Genetically Modified Cells (KIND T Cells) for the Treatment of HLA-A*0201-Positive Patients With H3.3K27M-Mutated Glioma

NCT05478837 | Active Not Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 210813NCI-2022-05420PICI0029
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I, first-in-human trial tests the safety, side effects, and best dose of genetically modified cells called KIND T cells after lymphodepletion (a short dose of chemotherapy) in treating patients who are HLA-A\*0201-positive and have H3.3K27M-mutated diffuse midline glioma. KIND T cells are a type of treatment in which a patient's T cells (a type of immune system cell) are changed in the laboratory into KIND T cells so they will recognize certain markers found in tumor cells. Drugs such as cyclophosphamide and fludarabine are chemotherapy drugs used to decrease the number of T cells in the body to make room for KIND T cells. Giving KIND T cells after cyclophosphamide and fludarabine may be more useful against cancer compared to the usual treatment for patients with H3.3K27M-mutated diffuse midline glioma (DMG).

Conditions

Diffuse Midline Glioma, H3 K27M-Mutant

Keywords

Autologous T Cells; KIND T Cells; HLA-A*0201-Positive

Outcome Measures

Primary Outcomes (2)

• Frequency and severity of adverse events

  To determine the safety and tolerability of a single intravenous (IV) infusion of KIND T cells in HLA A\*0201+ participants with H3.3K27M+ diffuse midline gliomas

  Up to 28 days following infusion of autologous anti-H3.3K27M TCR-expressing T-cells (KIND T cells)

• Percent of successfully manufactured KIND T cells

  To determine feasibility of a single intravenous (IV) infusion of KIND T cells in HLA A\*0201+ participants with H3.3K27M+ diffuse midline gliomas

  Up to 24 months

Secondary Outcomes (2)

• Percentage of participants who receive KIND T cells

  Up to 12 months

• Duration of KIND T cells in-vivo persistence

  Up to 12 months

Study Arms (1)

Treatment (KIND T cells, cyclophosphamide, fludarabine)

EXPERIMENTAL

Patients receive fludarabine IV on days -4, -3, and -2 and cyclophosphamide IV on day -2 in the absence of disease progression or unacceptable toxicity for the conditioning regimen. Patients also receive KIND T cells IV at dose level 1 (2 x 106 dextramer®+ CD8+ cells/kg) on day 0. If no DLTs are reported, newly enrolling participants may receive dose level 2 of KIND T cells on day 0.

Drug: Cyclophosphamide; Drug: Fludarabine; Biological: Autologous Anti-H3.3K27M TCR-expressing T-cells

Interventions

Fludarabine DRUG

Given IV

Also known as: Fludara

Treatment (KIND T cells, cyclophosphamide, fludarabine)

Cyclophosphamide DRUG

Given IV

Also known as: Cytoxan, Cycloblastin

Treatment (KIND T cells, cyclophosphamide, fludarabine)

Autologous Anti-H3.3K27M TCR-expressing T-cells BIOLOGICAL

Given IV

Also known as: KIND T cells

Treatment (KIND T cells, cyclophosphamide, fludarabine)

Eligibility Criteria

• Age: 2 Years - 25 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Participants 2 to 25 years of age inclusive, at the time of signing the informed consent. The first two participants will be 12-25 years of age.
• Male participants of impregnate potential must agree to use contraception, during the study and for at least 6 months after the last study intervention and refrain from donating sperm during this period.
• Female participants of childbearing potential must agree to follow the contraceptive guidance, during the study and for at least 6 months after the last study intervention.
• Females of childbearing potential must have a negative serum or urine pregnancy test within 14 days of receiving study interventions.
• CNS reservoir such as Ommaya catheter must be in place.
• Patients must be enrolled on PNOC COMP prior to enrollment on PNOC018 if PNOC COMP is open to accrual at the enrolling institution.
• Participants with DMG who are positive for the H3.3K27M mutation (positive testing from a Clinical Laboratory Improvement Amendments (CLIA) laboratory required or equivalent) and who completed at least standard radiation therapy.
• All participants must test positive for HLA-A\*0201 (positive testing from a CLIA or equivalent laboratory required). Other HLA-A2 subtypes are excluded.
• All participants must consent for tumor tissue (fresh or archival) for biomarker analysis if available.
• All participants must have evaluable or measurable disease at the time of consent.
• All participants must be either off systemic steroids or be on a stable or declining dose of dexamethasone (maximum dose of 0.1 mg/kg/day or 4 mg/day) at the time of enrollment.
• Participants must not have received any bone marrow transplants for the treatment of their tumor.
• Participants must discontinue all anti-cancer agents and radiotherapy and, must have recovered from significant acute toxic effects of prior therapies.
• Chemotherapy/biologic therapy: All cytotoxic chemotherapy/biologic therapy must be discontinued ≥ 7 days prior to enrollment.
• Immunotherapy: The last dose of anti-tumor antibody therapy must be at least 3 half-lives or 30 days, whichever is shorter, from the time of enrollment.

You may not qualify if:

• Participants are excluded from the study if any of the following criteria apply:
• Participants with MRI or clinical evidence of uncontrolled tumor mass effect; the assessment of mass effect should be made by the study investigators prior to any planned KIND T cell treatment. Pre-infusions MRI will need to be reviewed by the study investigators prior to dosing. Participants with an assessment score \>= 3 will be excluded, based on Table 4 in section 3.8.2
• Participants with a known disorder that affects their immune system such as HIV or hepatitis B or C, or an autoimmune disorder requiring systemic cytotoxic or immunosuppressive therapy. Participants who are currently using inhaled, intranasal, ocular, topical, or other non-oral or non-IV steroids are not necessarily excluded from the study.
• Participants who have received prior solid organ or bone marrow transplantation.
• Participants with uncontrolled infection.
• Female participants of childbearing potential must not be pregnant or breast-feeding.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Untreated symptomatic hydrocephalus determined by treating physician.
• Participants who are unable to return for follow-up visits or obtain follow-up studies required to assess toxicity to therapy.
• Participants who are currently receiving another investigational drug.
• Participants who are co-enrolled on another investigational protocol.

Sponsors & Collaborators

• University of California, San Francisco: lead
• The V Foundation: collaborator
• Parker Institute for Cancer Immunotherapy: collaborator
• Alliance for Cancer Gene Therapy: collaborator

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

Location

MeSH Terms

Interventions

Cyclophosphamide; fludarabine; fludarabine phosphate

Intervention Hierarchy (Ancestors)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds

Study Officials

• Sabine Mueller, MD, PhD, MAS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Hideho Okada, MD, PhD

  University of California, San Francisco

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: July 26, 2022
• First Posted: July 28, 2022
• Study Start: July 20, 2023
• Primary Completion (Estimated): August 31, 2029
• Study Completion (Estimated): August 31, 2029
• Last Updated: March 31, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL

Locations

US (1)