Genetically Modified T-Cells + Aldesleukin for Melanoma

RN
Overseen ByRodabe N. Amaria, MD
Age: Any Age
Sex: Any
Trial Phase: Phase 1
Sponsor: M.D. Anderson Cancer Center
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?

This trial aims to determine the optimal dose and assess the side effects of using genetically modified T-cells and aldesleukin (a type of immunotherapy) to treat stage III-IV melanoma, a type of skin cancer. The treatment involves altering T-cells (a kind of white blood cell) in a lab to enhance their ability to fight melanoma cells when reintroduced into the body. Aldesleukin boosts the T-cells' capacity to attack cancer. Suitable candidates for this trial have stage III or IV melanoma that has spread to other parts of the body. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to be among the first to receive this new therapy.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on steroid therapy or have used systemic steroids recently, you may need to stop, as these are generally not allowed except for low-dose prednisone. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that specially modified T-cells, such as NGFR-transduced autologous T lymphocytes, have been safely used in patients with melanoma. These treatments can lead to strong responses against cancer. In the lab, these T-cells, a type of white blood cell, are altered to better locate and attack cancer cells.

Aldesleukin, also known as Proleukin, is another component of this treatment. Since 1998, it has been used to treat metastatic melanoma, an advanced form of skin cancer that has spread. Although it can cause serious side effects, the FDA has approved it, indicating that its safety is well understood. During trials, some patients experienced severe reactions, but these are well-documented and monitored.

Both components of this treatment have been studied for safety in people with advanced melanoma. Despite the risks, these treatments are not new and have been used in other patients with similar conditions.12345

Why do researchers think this study treatment might be promising for melanoma?

Researchers are excited about the potential of NGFR-transduced autologous T lymphocytes for treating melanoma because this approach uses genetically modified T-cells to specifically target cancer cells. Unlike standard treatments like chemotherapy or immune checkpoint inhibitors, this therapy involves engineering a patient's own T-cells to enhance their cancer-fighting abilities. By combining these modified T-cells with high-dose aldesleukin, a drug that boosts immune activity, the treatment aims to create a more potent and targeted attack on melanoma cells. This innovative method offers hope for improved outcomes by harnessing the body's own immune system in a novel way, potentially leading to more effective and personalized cancer care.

What evidence suggests that genetically modified T-cells followed by aldesleukin might be an effective treatment for melanoma?

Research shows that specially modified T-cells, such as NGFR-transduced autologous T lymphocytes, effectively treat melanoma. This treatment, part of the current trial, involves tumor-infiltrating lymphocyte (TIL) therapy, which has been approved for melanoma and has proven effective. Participants in this trial will receive these modified T-cells combined with aldesleukin, a drug that boosts white blood cells. Studies indicate that aldesleukin can enhance T-cells' ability to fight melanoma and has helped shrink or slow tumor growth in 5–27% of patients with advanced melanoma. These findings suggest that this combination could be a promising treatment for advanced melanoma.26789

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?

This trial is for adults with stage III-IV melanoma who have adequate lung function, no severe psychiatric diseases, and are not pregnant or nursing. Participants must not have had recent cancer treatments, organ transplants, significant medical illnesses, or be on chronic steroids. They need measurable melanoma lesions suitable for T-cell generation and agree to use birth control.

Inclusion Criteria

I have been active and mostly self-sufficient in the last month.
I had a brain scan within the last 30 days.
My melanoma has spread or is in stage III.
See 20 more

Exclusion Criteria

I haven't had cancer treatment or specific inhibitors in the last 4 weeks/7 days.
Presence of a significant psychiatric disease, which in the opinion of the principal investigator or his designee, would prevent adequate informed consent
Active systemic infections requiring intravenous antibiotics, coagulation disorders or other major medical illnesses of the cardiovascular, respiratory or immune system; PI or his designee shall make the final determination regarding appropriateness of enrollment
See 9 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Chemotherapy

Patients receive cyclophosphamide and fludarabine phosphate intravenously to prepare for T-cell infusion

1 week
Daily visits for 5 days

T-Cell Infusion and Aldesleukin Treatment

Patients receive TGFb DNRII-transduced autologous TIL and NGFR-transduced autologous T lymphocytes followed by high-dose aldesleukin

5 days
Inpatient stay for monitoring and treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 weeks
Visits at 6 and 12 weeks, then every 3 months for 1 year, and yearly for 10 years

What Are the Treatments Tested in This Trial?

Interventions

  • Aldesleukin
  • NGFR-transduced Autologous T Lymphocytes
Trial Overview The trial tests genetically modified T-cells designed to target melanoma followed by aldesleukin (a substance that can boost the immune system). It aims to find the best dose and observe side effects. The process involves modifying patients' own T-cells in a lab before reintroducing them into their bodies.
How Is the Trial Designed?
1Treatment groups
Experimental Treatment
Group I: Treatment (chemotherapy, autologous T-cell immunotherapy)Experimental Treatment6 Interventions

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+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Citations

Update on use of aldesleukin for treatment of high-risk ...The 6-month progression-free survival benefit is indicative of the ability of melanoma to develop resistance, and studies have shown that BRAF-mutated melanoma ...
The High-Dose Aldesleukin “Select” Trial - PubMed CentralEfficacy Data. The objective response rate of all 120 patients to HD IL-2 confirmed by independent review was 25% (95% CI, 17.5 to 33.7 ...
Single-agent interleukin-2 in the treatment of metastatic ...Data from three randomized controlled trials demonstrate that single-agent interleukin-2, when given in high-doses, elicited objective response rates of 5–27% ...
Current Status of Interleukin-2 Therapy for Metastatic Renal ...Interleukin-2 (IL-2, Proleukin) is one of the most effective agents in the treatment of metastatic renal cell carcinoma and metastatic melanoma.
Single-institution Outcome of High-dose Interleukin-2 (HD ...Results: Fifteen patients with metastatic melanoma had been treated with HD IL-2. There were 4 patients exhibiting some response, with 1 complete response (CR), ...
Proleukin (aldesleukin) injection label - accessdata.fda.govThe rate of drug-related deaths in the 255 metastatic RCC patients who received single- agent Proleukin® (aldesleukin) was 4% (11/255); the rate of drug-related ...
HIGHLIGHTS OF PRESCRIBING INFORMATION ...Proleukin is indicated for the treatment of adults with metastatic melanoma. ... The safety of Proleukin was evaluated in a series of single and multicenter ...
Aldesleukin (Proleukin) - Medical Clinical Policy BulletinsProleukin is indicated for the treatment of adults with metastatic melanoma. Compendial Uses. Unresectable cutaneous melanoma; Chronic graft-versus-host disease ...
A retrospective analysis of high-dose aldesleukin (HD IL-2) ...Background: HD IL-2 received FDA-approval for the front-line treatment for MM and mRCC based on its ability to produce durable responses in a ...
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