A Phase 1b / 2 Drug Resistant Immunotherapy With Activated, Gene Modified Allogeneic or Autologous γδ T Cells (DeltEx) in Combination With Maintenance Temozolomide in Subjects With Recurrent or Newly Diagnosed Glioblastoma

Study Purpose

This multicenter, Phase 1b/2 study is being conducted to determine if the experimental cell therapy is safe, tolerable and can delay the return of cancer in patients with a newly diagnosed or recurrent glioblastoma multiforme (GBM) in combination with standard chemotherapy treatment temozolomide (TMZ). If there is a 25% or greater improvement in survival in this study then the therapy should be studied further.

Recruitment Criteria

Accepts Healthy Volunteers

Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms

No
Study Type

An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes.


An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes.


Searching Both is inclusive of interventional and observational studies.

Interventional
Eligible Ages 18 Years and Over
Gender All
More Inclusion & Exclusion Criteria

Inclusion Criteria:

  • - Subjects with histologically or cytologically confirmed history of IDH-wild type glioblastoma.
  • - Phase 1b and Arm B of Phase 2: Subjects must have completed no more than one standard therapy for glioblastoma, have received no prior Avastin® therapy (unless solely used for edema management) and be eligible for resection.
  • - Arms A and C: Subjects must have newly diagnosed, treatment naïve glioblastoma.
  • - Phase 1b and Arm B and Arm C: Subjects must have a partially matched haploidentical or matched related donor.
  • - Subjects with magnetic resonance imaging (MRI) features consistent with and suspicious for recurrent malignant glioma in Phase 1b and Arm B.
  • - Agreeable to inserting and maintaining a Rickham catheter.
  • - ≥ 18 years of age.
  • - Karnofsky Performance Status ≥ 70% - Female subjects of childbearing potential must have a negative urine/serum pregnancy test within 72 hours of study enrollment.
Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free of menses for > 2 years.
  • - Male subjects and their female partners and female subjects of childbearing potential must be willing to use a combination of two methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study.

Exclusion Criteria:

  • - Subject in Arm A or donor from Phase 1b, Arms B, and Arm C received vaccinations within 4 weeks or underwent surgery (major or minor) within 72 hours before leukapheresis collection.
  • - Cellular immunotherapy or gene therapy or within six weeks prior to entering the study, surgical resection or alkylating agent chemotherapy within four weeks prior to entering the study, receiving tumor treating fields (TTF) Optune therapy, or have received experimental immunotherapy at any time.
  • - Subjects receiving any other investigational agents concurrently while on study.
  • - Have not recovered from adverse events (≤ Grade 1) from previously administered therapy.
Subjects with alopecia unless of immune origin are an exception to this criterion and may qualify for this study.
  • - Have received prior treatment with an allogeneic therapy, including bone marrow or solid tumor transplant.
  • - Concurrent malignancy or an active second malignancy.
Subjects with a history of second malignancy must have no evidence of cancer for two years prior to enrolment or have a surgically cured cancer with low risk of recurrence to enroll. Discuss with medical monitor prior to enrolment.
  • - Contraindication to the placement of an intracranial access device (Rickham catheter) at the time of surgery.
  • - Prior history of encephalitis, multiple sclerosis, or other CNS infection <1 year prior to glioblastoma diagnosis.
  • - Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, or any other medical condition that precludes surgery.
Also, medical/surgical/psychiatric illness/social situations that would limit compliance with study requirements or confound interpretation of safety and efficacy data. Subjects with a history of seizure as a result of their glioblastoma must be seizure free and on appropriate anti-epileptic medication for 3 weeks prior to dosing with the investigational agent.
  • - Allergies/hypersensitivity to amino bisphosphonates such as Zoledronate®, Pamidronate® or similar.
  • - History of HIV or active hepatitis even if well controlled or history of an autoimmune condition.

Trial Details

Trial ID:

This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.

NCT05664243
Phase

Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans.

Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data.

Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs.

Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.

Phase 1/Phase 2
Lead Sponsor

The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.

In8bio Inc.
Principal Investigator

The person who is responsible for the scientific and technical direction of the entire clinical study.

Louis B Nabors, MD
Principal Investigator Affiliation University of Alabama at Birmingham
Agency Class

Category of organization(s) involved as sponsor (and collaborator) supporting the trial.

Industry
Overall Status Recruiting
Countries United States
Conditions

The disease, disorder, syndrome, illness, or injury that is being studied.

