21 Participants Needed

Engineered TILs + Acetazolamide for Melanoma

Rodabe N. Amaria profile photo
Overseen ByRodabe N. Amaria
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of this clinical research study is to find the recommended dose of OBX-115 in combination with acetazolamide that can be given to patients with metastatic melanoma previously treated with immune checkpoint inhibitors. The safety and tolerability of the study drug combination will also be studied.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you cannot be on chronic steroid therapy above 10 mg/day of prednisone or its equivalent, and you must not have had chemotherapy or certain targeted therapies within 2 weeks before starting the trial.

Is the treatment of Engineered TILs + Acetazolamide for Melanoma generally safe in humans?

The safety of engineered T cells, like those used in TIL therapy, has been studied, showing potential risks such as severe cytokine release syndrome (a severe immune reaction) and neurotoxicity (nerve damage). These risks highlight the importance of careful monitoring and management during treatment.12345

What makes the treatment OBX-115 unique for melanoma?

OBX-115 is unique because it involves engineered tumor-infiltrating lymphocytes (TILs) that are modified to enhance their ability to target and kill melanoma cells, potentially offering a more effective approach than traditional therapies. This treatment also includes the use of acetazolamide, which may help improve the effectiveness of the TILs by modifying the tumor environment.12678

What data supports the effectiveness of the treatment Engineered TILs + Acetazolamide for Melanoma?

Research shows that adoptive T-cell therapy using tumor-infiltrating lymphocytes (TIL) has achieved clinical response rates of 50% or more in metastatic melanoma patients, indicating its potential effectiveness. Additionally, gene-modified T-cells with enhanced properties have shown promising results in preclinical models, suggesting potential benefits for melanoma treatment.167910

Who Is on the Research Team?

Rodabe N. Amaria | MD Anderson Cancer ...

Rodabe N. Amaria

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

Adults over 18 with stage III or IV metastatic melanoma that's not removable by surgery and have failed immune checkpoint inhibitor therapy can join. They need a tumor for TIL generation, another for response assessment, proper organ function tests, no severe heart issues, and must use birth control. Excluded are those with uncontrolled illnesses, recent chemotherapy or live vaccines, certain infections like HIV/HCV requiring treatment, brain metastases of melanoma, serious cardiac conditions within the last 6 months, other cancers in the last 2 years (with exceptions), significant allergies to sulfa drugs or on chronic acetazolamide.

Inclusion Criteria

Within 7 days of tumor harvest and within 7 days of initiating lymphodepletion, patients must meet the following laboratory criteria: ANC ≥ 1000/mm3, Hemoglobin ≥ 8.0 g/dL (transfusion allowed), Platelet count ≥ 75,000/mm3, ALT/SGPT and AST/SGOT ≤ 2.5 x the upper limit of normal (ULN), Patients with liver metastases may have liver function tests (LFT) ≤ 5.0 x ULN, Calculated creatinine clearance (Cockcroft-Gault) ≥ 50.0 mL/min, Total bilirubin ≤ 1.5 X ULN, Negative serum pregnancy test (female patients of childbearing potential), 12-lead electrocardiogram (EKG) showing no active ischemia and Fridericia's corrected QT interval (QTcF) less than 480 ms, Echocardiogram showing no evidence of congestive heart failure (as defined by New York Heart Association Functional Classification III or IV) or LVEF <50%, Women of child-bearing potential (WCBP) must have a negative serum pregnancy test prior to treatment, Patients must have agreed to use effective methods of birth control throughout the study, Patient (or legally authorized representative) has voluntarily agreed to participate in the study by providing signed and dated informed consent (ICF) in accordance with International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines and applicable local regulations, Patient has agreed to abide by all protocol required procedures including study related assessments, and management by treating institution for the duration of the study and long-term follow-up (LTFU), Patients who have received bridging therapy between time of TIL harvest and initiation of lymphodepletion must meet all required clinical, laboratory and imaging criteria in order to qualify for therapy initiation, Lesions amenable to radiotherapy or palliative radiotherapy should be treated > 4 weeks prior to enrollment and subjects must be fully recovered from the effects of radiation. However, palliative radiation is permitted if subjects recover from all side effects to ≤ Grade 1 toxicities (based on CTCAE, v.5)
I am fully active or can carry out light work.
I have advanced melanoma with tumors that can be used to generate TILs and at least one tumor for tracking treatment response.
See 1 more

