Phase I CB-NK-TGF-ßR2-/NR3C1- in rGBM

NCT04991870 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: 2020-0960NCI-2021-00598
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I trial is to find out the best dose, possible benefits and/or side effects of engineered natural killer (NK) cells containing deleted TGF-betaR2 and NR3C1 (cord blood \[CB\]-NK-TGF-betaR2-/NR3C1-) in treating patients with glioblastoma that has come back (recurrent). CB-NK-TGF-betaR2-/NR3C1- cells are genetically changed immune cells that may help to control the disease.

Conditions

Recurrent Gliosarcoma; Recurrent Supratentorial Glioblastoma; Supratentorial Gliosarcoma

Outcome Measures

Primary Outcomes (1)

• Incidence of dose-limiting toxicities (DLTs) (Group 1)

  Will determine maximum tolerated dose and safety of escalating doses of cord blood (CB)-(NK) cells patients with recurrent glioblastoma. A DLT is defined as any grade \>= 3 adverse event assessed as related to CB-NK cells by the investigator (that is, grade \>= 3 adverse drug reaction; grading according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03.

  Up to 28 days

Secondary Outcomes (5)

• Overall survival (OS)

  From definitive histological diagnosis until the time of death, assessed up to 90 days post-treatment

• Objective response rate (ORR)

  Up to 90 days post-treatment

• Duration of response (DOR)

  From the time of initial response until documented tumor progression per RANO criteria, assessed up to 90 days

• Time to progression (TTP)

  From the date of start of treatment until the tumor progression as defined by RANO, assessed up to 90 days post-treatment

• Progression-free survival (PFS)

  From the start of treatment until the time of first disease progression or relapse (as defined by RANO criteria), or death due to disease, assessed up to 6 months post-treatment

Study Arms (2)

Group 1 (CB-NK-TGF-betaR2-/NR3C1- )

EXPERIMENTAL

Participants will receive CB-NK-TGF-betaR2-/NR3C1- intratumorally over 10 minutes followed by 1 ml of Normal Saline injected over additional 10 min via Ommaya catheter every four weeks for up to 8 doses in the absence of disease progression or unacceptable toxicity.

Biological: Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Group 2 (CB-NK-TGF-betaR2-/NR3C1-, resection)

EXPERIMENTAL

Ommaya catheter will be inserted prior to the 1st injection of NK cells (at the time of screening biopsy). Two weeks prior to Surgical resection participants will receive the 1st dose of CB-NK-TGF-betaR2-/NR3C1- intratumorally over 10 minutes followed by 1 ml of Normal Saline injected over an additional 10 min via Ommaya catheter. Ommaya catheter will be taken out at the time of standard of care surgical resection of the tumor on day 15 and then another one will be inserted at the end of surgery for future IT injections. Beginning 2 weeks after surgery, participants will receive CB-NK-TGF-betaR2-/ NR3C1- intratumorally over 10 minutes followed by 1 ml of Normal Saline injected over additional 10 min via Ommaya catheter every 4 weeks for up to 7 doses (total of 8 doses) in the absence of disease progression or unacceptable toxicity.

Biological: Cord Blood-derived Expanded Allogeneic Natural Killer Cells; Procedure: Resection

Interventions

Resection PROCEDURE

Undergo surgical resection

Also known as: Surgical Resection

Group 2 (CB-NK-TGF-betaR2-/NR3C1-, resection)

Cord Blood-derived Expanded Allogeneic Natural Killer Cells BIOLOGICAL

Given CB-NK-TGF-betaR2-/NR3C1- intratumorally

Also known as: Allogeneic CB-derived Ex vivo-expanded NK Cells, CB-derived Expanded Allogeneic NK Cells, UCB-derived Expanded Allogeneic NK Cells, Umbilical Cord Blood-derived Expanded Allogeneic Natural Killer Cells

Group 1 (CB-NK-TGF-betaR2-/NR3C1- ); Group 2 (CB-NK-TGF-betaR2-/NR3C1-, resection)

