyte and neutrophil count of >500/mm3 each.
- Patients must not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six months.
- Patients must have bilirubin <1.5 mg%.
- Patients must have creatinine <1.5 mg/dl.
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- Patients must have ECOG performance status of 0-2 as below:
- Grade Activity
- 0 Up and about, no restriction.
- 1 Ambulatory, no strenuous activity.
- 2 Ambulatory, capable of self-care appropriate for age.Up and about >50% of time, but unable to carry out any physical activities or attend school.
- 3 Limited self-care only. Up and about <50% of time.
- 4 Disabled, no self care. Bedridden or confined to chair.
- Patients must be willing to utilize one of the more effective birth control methods during the study and for six(6) months after the study is concluded. The male partner should use a condom.
- Patients or legal guardians must sign an informed consent indicating that they are aware this is a research study and have been told of its possible benefits and toxic side effects. Patients or their guardians will be given a copy of the consent form.
Who cannot join
- Patients must not be HIV-positive.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Houston Methodist Hospital
Houston, Texas, 77030
Texas Children's Hospital
Houston, Texas, 77030
About this study
Official title: Phase 1 Study of Chemokine and Cytokine Gene Modified Allogeneic Neuroblastoma Cells for Treatment of Relapsed/Refractory Neuroblastoma Using a Retroviral Vector (CYCHEALL)
The patient's have neuroblastoma that has come back, or not gone away. The cancer is harder to treat now. The investigators would like the patient's to be in this research study to determine the safety and dosage of special cells that may make the patient's own immune system fight the cancer. To do this the investigators will put two special genes into neuroblastoma cancer cells that have been grown in the lab. The genes put in make the cancer cells produce lymphotactin, a natural substance that attracts immune system cells to the cancer, and IL-2 a natural substance that may help the immune system kill cancer cells. Some of these cells will then be put into the patient's body. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that substances like lymphotactin and IL-2 do help the body kill cancer cells. A treatment similar to this has been used in twelve children previously and similar treatments are being used in adults with other cancers. This is a research study. The investigators do not know the best amount of special cells to use, so different children will get different numbers of cells.
The purpose of this study is to learn the side effects and safe "dosage" of these special cells. Participation in this study will last for 15 years.
Read the detailed description
The investigators have grown neuroblastoma cells in the laboratory and put into them two specially produced mouse viruses (retroviruses) that carry the lymphotactin and the IL-2 gene. These lymphotactin and IL-2 genes are meant to help the immune system fight the cancer. The modified cancer cells will be injected under the patient's skin. There will be four shots. The second and subsequent shots will have ten times as many cells producing lymphotactin as the first. The patient will normally have these shots as an outpatient. Depending on response (if the patient's cancer has stayed the same or gotten smaller), the patient may be able to have four more of these shots.
Tests during and after treatment:
If the patient's blood has not been tested for HIV, the virus that causes AIDS, then the investigators will need to do this test. If this virus is present, this research treatment cannot be used.
Before the second shot, and then again about 2 weeks later, the investigators will remove some of the modified cells from the patient's body and study them. This will be done by a skin biopsy at the place where the cells were injected. These tests are to see whether the changes made in the laboratory are killing cancer cells.
To study how the immunity is working in the patient's body blood samples will be taken two to four days after each injection. This may be repeated 5-7 days after each injection if the patient's doctor thinks that it is necessary. After the patient stops receiving the injections, the blood draws will need to be repeated once a month for a year, and then once a year for fifteen years.
The patient will need to come to the clinic on the days the investigators take blood and will need to be seen at Texas Children's Cancer Center at weekly intervals for 6 weeks, then every other week for 6 weeks, and then monthly for a year. Then the patient will be seen in clinic or contacted by study personnel once a year for 15 years. Additional visits may be necessary.
