iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy
- Conditions
- LeukemiaLymphoma
- Registration Number
- NCT02564484
- Lead Sponsor
- St. Jude Children's Research Hospital
- Brief 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.
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 137
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Number of participants for whom iPSCs were created 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.
- Secondary Outcome Measures
Name Time Method Phenotype differences Up to 6 months after participant enrollment 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.
Trial Locations
- Locations (1)
St. Jude Children's Research Hospital
🇺🇸Memphis, Tennessee, United States