Feasibility of Generating Pluripotent Stem Cells From Patients With Familial Retinoblastoma

Retinoblastoma Clinical Trial

Official title:

Feasibility, Validation and Differentiation of Induced Pluripotent Stem Cells Produced From Patients With Heritable Retinoblastoma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02193724
• Other study ID #: RETCELL
• Status: Completed
• Start date: November 4, 2014
• Est. completion date: August 23, 2019

Study information

• Verified date: October 2020
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The goal of this study is to determine if human RB1-deficient induced pluripotent stem cells (iPSCs) can produce retina, and, furthermore, can give rise to retinoblastoma in culture. This unique opportunity to study the initiation of retinoblastoma in the developing retina will shed light on the cell of origin for retinoblastoma and allow the investigators to study the earliest molecular and cellular events in retinoblastoma tumorigenesis. OBJECTIVES: - To establish the feasibility of producing induced pluripotent stem cells (iPSCs) from retinoblastoma patients with germline RB1 mutations (RB1-deficient iPSCs). - To validate human RB1-deficient iPSCs by confirming karyotype, pluripotency and RB1 mutation. - To differentiate the RB1-deficient iPSCs into retina as a model of the initiation of retinoblastoma in the developing retina.

Description:

This is an observational study where a small skin cell sample or peripheral blood sample will be used to produce iPSCs. After RB1-deficient iPSCs are produced, their karyotype and RB1 mutation will be confirmed and their pluripotency will be tested by studying the expression of pluripotent genes and proteins according to standardized guidelines established for human iPSCs. After validation of the RB1-deficient iPSCs, they will be differentiated in the laboratory into retina following established protocols.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: August 23, 2019
• Est. primary completion date: August 23, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Research participant with heritable retinoblastoma and one of the following criteria:
• Family history with RB1 mutation identified
• Diagnosis of bilateral retinoblastoma
• Diagnosis of unilateral retinoblastoma with RB1 mutation or MYCN amplification identified
• Participant or legal guardian/representative is able and willing to provide written informed consent.

Exclusion Criteria:

• Participants who do not meet the inclusion criteria will be excluded.

Related Conditions & MeSH terms

• Retinoblastoma

Intervention

Other:
• Skin Biopsy
A very small skin sample will be taken from the participant's arm. This will only be performed while the patient is under sedation for clinical purposes (e.g. exam under anesthesia, MRI, or other procedure requiring sedation).
• Blood Draw
About 1 teaspoon of blood will be drawn from the participant's arm or from a central line catheter if present. Blood collection will be done at the same time the participant has blood drawn for routine clinical care.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (2)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	University of Wisconsin, Madison

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of samples which successfully produced iPSCs	Skin biopsy or peripheral blood mononuclear cells will be collected from eligible, consenting participants and shipped directly to the University of Wisconsin for processing. All samples will be returned to the St. Jude investigator within two months of reprogramming for further analysis.	Once at enrollment
Secondary	Number of samples with validated RB1-deficient iPSCs	Samples will be analyzed for standard G band karyotype and FISH analysis (RB1 probe), targeted RB1 mutation (based on known mutation of patient from whom the sample was derived), and validation of pluripotency based on standard protocols.	Once at enrollment
Secondary	Number of samples that differentiate human iPSCs toward an eye field fate	The best available methodology will be utilized for analyses of the RB1-deficient iPSCs.	Once at enrollment

External Links

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