LeukemiaNCT02564484
iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy
An observational study of Leukemia and Lymphoma, run by St. Jude Children's Research Hospital at 1 site in United States.
Trial summary
This observational study is designed to establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons for comparing their sensitivity to vincristine and other potentially neurotoxic drugs. Read more about this study
- Who is it for?
- Ages 18 years and older
- How many people
- 137 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Feb 2016to 9 Jul 2024
- Phase
- Observational
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Cases and controls for this study will be recruited from among the acute lymphocytic leukemia (ALL) survivor members of the St. Jude Lifetime Cohort study (SJLIFE). Cases will be matched for gender, tumor type, estimated cumulative vincristine dose at which toxicity occurred, intended vincristine chemotherapy regimen, age (within 5 years) and race with existing controls.
Who may be able to join
- Adult survivor of childhood ALL
- Presence of any neuromotor, neurocortical, or neurocerebellar toxicity after vincristine treatment (either acute and/or persistent neuropathy)
- At least 50% of the persistent vincristine neuropathy cases will have the CEP72 promoter variant (rs924607) or a coding variant in CEP72 that is predicted to be damaging (CADD score >9). The balance of neuropathy cases will either have variants in other genes that are associated with vincristine neuropathy identified in the ongoing genome-wide association study (GWAS) of 1250 St. Jude Life ALL survivors, or have neuropathy in the absence of known genetic variants altering the risk of neuropathy.
- Patient understands the nature of the study and provides informed consent
- Adult survivor of childhood diagnosis of ALL
- Absence of persistent neurotoxicity (grade 0) after completion of a standard vincristine-containing chemotherapy regimen (may or may not have experience acute neuropathy during treatment.
Show all 10Show fewer
- Matched to a specified subject with neurotoxicity based on age (within 5 years), tumor type, chemotherapy regimen or total vincristine dosage, race and ethnicity.
- At least 50% of the controls will have the CEP72 promoter variant T/T genotype (at rs924607) or a coding variant in CEP72 that is predicted to be damaging (CADD score >9). The balance of controls will either have variants in other genes that are associated with vincristine neuropathy identified in the ongoing GWAS of 1250 St. Jude Life ALL survivors, or will not have a known genetic variant altering the risk of neuropathy.
- Patient understands the nature of the study and provides informed consent
- Individuals of both genders, all races and ethnic groups are eligible for this protocol.
Who cannot join
- Treatment with other severely neurotoxic chemotherapy (i.e. cisplatin) prior to or concomitantly with vincristine. Carboplatin therapy is allowed
- Presence of peripheral neuropathy prior to vincristine therapy
- Poorly controlled or insulin-dependent diabetes or other condition likely to predispose to neurotoxicity
- Pregnant females
- Currently receiving treatment for cancer
Trial locations and contacts
1 site in 1 country.
United States1 site
St. Jude Children's Research Hospital
Memphis, Tennessee, 38105
About this study
Official title: Collection of PBMC's From Patients With Unusually Severe Vincristine-Induced Neuropathy for the Creation of Neuronal-Like Cells
This observational study is designed to establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons for comparing their sensitivity to vincristine and other potentially neurotoxic drugs.
Investigators will assess the effects of inherited genome variations on treatment-induced peripheral neuropathy that persists in adults who were cured of childhood cancer. Cells from childhood cancer survivors who did or did not develop drug-induced neuropathy will be isolated and induced to become neurons. Cell sensitivity to anticancer agents will be tested in both groups and compared to determine if the survivors have genetic variants that correspond to those identified in companion genomic studies. This will assist in determining if gene variants increase the risk of treatment-induced neurotoxicity.
The investigators are interested in detecting changes of phenotype pre-post treatment in each group (cases, controls) respectively, as well in comparing the pre-post treatment phenotypic changes between the two groups (cases vs. controls).
