ADAGiO: Adoptive Cellular Therapy for the TreAtment of Recurrent OliGodendrogliOma (OG) Adult Patients

NCT06254326 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: IRB202301855OCR44817
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This study will enroll 6 DLT evaluable subjects (up to 12 patients total) where we will evaluate feasibility and safety of adoptive cellular therapy combined with IDH1/2 inhibitors in patients with recurrent or progressive oligodendroglioma WHO grade 2 and WHO grade 3.

Conditions

Recurrent Oligodendroglioma; Progressive Oligodendroglioma

Keywords

Immunotherapy; Brain Tumor

Outcome Measures

Primary Outcomes (2)

• Prevalence of enrolled subject who receive qualified immunotherapy investigational product.

  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.

  enrollment up to 9 months

• 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.

  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.

  enrollment to completion of DLT window; up to 9 months.

Study Arms (1)

Adoptive Cellular Therapy

EXPERIMENTAL

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.

Biological: TTRNA-DC vaccines with GM-CSF; Biological: Autologous Hematopoietic Stem cells (HSCs); Biological: TTRNA-xALT; Drug: Td vaccine

Interventions

Autologous Hematopoietic Stem cells (HSCs) BIOLOGICAL

Participants will receive a single infusion of autologous CD34+ HSCs

Adoptive Cellular Therapy

TTRNA-xALT BIOLOGICAL

Participants will receive a single infusion of ex vivo expanded tumor-reactive T cells

Adoptive Cellular Therapy

Td vaccine DRUG

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.

Adoptive Cellular Therapy

TTRNA-DC vaccines with GM-CSF BIOLOGICAL

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

Adoptive Cellular Therapy

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Oligo Nation, Inc: collaborator

Study Sites (1)

University of Florida Health Shands Hospital

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Oligodendroglioma; Brain Neoplasms

Interventions

Granulocyte-Macrophage Colony-Stimulating Factor; Diphtheria-Tetanus Vaccine

Condition Hierarchy (Ancestors)

Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors; Bacterial Vaccines; Vaccines; Biological Products; Complex Mixtures; Diphtheria Toxoid; Toxoids; Tetanus Toxoid; Vaccines, Combined

Study Officials

• Duane Mitchell, MD, PhD

  University of Florida

  STUDY CHAIR

• Ashley Ghiaseddin, MD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2024
• First Posted: February 12, 2024
• Study Start: September 19, 2024
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: March 9, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)