Natural Killer Cell Therapy (UD TGFbetai NK Cells) and Temozolomide for the Treatment of Stage IV Melanoma Metastatic to the Brain

NCT05588453 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: OSU-21101NCI-2021-14033
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial tests the safety, side effects, and best dose of universal donor UD TGFbetai natural killer (NK) cells, and whether UD TGFbetai NK cells with temozolomide works to shrink tumors in patients with stage IV melanoma that has spread to the brain (metastatic to the brain). NK cells are immune cells that contribute to anti-tumor immunity by recognizing and destroying transformed or stressed cells. Temozolomide is in a class of medications called alkylating agents. It works by slowing or stopping the growth of cancer cells in the body. Giving UD TGFbetai NK cell and temozolomide may work better in treating patients with stage IV melanoma.

Conditions

Metastatic Malignant Neoplasm in the Brain; Metastatic Melanoma; Pathologic Stage IV Cutaneous Melanoma AJCC v8; Clinical Stage IV Cutaneous Melanoma AJCC v8

Outcome Measures

Primary Outcomes (3)

• Dose limited toxicities (Phase I)

  Toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE) criteria, version 4.03. The CTCAE provides descriptive terminology and a grading scale for each adverse event listed. All toxicities will be summarized as the percentage of patients experiencing each type and grade of event according to dose level.

  Up to 28 days

• Incidence of adverse events (AEs) (Phase I)

  Assessed using CTCAE version (V)4.0. All toxicities will be summarized as the percentage of patients experiencing each type and grade of event according to dose level. Patients who receive at least one dose of treatment will be included in the analysis. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns.

  Up to 5 years

• Proportion of subjects who achieve an intracranial complete response or partial response (Phase II)

  Assessed using modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria.

  Up to 5 years

Secondary Outcomes (6)

• Incidence of adverse events of universal donor (UD) TGFbetai natural killer (NK) cells when delivered with temozolomide as a lymphodepleting agent (Phase I)

  Up to 5 years

• Extracranial response rate (Phase II)

  Up to 5 years

• Progression free survival (PFS) (intracranial, extracranial, overall) (Phase II)

  From initiation of therapy to the time of Response Evaluation Criteria in Solid Tumors (RECIST) progression or death, assessed up to 5 years

• Overall Survival (OS) (Phase II)

  From initiation of therapy to death, assessed up to 5 years

• Percentage of patients with adverse events of the combination temozolomide and UD TGFbetai NK cells (Phase II)

  Up to 5 years

Other Outcomes (4)

• Phenotype and function of the UD TGFbetai NK cells

  Up to 5 years

• Persistence of UD TGFbetai NK cells

  Up to 5 years

• Distribution of UD TGFbetai NK cells in the cerebrospinal fluid (CSF)

  Up to 5 years

Study Arms (1)

Treatment (UD TGFbetai NK cells, temozolomide)

EXPERIMENTAL

Patients receive UD TGFbetai NK cells IV over 30 minutes on day 1 and temozolomide PO daily on days 1-5. Treatment with UD TGFbetai NK cells repeats every 28 days for up to 3 cycles in the absence of disease progression or unacceptable toxicity. Cycles of temozolomide repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Biological: Natural Killer Cell Therapy; Drug: Temozolomide

Interventions

Natural Killer Cell Therapy BIOLOGICAL

Given UD TGFbi NK cell IV

Treatment (UD TGFbetai NK cells, temozolomide)

Temozolomide DRUG

Given PO

Also known as: CCRG-81045, Imidazo[5,1-d]-1,2,3,5-tetrazine-8-carboxamide, 3, 4-dihydro-3-methyl-4-oxo-, M & B 39831, M and B 39831, Methazolastone, RP-46161, SCH 52365, Temcad, Temodal, Temodar, Temomedac, TMZ

Treatment (UD TGFbetai NK cells, temozolomide)

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed melanoma with stage IV disease
• Radiologically confirmed brain metastasis (n \>= 1) with at least one measurable central nervous system (CNS) lesion \>= 10 mm on T1-weighted gadolinium enhanced magnetic resonance imaging (MRI) and unequivocal evidence of progression
• No indication for stereotactic radiotherapy
• At least 4 weeks from any anticancer treatment (cytotoxic chemotherapy, signal transduction inhibitors, immunotherapy or radiation)
• Absolute neutrophil count (ANC) 1 x 10\^9/L
• Platelets \> 100,000/L
• Hemoglobin (Hgb) \>= 10 g/dL
• Creatinine =\< 1.5 x upper limit of normal (ULN)
• Albumin \>= 2.5 g/dL
• Serum bilirubin \< 1.5 x ULN unless due to Gilbert's syndrome
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 5 x ULN if documented liver metastases or \< 3 X ULN without liver metastasis
• \> 18 years old (y/o)
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• Females of reproductive age must agree to the use of an effective contraceptive method while on treatment, beginning 2 weeks before the first dose of investigational product and for 28 days after the final dose of investigational product for women. Males able to father a child must practice adequate methods of contraception or completely abstain from intercourse from the first dose of investigational treatment until one week after the final dose of investigational treatment
• Women of childbearing potential must have a negative serum pregnancy test within 14 days of enrollment and/or urine pregnancy test 48 hours prior to the administration of the first study treatment

You may not qualify if:

• Planned or concurrent systemic treatment or radiation therapy
• If requiring corticosteroids for cerebral edema, patients must be on a stable dose. Lowest dose of steroids needed to control CNS edema is recommended. Doses above 4 mg daily need to be cleared by principal investigator (PI) of the study
• Known contra-indication to MRI
• Patients with non-melanoma malignancies are excluded unless a complete remission has been achieved at least 3 years prior to study entry and no additional therapy is required or anticipated during the study period (exceptions include: non-melanoma skin cancers, in situ bladder cancer, in situ gastric cancer, in situ colon cancers, in situ cervical cancers/dysplasia, or in situ breast carcinoma)
• Patients with other concurrent severe and/or uncontrolled medical disease which could compromise participation in the study, such as:
• Active infection
• Current active hepatic or renal disease
• Pregnant women, women who are likely to become pregnant or are breastfeeding
• Patients with significantly altered mental status prohibiting the understanding of the study or with psychological, familial, sociological, or geographical conditions potentially hampering ability to consent, compliance with the study protocol, and follow-up schedule; those conditions should be discussed with the patient before remigration in the trial
• Patients who received any other investigational drugs within the 30 days prior to screening visit
• Leptomeningeal metastases diagnosed by MRI
• If steroids are necessary to control symptoms related to CNS metastases, patients should be on the lowest dose of steroids necessary to control symptoms

Sponsors & Collaborators

• Kari Kendra: lead

Study Sites (1)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

Related Links

• The Jamesline

MeSH Terms

Conditions

Brain Neoplasms; Melanoma

Interventions

Temozolomide

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Dacarbazine; Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kari L Kendra, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

The Ohio State University Comprehensive Cancer Center

CONTACT

800-293-5066; OSUCCCClinicaltrials@osumc.edu

Study Design

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

Study Record Dates

• First Submitted: September 5, 2022
• First Posted: October 20, 2022
• Study Start: March 1, 2023
• Primary Completion: April 15, 2026
• Study Completion: April 15, 2026
• Last Updated: January 12, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)