Read the detailed description
Participants will be recruited from an existing protocol at St. Jude (SJLIFE, NCT00760656). Complete neuropathic evaluations are obtained as part of SJLIFE, and the information will be shared for use in the SJLPSC study. A one-time blood draw will be obtained, and peripheral blood mononuclear cells (PBMC's) will be isolated for eventual creation of induced pluripotent stem cells (iPSC) that will be differentiated into human neurons. These human neurons will allow the investigators to functionally validate and further interrogate CEP72 genetic variants or variants in other genes that are associated with persistent (or acute) vincristine neuropathy using a "state of the art" cellular model of human neurons. Furthermore, creating neurons from patients at the extremes (highly sensitive to vincristine-induced neuropathy and matched controls) allows the study of differences at baseline and after treatment with vincristine.
PRIMARY OBJECTIVE:
- To establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons to assess their sensitivity to vincristine and determine whether neurons from patients who developed neuropathy are more sensitive to vincristine or other neurotoxic chemotherapy.
SECONDARY OBJECTIVE:
- To evaluate the iPSC neurons made from patients with persistent treatment-related neuropathy and iPSC neurons from patients who did not develop neuropathy from the same treatment, for phenotypic difference prior to and after exposure to vincristine or other potentially neurotoxic medications.
- Keywords
- Cancer Therapy, Pharmacogenomics, Drug Response, Genetic Variants, Vincristine-Induced Neuropathy, Cancer Survivor
- Medical subject headings
- Leukemia, Lymphoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Neuropathy | Adult survivors who developed persistent treatment-related neuropathy. | |
| Control | Adult survivors who did not develop persistent treatment-related neuropathy. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants for whom iPSCs were created
Blood will be drawn on Day 1, processed and sent to the University of Chicago for infectious diseases testing and creation of PBMCs for eventual development of iPS cells.
Measured: Up to 6 months after participant enrollment
Secondary outcomes (1)
Phenotype differences
Cell phenotypes of the iPSC neurons made from each patient (case or control) will be observed before and after treatment of neurotoxic drugs, giving for each drug a pair of observations from a patient.
Measured: Up to 6 months after participant enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2015 (estimated)
- Study start8 Feb 2016
- Primary completion12 May 2021
- Study completion9 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for LeukemiaStudies of the same condition, open and under way.
- More trials run by St. Jude Children's Research HospitalThe 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
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 137 participants (actual)
Sponsor and investigators
- Lead sponsor
- St. Jude Children's Research Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- University of Chicago, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- William E. Evans, PharmD, Principal investigator, St. Jude Children Research Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02564484
- Sponsor's protocol ID
- SJLPSC
- Other IDs
- R01CA036401
- Status last verified
- Aug 2024
- First submitted
- 29 Sep 2015
- Last updated
- 15 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Collection of PBMC's From Patients With Unusually Severe Vincristine-Induced Neuropathy for the Creation of Neuronal-Like Cells
- ClinicalTrials.gov ID
- NCT02564484
- Acronym / sponsor ID
- SJLPSC
- Keywords
- Cancer Therapy, Pharmacogenomics, Drug Response, Genetic Variants, Vincristine-Induced Neuropathy, Cancer Survivor
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 137 participants (actual)
- Lead sponsor
- St. Jude Children's Research HospitalUniversity, hospital or other
- Collaborators
- University of Chicago, National Cancer Institute (NCI)
- Study start
- 8 Feb 2016 (actual)
- Primary completion
- 12 May 2021 (actual)
- Study completion
- 9 Jul 2024 (actual)
- First posted
- 30 Sep 2015 (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.
This observational study is designed to establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons for comparing their sensitivity to vincristine and other potentially neurotoxic drugs.
Investigators will assess the effects of inherited genome variations on treatment-induced peripheral neuropathy that persists in adults who were cured of childhood cancer. Cells from childhood cancer survivors who did or did not develop drug-induced neuropathy will be isolated and induced to become neurons. Cell sensitivity to anticancer agents will be tested in both groups and compared to determine if the survivors have genetic variants that correspond to those identified in companion genomic studies. This will assist in determining if gene variants increase the risk of treatment-induced neurotoxicity.