Glioblastoma
Additional Details

This is a Phase 1b and 2 open-label cellular therapy trial using genetically modified gamma-delta (γδ) T cells or DeltEx Drug Resistant Immunotherapy (DRI). Gamma-delta T cells are a type of immune cell that may help the immune system recognize and kill cancer cells. The cells have been modified to make them resistant to the killing effects of chemotherapy such that they may be administered in combination with chemotherapy without being destroyed. The chemotherapy that is being used in this study is called temozolomide (TMZ) which is the standard-of-care used to treat glioblastoma patients. The DRI cells are given in combination with a standard dose of TMZ and are administered through a catheter directly into the brain where the tumor is located. There are four arms to this study for eligible subjects with either newly diagnosed or relapsed IDH wild-type (IDH-wt) glioblastoma (GBM). Arm A will enroll newly diagnosed glioblastoma subjects to receive DRI cells derived from their own cells (autologous). The Phase 1b, Arms B and C will enroll subjects to receive DRI cells derived from a donor's cells (allogeneic). Subjects in the Phase 1b portion and Arm B must have relapsed disease, that is disease that has returned after initial treatment, while Arm A and C subjects must have newly diagnosed disease. Prescreening subjects will have a standard-of-care surgical resection of their tumor. Once their preliminary eligibility is confirmed, they will have a Rickham catheter placed which is a device typically used to deliver chemotherapy into the brain that will be used to deliver the DRI cells directly to the tumor. Following the surgical resection, subjects in Arm A will return to the study doctor's office/clinic to undergo a procedure called an apheresis. This procedure will isolate the immune cells from the blood to help make the DRI product for the subject. These cells include the gamma-delta T cells that will be used to make the DRI cells. Once the cells for the DRI product are made, they are frozen and stored for future use. In the Phase Ib and Arms B and C of the trial, a donor will undergo apheresis to provide the source of cells for the DRI product. Following apheresis and confirmation that the required number of gamma-delta T cells were successfully collected; subjects in Arm A and C will begin the recommended or standard-of-care treatment for newly diagnosed GBM. This will include six weeks of chemotherapy with TMZ and radiation. Subjects will then have about a four week break prior to beginning the maintenance phase of treatment. Maintenance therapy includes five days of chemotherapy, every 28 days, which is repeated for six cycles. The previously frozen DRI product is thawed, prepared and is infused on the first day of each five-day cycle through the Rickham catheter. Subjects received a total of 6 infusions. Subjects in the Phase Ib and Arm B will only receive one dose of TMZ along with the DRI product every 28 days for a total of six cycles. Subjects will be observed for a of minimum 30 days after receiving the first dose of the DRI gamma-delta T cells. Subjects will be followed for potential side effects. The approximate duration of the study may be up to 15 years, or until disease progression or subjects withdraw from the study.

Arms & Interventions

Arms

Experimental: 1) Autologous: Phase 2 Arm A

Arm A subjects with newly diagnosed disease will receive autologously derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Experimental: 2) Allogeneic: Phase 1b

Phase 1b subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Experimental: 3) Allogeneic: Phase 2 Arm B

Arm B subjects with relapsed disease will have allogeneic derived, genetically modified gamma-delta T cells administered with temozolomide

Experimental: 4) Allogeneic: Phase 2 Arm C

Arm C subjects with newly diagnosed disease will receive allogeneic derived, genetically modified gamma-delta T cells administered with maintenance temozolomide.

Interventions

Biological: - Autologous genetically modified gamma-delta T cells

Arm A: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with TMZ maintenance

Biological: - Allogeneic genetically modified gamma-delta T cells

Phase 1b and Arm B: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with D1 of TMZ 150mg/m2 Arms C: Cells will be administered on Day 1 of each of 6, 28-day cycles in combination with TMZ maintenance

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

University of Alabama at Birmingham, Birmingham, Alabama

Status

Not yet recruiting

Address

University of Alabama at Birmingham

Birmingham, Alabama, 35294

UC San Diego Moores Cancer Center, La Jolla, California

Status

Recruiting

Address

UC San Diego Moores Cancer Center

La Jolla, California, 92093

Site Contact

Sheila Medina-Torne

[email protected]

1-646-933-5607

UCLA, Los Angeles, California

Status

Recruiting

Address

UCLA

Los Angeles, California, 90024

Site Contact

Savanah Wiles

[email protected]

310-825-5321

Moffitt Cancer Center, Tampa, Florida

Status

Recruiting

Address

Moffitt Cancer Center

Tampa, Florida, 33612

Site Contact

Jessica Malka

[email protected]

813-745-0854

Louisville, Kentucky

Status

Recruiting

Address

University of Louisville Hospital/James Graham Brown Cancer Center

Louisville, Kentucky, 40202

Site Contact

Akshitkumar Mistry, MD

[email protected]

1-646-933-5607

Cleveland Clinic, Cleveland, Ohio

Status

Recruiting

Address

Cleveland Clinic

Cleveland, Ohio, 44195

Site Contact

Elicia Mangan

[email protected]

216-636-2436

Columbus, Ohio

Status

Recruiting

Address

Ohio State University Wexner Medical Center- James Cancer Center

Columbus, Ohio, 43210

Site Contact

Amy Heider

[email protected]

614-685-9574

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