A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma
Primary Purpose
Osteosarcoma
Status
Recruiting
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
SCRI-E2CAR_EGFRtv1
UB_TT170
Sponsored by
About this trial
This is an interventional treatment trial for Osteosarcoma focused on measuring osteosarcoma, bone cancer, pediatric sarcoma, young adult sarcoma
Eligibility Criteria
Inclusion Criteria:
Refractory or recurrent/progressive osteosarcoma that has failed first line therapy for Osteosarcoma per NCCN or upfront Children's Oncology Group clinical trial and is not amenable to surgical resection (must meet one of the following):
- New site of measurable disease by radiographic imaging or histologic confirmation
- New site of evaluable disease by radiographic imaging (including FDG-PET) or histologic confirmation
- Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a maximum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included)
- Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy and/or chemotherapy)
- Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing
- Life expectancy ≥ 8 weeks
- Lansky or Karnofsky score ≥ 50
- Anti-cancer agents, radiotherapy, cytoxic chemotherapy, biologic therapy, anti-tumor antibody therapy, genetically modified cell therapy, and, if no apheresis product available, corticosteroid therapy (excluding physiologic replacement), discontinued within protocol specified wash-out period
- Adequate hematologic, renal, hepatic, cardiac, and respiratory function.
- Negative HIV, hepatitis B and C test within 3 months
- If of child-bearing or fathering potential, willing to use highly effective contraception through 12 months following final stud drug infusion
Exclusion Criteria:
- Active malignancy other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed)
- Ongoing, symptomatic CNS pathology requiring medical intervention
- Receiving external beam radiotherapy
- Presence of active, severe infection
- Primary immunodeficiency syndrome
- Pregnant or breast feeding
- Unwilling to provide consent/assent for study participation, including 15 year follow up
- Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.
Sites / Locations
- Seattle Children's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
UB-TT170 following SCRI-E2CAR_EGFrtv1
Arm Description
Following CAR T cell administration, subjects will receive a first Course of 3 escalating doses of UB-TT170 over 2 weeks followed by fixed weekly dosing for 2 weeks. If eligible, subjects may proceed to Courses 2 - 4 consisting of 7 weekly doses of UB-TT170.
Outcomes
Primary Outcome Measures
Adverse events associated with ex-vivo expanded autologous T cells genetically modified to express an antiFL(FITC-E2) CAR administered with UB-TT170 will be assessed
The type, frequency, severity, and duration of adverse events will be summarized
Secondary Outcome Measures
Ability to manufacture antiFL(FITC-E2) CAR cells
The number of successfully manufactured antiFL(FITC-E2) CAR products will be assessed
Evaluate the pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells
Pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells
Full Information
NCT ID
NCT05312411
First Posted
March 20, 2019
Last Updated
June 27, 2023
Sponsor
Seattle Children's Hospital
Collaborators
Umoja BioPharma, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05312411
Brief Title
A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma
Official Title
A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-Ew) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 20, 2022 (Actual)
Primary Completion Date
April 30, 2025 (Anticipated)
Study Completion Date
April 30, 2040 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seattle Children's Hospital
Collaborators
Umoja BioPharma, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The purpose of this study is to see if a new treatment could help patients who have osteosarcoma that does not go away with treatment (is refractory) or comes back after treatment (is recurrent).This study is testing a combination of study therapies, UB-TT170 and genetically modified chimeric antigen receptor T lymphocyte (CAR T) cells, which work together in a way that is different from chemotherapy.
In this study, researchers will take some of your blood and remove the T cells in a process called "apheresis". Then the T cells are taken to a lab and changed to CAR T cells that recognize the flags from UB-TT170. Once researchers think they have grown enough CAR T cells, called antiFL(FITC-E2) CAR T cells, to fight your cancer, you may get some chemotherapy to make room in your body for the new cells and then have those cells put back in your body.
A few days after the you get your CAR T cell infusion you will start to get infusions of UB-TT170, with the dose slowly increasing for the first few infusions until you have reached a maximum dose that you will get on a regular schedule. The UB-TT170 will attach to your tumor cells and flag them so that they attract the CAR T cells. When the CAR T cells see the labeled tumor cells they can kill the tumor cells.