The investigators are interested in detecting changes of phenotype pre-post treatment in each group (cases, controls) respectively, as well in comparing the pre-post treatment phenotypic changes between the two groups (cases vs. controls).
Detailed description
Participants will be recruited from an existing protocol at St. Jude (SJLIFE, NCT00760656). Complete neuropathic evaluations are obtained as part of SJLIFE, and the information will be shared for use in the SJLPSC study. A one-time blood draw will be obtained, and peripheral blood mononuclear cells (PBMC's) will be isolated for eventual creation of induced pluripotent stem cells (iPSC) that will be differentiated into human neurons. These human neurons will allow the investigators to functionally validate and further interrogate CEP72 genetic variants or variants in other genes that are associated with persistent (or acute) vincristine neuropathy using a "state of the art" cellular model of human neurons. Furthermore, creating neurons from patients at the extremes (highly sensitive to vincristine-induced neuropathy and matched controls) allows the study of differences at baseline and after treatment with vincristine.
PRIMARY OBJECTIVE:
- To establish induced pluripotent stem cells (iPSCs) from childhood cancer survivors who did or did not develop persistent treatment-induced peripheral neuropathy, from which to make human neurons to assess their sensitivity to vincristine and determine whether neurons from patients who developed neuropathy are more sensitive to vincristine or other neurotoxic chemotherapy.
SECONDARY OBJECTIVE:
- To evaluate the iPSC neurons made from patients with persistent treatment-related neuropathy and iPSC neurons from patients who did not develop neuropathy from the same treatment, for phenotypic difference prior to and after exposure to vincristine or other potentially neurotoxic medications.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Neuropathy | – | –Adult survivors who developed persistent treatment-related neuropathy. |
| Control | – | –Adult survivors who did not develop persistent treatment-related neuropathy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Cases and controls for this study will be recruited from among the acute lymphocytic leukemia (ALL) survivor members of the St. Jude Lifetime Cohort study (SJLIFE). Cases will be matched for gender, tumor type, estimated cumulative vincristine dose at which toxicity occurred, intended vincristine chemotherapy regimen, age (within 5 years) and race with existing controls.
Key inclusion criteria (10 listed)
- Adult survivor of childhood ALL
- Presence of any neuromotor, neurocortical, or neurocerebellar toxicity after vincristine treatment (either acute and/or persistent neuropathy)
- At least 50% of the persistent vincristine neuropathy cases will have the CEP72 promoter variant (rs924607) or a coding variant in CEP72 that is predicted to be damaging (CADD score >9). The balance of neuropathy cases will either have variants in other genes that are associated with vincristine neuropathy identified in the ongoing genome-wide association study (GWAS) of 1250 St. Jude Life ALL survivors, or have neuropathy in the absence of known genetic variants altering the risk of neuropathy.
- Patient understands the nature of the study and provides informed consent
- Adult survivor of childhood diagnosis of ALL
Key exclusion criteria (5 listed)
- Treatment with other severely neurotoxic chemotherapy (i.e. cisplatin) prior to or concomitantly with vincristine. Carboplatin therapy is allowed
- Presence of peripheral neuropathy prior to vincristine therapy
- Poorly controlled or insulin-dependent diabetes or other condition likely to predispose to neurotoxicity
- Pregnant females
- Currently receiving treatment for cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Number of participants for whom iPSCs were created
Time frame: Up to 6 months after participant enrollment
Blood will be drawn on Day 1, processed and sent to the University of Chicago for infectious diseases testing and creation of PBMCs for eventual development of iPS cells.
1 secondary outcome
Phenotype differences
Time frame: Up to 6 months after participant enrollment
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 15 Aug 2024.
- St. Jude Children's Research HospitalLink provided by the sponsor.
- Clinical Trials Open at St. JudeLink provided by the sponsor.
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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.
William E. Evans, PharmD principal investigator
St. Jude Children Research Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Leukemia and Lymphoma, run by St. Jude Children's Research Hospital at 1 site 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 10 inclusion and 5 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 15 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
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?
Number of participants for whom iPSCs were created (time frame: Up to 6 months after participant enrollment). 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 15 Aug 2024.