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent.
• Male or female participants aged ≥ 12 years on the day of signing informed consent.
• Has histologically confirmed supratentorial World Health Organization grade 4 recurrent astrocytoma to include recurrent IDH WT glioblastoma or gliosarcoma and recurrent IDHmutant grade 4 astrocytoma, and recurrent gliosarcoma with any prior number of recurrences, and who have received prior radiation and temozolomide therapy. Participants will be eligible if the original histology was lower-grade glioma grade 2 or 3 and a subsequent histological diagnosis of recurrent glioblastoma or IDH-mutant grade 4 astrocytoma is made.
• Karnofsky Performance Score (KPS) of \>70 at trial entry. Lansky \>70 at trial entry for patients less than 16.
• Must be at least 12 weeks from receiving conformal radiation, unless RANO criteria for early progression are met.
• A baseline brain MRI with Advance Brain Tumor Imaging (ABTI) must be obtained no more than 30 days prior to study registration
• Patients having undergone recent surgery are eligible so long as they are at least 3 weeks from resection or at least 1 week from stereotactic biopsy and recovered from any operative or perioperative complications.
• Adequate hematological function defined by white blood cell (WBC) count ≥ 3 x 10°9/L with absolute neutrophil count (ANC) ≥ 1.5 x 10°9/L, lymphocyte count ≥ 0.5 x 10°9/L, platelet count ≥ 100 x 10°/L, and Hgb ≥ 9 g/ dL (in absence of blood transfusion).
• Adequate hepatic function defined by a total bilirubin level ≤ 1.5 x ULN, an AST level ≤ 2.5 x ULN, and an ALT level ≤ 2.5 x ULN, and INR ≤ 1.5 10. Adequate renal function defined creatinine ≥ 1.5 X upper limit of normal (ULN) OR creatinine clearance ≥ 60 mL/min for participant with creatinine levels \> 1.5 X institutional ULN
• \. Female participant of childbearing potential should have a negative serum pregnancy test within 14 days (+/-2 working days) of study registration.
• \. Female participants of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study and for 3 months after the last dose of study therapy. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for \> 1 year.
• \. Male participants should agree to use 2 methods of highly effective contraception starting with the first dose of study therapy and for 3 months after the last dose of study therapy.
• \. For the surgical expansion group (Group 2): there must be at least 1 cm2 of contrast-enhancing disease that is considered resectable by the neurosurgeon.

You may not qualify if:

• Has received prior therapy with Gliadel or bevacizumab.
• Has received prior interstitial brachytherapy, implanted chemotherapy, or therapeutics delivered by local injection or convection enhanced delivery.
• Is currently participating in or has participated in a study of cancer directed investigational agent or using an investigational device within 4 weeks since last dose of agent administration or device use, or is planning to continue or start treatment with Optune® during participation in this trial.
• Has known severe hypersensitivity to monoclonal antibodies, any history of anaphylaxis, or recent, within 5 months, history of uncontrolled asthma.
• Has a known history of Human Immunodeficiency Virus (HIV) (positive HIV 1/2 antibodies); HTLV1 and/or HTLV2; active Hepatitis B (e.g., HbsAg reactive) or Hepatitis C (e.g., HCV RNA \[qualitative\] is detected). Patients with prior HBV vaccination (anti-HBs positive, HbsAg negative, anti-HBc negative) will NOT be excluded.
• Has a diagnosis of immunodeficiency or is receiving any immunosuppressive therapy within 7 days prior to study registration.
• Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study Day 0.
• Note: Participants with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Note: If participant received major surgery (other than craniotomy), they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Has had prior radiation therapy less than 12 weeks prior to study registration, unless RANO criteria for early progression are met.
• Has had prior therapy with any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints) such as anti-PD-1, anti-PD-L1, or anti-CTLA-4 antibody within the last three months prior to study registration -.
• Has a known additional malignancy that is progressing or requires active treatment.
• Exceptions include but are not limited to basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy. Any exceptions must be discussed with the protocol PI.
• Has known gliomatous cerebri, extracranial disease, or tumor localized primarily to the brainstem or spinal cord.
• Brain midline shift greater than 0.5 cm or pending herniation seen on baseline MRI ABTI.

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Gliosarcoma

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

Study Officials

• Shiao-Pei S Weathers, MD

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shiao-Pei Weathers, MD

CONTACT

713-792-2883; sweathers@mdanderson.org

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: August 5, 2021
• Study Start: April 28, 2023
• Primary Completion (Estimated): January 31, 2027
• Study Completion (Estimated): January 31, 2027
• Last Updated: January 23, 2026

Record last verified: 2026-01

Locations

US (1)