To see if this research treatment is working, CAT scans, MRIs, or bone scans (these are different types of x-rays)will be done. Investigators will also take a bone marrow biopsy (bone marrow will be removed by use of a needle so that it can be looked at under the microscope). These tests will be done prior to treatment and repeated eight weeks later. In addition, if the patient receives the second set of four injections, these tests will be repeated at six months. If the neuroblastoma is not responding (if it has gotten larger), the investigators will offer the patient treatment with chemotherapy and/or radiation therapy.
- Conditions
- Neuroblastoma
- Being tested
- Injection of allogeneic neuroblastoma cells
- Keywords
- Relapsed/Refractory Neuroblastoma, Retroviral vector injections, Allogeneic neuroblastoma cells, Lymphotactin, Interleukin-2 (IL-2)
- Medical subject headings
- Neuroblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Injection of allogeneic neuroblastoma cellsBiological
Patients will receive a fixed dose of IL-2 gene modified tumor cells (10^7/kg, 10^8 max) already shown to be safe from a previous protocol, and an escalating dose of Lptn transduced tumor cells, beginning at 10^4/kg and rising to 10^7/kg (10^8 max). Patients will be assigned to an appropriate dose level for injection # 1. Injection #2 will contain 10 times more Lptn transduced cells than injection #1, until the max dose (10^8) has been reached in the first injection. The dose of injections 3 through 8 will be the same as the dose of injection #2. Initial injection volumes will be <1ml and should be injected in a single site. Only if these first patients show no undue local toxicity (including tumor cell growth) will multiple injection sites be used for subsequent high cell-dose studies.
| Study group | Role | What they receive |
|---|---|---|
| Injection of allogeneic neuroblastoma cells | Experimental | Retrovirally transduced allogeneic neuroblastoma cell lines secreting the human interleukin-2 and lymphotactin genes are frozen and, when needed, are thawed, mixed and irradiated. Relapsed or refractory patients are then treated with a course of four injections of their gene-modified tumor cells according to the following schedule: The first two injections will be given at week 1 and week 2. Patients will then have a two-week rest and the remaining two injections will be given at week 4 and week 5. A complete evaluation for evidence of toxicity and response will be performed at week 8 after a 3 week rest. At the 8 week evaluation, in the absence of progressive disease requiring therapy without excessive toxicity and if more transduced cells are available, the patient will have the option to receive four additional SC injections each separated by 1 month at the higher of the two dosage levels they originally received. Receives: Biological: Injection of allogeneic neuroblastoma cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the safety of up to four subcutaneous (SC) injections of allogeneic neuroblastoma cells which have been genetically modified by measuring adverse events.
The patients will be given four injections as per the protocol schedule with the evaluation at Week 8 (month 2). This will constitute a course and the evaluation of the dose limiting toxicity will be done during this course. Any patient having grade 4 toxicity or having progressive disease during the course will be considered a failure.
Measured: 8 weeks
To assess the safety of up to eight (total) injections in patients who have received the first four injections without unacceptable toxicity and have evidence of stable disease or better after receiving these injections by measuring adverse events.
The second course consists of administering another four injections as per the protocol schedule and evaluating at week 24 (6 months). The second course is conditional upon patients completing the first course with acceptable toxicity. This means that there will be at least 5 patients eligible to receive the second course.
Measured: 6 months
Secondary outcomes (2)
To determine whether MHC restricted or unrestricted antitumor immune responses are induced by SC injection of modified allogeneic neuroblasts and the cell doses required to produce these effects measured by punch biopsies.
For all the patients punch biopsies at the injection site will be done. From this a qualitative assessment of number of CD4 or CD8 or both types of cells will be made in order to understand the immune response.
Measured: 3 weeks
Assess the antitumor effect by routine clinical response evaluation by imaging.
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2012 (estimated)
- Study startDec 1997
- Primary completionJan 2001
- Study completionApr 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NeuroblastomaStudies of the same condition, open and under way.