The active part of the study lasts about 8 months, and if you get the CAR T cell infusion you will be in long-term follow-up for 15 years.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Osteosarcoma
Keywords
osteosarcoma, bone cancer, pediatric sarcoma, young adult sarcoma
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
21 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
UB-TT170 following SCRI-E2CAR_EGFrtv1
Arm Type
Experimental
Arm Description
Following CAR T cell administration, subjects will receive a first Course of 3 escalating doses of UB-TT170 over 2 weeks followed by fixed weekly dosing for 2 weeks. If eligible, subjects may proceed to Courses 2 - 4 consisting of 7 weekly doses of UB-TT170.
Intervention Type
Biological
Intervention Name(s)
SCRI-E2CAR_EGFRtv1
Intervention Description
Autologous CD4+ and CD8+ T cells that have been genetically modified to express antiFL(FITC-E2)
Intervention Type
Drug
Intervention Name(s)
UB_TT170
Intervention Description
Bispecific small molecule adapter formulated with phosphate buffered saline
Primary Outcome Measure Information:
Title
Adverse events associated with ex-vivo expanded autologous T cells genetically modified to express an antiFL(FITC-E2) CAR administered with UB-TT170 will be assessed
Description
The type, frequency, severity, and duration of adverse events will be summarized
Time Frame
30 days
Secondary Outcome Measure Information:
Title
Ability to manufacture antiFL(FITC-E2) CAR cells
Description
The number of successfully manufactured antiFL(FITC-E2) CAR products will be assessed
Time Frame
28 Days
Title
Evaluate the pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells
Description
Pharmacokinetics of UB-TT170 in combination with the anti-FL(FITC-E2) CAR T cells
Time Frame
25 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
15 Years
Maximum Age & Unit of Time
30 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Refractory or recurrent/progressive osteosarcoma that has failed first line therapy for Osteosarcoma per NCCN or upfront Children's Oncology Group clinical trial and is not amenable to surgical resection (must meet one of the following):
New site of measurable disease by radiographic imaging or histologic confirmation
New site of evaluable disease by radiographic imaging (including FDG-PET) or histologic confirmation
Greater than 20% increase in at least one tumor dimension documented by CT/MRI, AND a maximum absolute increase of 5 mm in longest dimension of existing lesion(s) (previously irradiated lesions may be included)
Persistent measurable disease or FDG-PET avid bone metastasis that has failed to achieve complete remission to upfront conventional therapy (surgery, radiotherapy and/or chemotherapy)
Able to tolerate apheresis, including placement of temporary apheresis catheter, if necessary, or already has an apheresis product available for use in manufacturing
Life expectancy ≥ 8 weeks
Lansky or Karnofsky score ≥ 50
Anti-cancer agents, radiotherapy, cytoxic chemotherapy, biologic therapy, anti-tumor antibody therapy, genetically modified cell therapy, and, if no apheresis product available, corticosteroid therapy (excluding physiologic replacement), discontinued within protocol specified wash-out period
Adequate hematologic, renal, hepatic, cardiac, and respiratory function.
Negative HIV, hepatitis B and C test within 3 months
If of child-bearing or fathering potential, willing to use highly effective contraception through 12 months following final stud drug infusion
Exclusion Criteria:
Active malignancy other than primary malignant solid tumor diagnosis (CNS intracranial metastases are allowed)
Ongoing, symptomatic CNS pathology requiring medical intervention
Receiving external beam radiotherapy
Presence of active, severe infection
Primary immunodeficiency syndrome
Pregnant or breast feeding
Unwilling to provide consent/assent for study participation, including 15 year follow up
Presence of any condition that, in the opinion of the investigator, would prohibit the subject from undergoing treatment under this protocol.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Catherine Albert, MD
Phone
206-987-2106
Email
immunotherapy@seattlechildrens.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catherine Albert, MD
Organizational Affiliation
Seattle Children's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Catherine Albert, MD
Phone
206-987-2106
Email
immunotherapy@seattlechildrens.org
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
A Phase I Feasibility And Safety Study of Fluorescein-Specific (FITC-E2) CAR T Cells In Combination With Parenterally Administered Folate-Fluorescein (UB-TT170) For Osteogenic Sarcoma
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