iPSC Neurons From Adult Survivors of Childhood Cancer Who Have Persistent Vincristine-Induced Neuropathy

NCT02564484 | Completed

• 2 other identifiers: SJLPSCR01CA036401
• Study Type: observational
• Target: 137
• Locations: 1 country
• Sites: 1

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).

Conditions

Leukemia; Lymphoma

Keywords

Cancer Therapy; Pharmacogenomics; Drug Response; Genetic Variants; Vincristine-Induced Neuropathy; Cancer Survivor

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 6 months after participant enrollment

Secondary Outcomes (1)

• Phenotype differences

  Up to 6 months after participant enrollment

Study Arms (2)

Neuropathy

Adult survivors who developed persistent treatment-related neuropathy.

Control

Adult survivors who did not develop persistent treatment-related neuropathy.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

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.

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• St. Jude Children's Research Hospital: lead
• University of Chicago: collaborator
• National Cancer Institute (NCI): collaborator

Study Sites (1)

St. Jude Children's Research Hospital

Memphis, Tennessee, 38105, United States

Location

Related Links

• St. Jude Children's Research Hospital
• Clinical Trials Open at St. Jude

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be obtained from each cohort.

MeSH Terms

Conditions

Leukemia; Lymphoma

Condition Hierarchy (Ancestors)

Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• William E. Evans, PharmD

  St. Jude Children Research Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 29, 2015
• First Posted: September 30, 2015
• Study Start: February 8, 2016
• Primary Completion: May 12, 2021
• Study Completion: July 9, 2024
• Last Updated: August 15, 2024

Record last verified: 2024-08

Locations

US (1)