- More trials run by Baylor College of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Baylor College of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine, St. Jude Children's Research Hospital
- Responsible party
- Principal investigator, Malcolm Brenner, Baylor College of Medicine
- Investigators
- Malcom Brenner, MD, PhD, Principal investigator, Baylor College of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01713439
- Sponsor's protocol ID
- H-6441 CYCHEALL
- Other IDs
- CYCHEALL
- Acronym
- CYCHEALL
- Status last verified
- Jul 2023
- First submitted
- 22 Oct 2012
- Last updated
- 12 Jul 2023
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 12 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase 1 Study of Chemokine and Cytokine Gene Modified Allogeneic Neuroblastoma Cells for Treatment of Relapsed/Refractory Neuroblastoma Using a Retroviral Vector (CYCHEALL)
- ClinicalTrials.gov ID
- NCT01713439
- Acronym / sponsor ID
- CYCHEALL / H-6441 CYCHEALL
- Conditions
- Neuroblastoma
- Keywords
- Relapsed/Refractory Neuroblastoma, Retroviral vector injections, Allogeneic neuroblastoma cells, Lymphotactin, Interleukin-2 (IL-2)
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Baylor College of MedicineUniversity, hospital or other
- Collaborators
- The Methodist Hospital Research Institute, Center for Cell and Gene Therapy, Baylor College of Medicine, St. Jude Children's Research Hospital
- Study start
- Dec 1997 (actual)
- Primary completion
- Jan 2001 (actual)
- Study completion
- Apr 2016 (actual)
- First posted
- 24 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The patient's have neuroblastoma that has come back, or not gone away. The cancer is harder to treat now. The investigators would like the patient's to be in this research study to determine the safety and dosage of special cells that may make the patient's own immune system fight the cancer. To do this the investigators will put two special genes into neuroblastoma cancer cells that have been grown in the lab. The genes put in make the cancer cells produce lymphotactin, a natural substance that attracts immune system cells to the cancer, and IL-2 a natural substance that may help the immune system kill cancer cells. Some of these cells will then be put into the patient's body. Studies of cancers in animals and in cancer cells that are grown in laboratories suggest that substances like lymphotactin and IL-2 do help the body kill cancer cells. A treatment similar to this has been used in twelve children previously and similar treatments are being used in adults with other cancers. This is a research study. The investigators do not know the best amount of special cells to use, so different children will get different numbers of cells.
The purpose of this study is to learn the side effects and safe "dosage" of these special cells. Participation in this study will last for 15 years.
Detailed description
The investigators have grown neuroblastoma cells in the laboratory and put into them two specially produced mouse viruses (retroviruses) that carry the lymphotactin and the IL-2 gene. These lymphotactin and IL-2 genes are meant to help the immune system fight the cancer. The modified cancer cells will be injected under the patient's skin. There will be four shots. The second and subsequent shots will have ten times as many cells producing lymphotactin as the first. The patient will normally have these shots as an outpatient. Depending on response (if the patient's cancer has stayed the same or gotten smaller), the patient may be able to have four more of these shots.
Tests during and after treatment:
If the patient's blood has not been tested for HIV, the virus that causes AIDS, then the investigators will need to do this test. If this virus is present, this research treatment cannot be used.
Before the second shot, and then again about 2 weeks later, the investigators will remove some of the modified cells from the patient's body and study them. This will be done by a skin biopsy at the place where the cells were injected. These tests are to see whether the changes made in the laboratory are killing cancer cells.
To study how the immunity is working in the patient's body blood samples will be taken two to four days after each injection. This may be repeated 5-7 days after each injection if the patient's doctor thinks that it is necessary. After the patient stops receiving the injections, the blood draws will need to be repeated once a month for a year, and then once a year for fifteen years.
The patient will need to come to the clinic on the days the investigators take blood and will need to be seen at Texas Children's Cancer Center at weekly intervals for 6 weeks, then every other week for 6 weeks, and then monthly for a year. Then the patient will be seen in clinic or contacted by study personnel once a year for 15 years. Additional visits may be necessary.