Exclusion Criteria

Patients who are pregnant or breastfeeding
I have not used immune checkpoint inhibitors as a temporary treatment.
I do not have a fever or an active infection needing treatment.
See 18 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Participants receive chemotherapy to prepare the body for the study drug combination

2-3 weeks

Treatment

Participants receive OBX-115 and acetazolamide to assess safety, tolerability, and preliminary efficacy

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

  • Acetazolamide
  • OBX-115
Trial Overview This Phase I trial is testing OBX-115 combined with acetazolamide to find a safe dose for patients with metastatic melanoma who've already tried immune checkpoint inhibitors. It also includes pre-treatment drugs like cyclophosphamide and fludarabine phosphate to prepare the body ('lymphodepletion') before introducing OBX-115.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: OBX-115 plus AcetazolamideExperimental Treatment6 Interventions
Participants will receive chemotherapy to prepare your body for the study drug combination, then you will receive OBX-115 and acetazolamide.

Find a Clinic Near You

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials
3,107
Recruited
1,813,000+

Published Research Related to This Trial

A new GMP protocol has been developed to produce T-cell receptor (TCR) gene-modified T-cells with an early memory phenotype, which may enhance their effectiveness in recognizing and attacking cancer cells.
These T-cells, generated using a combination of anti-CD3/CD28 stimulation and expansion with IL-7 and IL-15, are now being tested in a phase I/IIa clinical trial for advanced melanoma, marking a novel approach in T-cell therapy.
Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype.Gomez-Eerland, R., Nuijen, B., Heemskerk, B., et al.[2021]
In a study involving 16 healthy donors, researchers found that using specific activation conditions (soluble anti-CD3/CD28 mAbs with IL15 and IL21) improved the quality and function of gene-modified T cells, which is crucial for effective cancer treatment.
These optimized T cells showed better binding to target molecules and a more favorable phenotype, suggesting that these methods could enhance the efficacy of CAR and TCR therapies in future clinical trials for patients with certain tumors.
T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness.Lamers, CH., van Steenbergen-Langeveld, S., van Brakel, M., et al.[2018]
The study developed optimized CAR T cells targeting TAG72, showing that the CD28 transmembrane domain enhances anti-tumor activity and IFNγ secretion, which is crucial for effective treatment of solid tumors like advanced ovarian cancer.
In preclinical models, CAR T cells expressing a membrane-bound IL-12 (mbIL12) significantly improved T cell proliferation and tumor cell killing, leading to strong anti-tumor responses and better T cell persistence, suggesting a promising approach for enhancing CAR T cell therapies in clinical settings.
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting.Jun Lee, EH., Cullen, C., Murad, JP., et al.[2023]

Citations

Manufacture of gene-modified human T-cells with a memory stem/central memory phenotype. [2021]
White paper on adoptive cell therapy for cancer with tumor-infiltrating lymphocytes: a report of the CTEP subcommittee on adoptive cell therapy. [2020]
T cell receptor-engineered T cells to treat solid tumors: T cell processing toward optimal T cell fitness. [2018]
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting. [2023]
Cardiovascular toxicity and titin cross-reactivity of affinity-enhanced T cells in myeloma and melanoma. [2023]
[Next generation engineered T cells for cell therapy: from lymphoma to solid tumors]. [2019]
Identification of a Titin-derived HLA-A1-presented peptide as a cross-reactive target for engineered MAGE A3-directed T cells. [2023]
Improving the efficacy and safety of engineered T cell therapy for cancer. [2020]
Cross-study safety analysis of risk factors in CAR T cell clinical trials: An FDA database pilot project. [2022]
Antigen-dependent IL-12 signaling in CAR T cells promotes regional to systemic disease targeting. [2023]
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