Allogeneic Neuroblastoma Cells for Relapsed/ Refractory Neuroblastoma, CYCHEALL
CYCHEALL
Phase 1 Study of Chemokine and Cytokine Gene Modified Allogeneic Neuroblastoma Cells for Treatment of Relapsed/Refractory Neuroblastoma Using a Retroviral Vector (CYCHEALL)
2 other identifiers
interventional
32
1 country
2
Brief 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. 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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Dec 1997
Longer than P75 for phase_1
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
December 1, 1997
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2001
CompletedFirst Submitted
Initial submission to the registry
October 22, 2012
CompletedFirst Posted
Study publicly available on registry
October 24, 2012
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2016
CompletedJuly 12, 2023
July 1, 2023
3.1 years
October 22, 2012
July 10, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
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.
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.
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.
3 weeks
Assess the antitumor effect by routine clinical response evaluation by imaging.
8 weeks
Study Arms (1)
Injection of allogeneic neuroblastoma cells
EXPERIMENTALRetrovirally 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.
Interventions
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.
Eligibility Criteria
You may qualify if:
- 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.
- Patients must have ECOG performance status of 0-2 as below:
- Grade Activity
- Up and about, no restriction.
- Ambulatory, no strenuous activity.
- 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.
- Limited self-care only. Up and about \<50% of time.
- 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.
You may not qualify if:
- Patients must not be HIV-positive.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (2)
Houston Methodist Hospital
Houston, Texas, 77030, United States
Texas Children's Hospital
Houston, Texas, 77030, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Malcom Brenner, MD, PhD
Baylor College of Medicine
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
- Director/Professor Center for Gene Therapy
Study Record Dates
First Submitted
October 22, 2012
First Posted
October 24, 2012
Study Start
December 1, 1997
Primary Completion
January 1, 2001
Study Completion
April 1, 2016
Last Updated
July 12, 2023
Record last verified: 2023-07