To see if this research treatment is working, CAT scans, MRIs, or bone scans (these are different types of x-rays)will be done. Investigators will also take a bone marrow biopsy (bone marrow will be removed by use of a needle so that it can be looked at under the microscope). These tests will be done prior to treatment and repeated eight weeks later. In addition, if the patient receives the second set of four injections, these tests will be repeated at six months. If the neuroblastoma is not responding (if it has gotten larger), the investigators will offer the patient treatment with chemotherapy and/or radiation therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Injection of allogeneic neuroblastoma cells | Experimental | Biological: Injection of allogeneic neuroblastoma cellsRetrovirally transduced allogeneic neuroblastoma cell lines secreting the human interleukin-2 and lymphotactin genes are frozen and, when needed, are thawed, mixed and irradiated. Relapsed or refractory patients are then treated with a course of four injections of their gene-modified tumor cells according to the following schedule: The first two injections will be given at week 1 and week 2. Patients will then have a two-week rest and the remaining two injections will be given at week 4 and week 5. A complete evaluation for evidence of toxicity and response will be performed at week 8 after a 3 week rest. At the 8 week evaluation, in the absence of progressive disease requiring therapy without excessive toxicity and if more transduced cells are available, the patient will have the option to receive four additional SC injections each separated by 1 month at the higher of the two dosage levels they originally received. |
Who may qualify
- Ages
- Up to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (15 listed)
- All patients under 21 years of age at diagnosis with recurrent, advanced stage neuroblastoma shall be eligible for this protocol.
- Patients must have a life expectancy of at least 8 weeks.
- Patients must have recovered from the toxic effects of all prior chemotherapy before entering this study, and have an absolute lymphocyte and neutrophil count of >500/mm3 each.
- Patients must not be currently receiving any investigational agents or have not received any tumor vaccines within the previous six months.
- Patients must have bilirubin <1.5 mg%.
Key exclusion criteria (1 listed)
- Patients must not be HIV-positive.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Injection of allogeneic neuroblastoma cellsPatients will receive a fixed dose of IL-2 gene modified tumor cells (10^7/kg, 10^8 max) already shown to be safe from a previous protocol, and an escalating dose of Lptn transduced tumor cells, beginning at 10^4/kg and rising to 10^7/kg (10^8 max). Patients will be assigned to an appropriate dose level for injection # 1. Injection #2 will contain 10 times more Lptn transduced cells than injection #1, until the max dose (10^8) has been reached in the first injection. The dose of injections 3 through 8 will be the same as the dose of injection #2. Initial injection volumes will be <1ml and should be injected in a single site. Only if these first patients show no undue local toxicity (including tumor cell growth) will multiple injection sites be used for subsequent high cell-dose studies. | Biological | Injection of allogeneic neuroblastoma cells |
Primary outcome
To assess the safety of up to four subcutaneous (SC) injections of allogeneic neuroblastoma cells which have been genetically modified by measuring adverse events.
Time frame: 8 weeks
The patients will be given four injections as per the protocol schedule with the evaluation at Week 8 (month 2). This will constitute a course and the evaluation of the dose limiting toxicity will be done during this course. Any patient having grade 4 toxicity or having progressive disease during the course will be considered a failure.
To assess the safety of up to eight (total) injections in patients who have received the first four injections without unacceptable toxicity and have evidence of stable disease or better after receiving these injections by measuring adverse events.
Time frame: 6 months
The second course consists of administering another four injections as per the protocol schedule and evaluating at week 24 (6 months). The second course is conditional upon patients completing the first course with acceptable toxicity. This means that there will be at least 5 patients eligible to receive the second course.
2 secondary outcomes
To determine whether MHC restricted or unrestricted antitumor immune responses are induced by SC injection of modified allogeneic neuroblasts and the cell doses required to produce these effects measured by punch biopsies.
Time frame: 3 weeks
Assess the antitumor effect by routine clinical response evaluation by imaging.
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jul 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Malcom Brenner, MD, PhD principal investigator
Baylor College of Medicine
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Injection of allogeneic neuroblastoma cells in people with Neuroblastoma, run by Baylor College of Medicine at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To assess the safety of up to four subcutaneous (SC) injections of allogeneic neuroblastoma cells which have been genetically modified by measuring adverse events. (time frame: 8 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2023.