- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT06254326
ADAGiO: Adoptive Cellular Therapy for the TreAtment of Recurrent OliGodendrogliOma (OG) Adult Patients (ADAGiO)
Study Overview
Status
Detailed Description
After screening consent, subjects will undergo standard of care resection or biopsy for confirmatory diagnosis of disease progression and aseptic collection of tumor material for DNA and RNA extraction and sequencing, amplification, and loading of autologous DCs. Following biopsy and confirmatory pathologic diagnosis, eligible patients will be enrolled in treatment.
After surgery, patients will undergo a G-CSF mobilized pheresis to collect PBMCs for DC generation and CD34+ HSCs. Amplified tumor RNA obtained from surgically resected or biopsied specimens will be used to generate total tumor RNA-pulsed DCs (TTRNA-DCs) manufactured while patients initiate salvage chemotherapy regimen after surgery.
Salvage chemotherapy with IDH1/2 inhibitor will initiate 1-2 weeks after G-CSF mobilized leukapheresis for 1-3 cycles after which, treatment cycles will be paused, and the patients will receive 3 priming TTRNA-DCs vaccines every 2 weeks and undergo a non-mobilized leukapheresis to collect vaccine-boosted lymphocytes for ex vivo T cell expansion and generation of additional TTRNA-DC vaccines. Treatment with IDH1/2 inhibitor will resume with monthly TTRNA-DC vaccines for an additional 1-3 cycles until ex vivo expanded T cells are manufactured.
For ACT, patients will undergo non-myeloablative conditioning with cyclophosphamide /fludarabine. The total immunotherapy regimen will consist of up to 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment), a single i.v. infusion of ex vivo expanded tumor-reactive T cells, and a i.v. single infusion of autologous HSCs.
The duration of treatment from enrollment to completion of DLT window is anticipated to be 7 to 9 months.
Study Type
Enrollment (Estimated)
Phase
- Phase 1
Contacts and Locations
Study Contact
- Name: Phuong Deleyrolle, RN
- Phone Number: 352-273-9000
- Email: phuong.deleyrolle@neurosurgery.ufl.edu
Study Locations
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Florida
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Gainesville, Florida, United States, 32610
- University of Florida Health Shands Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
- Adult
- Older Adult
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Male or female, aged 18 years and above
- Tumor tissue obtained on a screening consent is available.
- Confirmed with recurrent/progressive IDH-mutant 1p/19q co-deleted Oligodendroglioma WHO grade 2 or WHO grade 3, more than 12 weeks from completion of radiation.
- Karnofsky Performance Status ≥ 60
- Must be a candidate for surgery/biopsy
Adequate bone marrow and organ function as defined below:
- ANC ≥ 1,000/mcL
- Platelets ≥ 100,000/mcL
- Hemoglobin ≥ 9 g/dL (can be transfused)
- Serum creatinine ≤ 1.5 x IULN OR Creatinine clearance by Cockcroft-Gault ≥ 60 mL/min for patients with serum creatinine > 1.5 x IULN
- Serum total bilirubin ≤ 1.5 x IULN OR Direct bilirubin ≤ IULN for patients with total bilirubin > 1.5 x IULN
- AST (SGOT) and ALT (SGPT) ≤ 3 x IULN
- For females of childbearing potential, negative serum pregnancy test at enrollment
- For women and men of childbearing potential (WOCBP) must be willing to use acceptable contraceptive methods
Exclusion Criteria:
- Disease progression during treatment with an anti-IDH-1 or anti IDH-2
- Prior invasive malignancy (except for non-melanomatous skin cancer) unless disease free for ≥ 3 years.
- Metastases detected below the tentorium or beyond the cranial vault and leptomeningeal involvement.
- Multifocal disease.
- Corticosteroids equivalent to ≥ 4mg dexamethasone daily.
- HIV, Hepatitis B, or Hepatitis C seropositive.
- Known active infection or immunosuppressive disease.
- Autoimmune disease requiring medical management with immunosuppressant.
- Pregnancy or lactation, due to possible adverse effects on the developing fetus or infant.
- Treatment with another investigational drug or other intervention within 30 days prior to projected first dose of study treatment (Priming phase with TTRNA-DC).
Severe, active co-morbidity, defined as follows:
- Unstable angina and/or congestive heart failure requiring hospitalization.
- Transmural myocardial infarction within the last 6 months.
- Acute bacterial or fungal infection requiring intravenous antibiotics at time of enrollment.
- Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy.
- Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects.
- Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition. The need to exclude patients with AIDS from this protocol is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
- Major medical illnesses or psychiatric impairments that, in the investigator's opinion, will prevent administration or completion of protocol therapy.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Adoptive Cellular Therapy
All participants will receive 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment), a single i.v.
infusion of ex vivo expanded tumor-reactive T cells, and a i.v.
single infusion of autologous HSCs.
|
Participants will receive up to 9 intradermal DC vaccines (three -bi-weekly (q2 weeks) for priming, monthly for additional 2-3 cycles during T cell expansion, and three bi-weekly during T cell engraftment
Participants will receive a single infusion of autologous CD34+ HSCs
Participants will receive a single infusion of ex vivo expanded tumor-reactive T cells
All patients will receive a full Td booster IM vaccine 4-24 hours prior to Vaccine #1 and vaccine site pretreatment with a one-fifth dose of Td intradermally, at the site of planned vaccine, 4-24 hours prior to vaccines #3, #5, #7 and #9.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Prevalence of enrolled subject who receive qualified immunotherapy investigational product.
Time Frame: enrollment up to 9 months
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Feasibility will be measured by the number of patients who receive autologous dendritic cells, T cells and hematopoietic stem cells that meet the FDA IND defined quality assurance and quality control release criteria.
A minimum of 66.7% of enrolled subject must achieve this criterion for feasibility endpoint.
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enrollment up to 9 months
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Incidence of investigational treatment related severe toxicity (Dose-limiting toxicity event) assessed during the period beginning with administration of ex vivo expanded TTRNA T cells through 6 weeks post infusion.
Time Frame: enrollment to completion of DLT window; up to 9 months.
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Safety will be defined as < 1 DLT out of six enrolled and treated subjects during the defined period of administration of ex vivo expanded TTRNA T cells through 6 weeks post infusion.
Investigational treatment related CTCAE V5.0 adverse events 1) Grade III or greater non-neurologic toxicity; 2) Grade III neurologic toxicity that does not improve to Grade II or better within 5 days; or 3) Grade IV neurologic toxicity will be recorded toward DLT.
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enrollment to completion of DLT window; up to 9 months.
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Study Chair: Duane Mitchell, MD, PhD, University of Florida
- Principal Investigator: Ashley Ghiaseddin, MD, University of Florida
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms, Glandular and Epithelial
- Disease Attributes
- Glioma
- Neoplasms, Neuroepithelial
- Neuroectodermal Tumors
- Neoplasms, Germ Cell and Embryonal
- Neoplasms, Nerve Tissue
- Recurrence
- Oligodendroglioma
- Physiological Effects of Drugs
- Immunologic Factors
- Vaccines
Other Study ID Numbers
- IRB202301855
- OCR44817 (Other Identifier: University of Florida)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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