Adoptive Cell Transfer + Interleukin 2 for Cancer

Recruiting in Palo Alto (17 mi)

Overseen by Gregory Daniels, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Recruiting

Sponsor: Gregory Daniels

Must be taking: Interleukin-2

Must not be taking: Immune suppressants

Disqualifiers: Pregnancy, Infections, Heart disease, others

No Placebo Group

Trial Summary

What is the purpose of this trial?

To determine whether special tumor fighting cells that is taken from participants' tumors and grown in the laboratory and then given back to the participant will fight the participant's cancer when their immune system is suppressed from attacking these special tumor fighting cells. This is called transfer of autologous (they came from you) tumor infiltrating lymphocytes (the cells that have been grown in the laboratory. Participants getting these cell infusions will also be treated with interleukin-2 (IL-2).

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, it mentions that more than four weeks must have passed since any prior systemic therapy, and six weeks since any anti-CTLA4 therapy, suggesting a possible need to pause certain treatments.

What data supports the effectiveness of this treatment?

Research shows that adoptive cell therapy using tumor-infiltrating lymphocytes (TIL) combined with interleukin-2 (IL-2) can lead to significant tumor responses in patients with metastatic melanoma, with response rates up to 52%. Additionally, some studies have reported objective tumor responses in patients with renal cell carcinoma and melanoma, lasting from 3 to 14 months. ^{1 2 3 4 5}

Is Adoptive Cell Transfer with Interleukin 2 safe for humans?

Adoptive Cell Transfer with Interleukin 2 has been studied in patients with advanced cancers, primarily melanoma, and while it shows promise in treating cancer, it is associated with significant side effects, especially when high doses of Interleukin 2 are used. These side effects can be severe but are usually temporary, and efforts are being made to reduce them by using lower doses of Interleukin 2. ^{1 3 4 6 7}

How is the treatment with autologous tumor infiltrating lymphocytes and interleukin-2 different from other cancer treatments?

This treatment is unique because it uses a patient's own immune cells (tumor-infiltrating lymphocytes) that are grown and activated outside the body, then reinfused to fight cancer, combined with interleukin-2 to boost the immune response. Unlike standard treatments, it specifically targets the patient's tumor cells and can lead to long-lasting responses, although it may have significant side effects due to the high-dose interleukin-2. ^{1 2 3 4 5}

Research Team

Ezra Cohen, MD

Principal Investigator

University of California, San Diego

Gregory Daniels, MD

Principal Investigator

University of California, San Diego

Eligibility Criteria

This trial is for adults with advanced melanoma or head and neck cancers that can't be removed by surgery, have progressed after treatment, and are not candidates for curative therapy. They must have a life expectancy over 3 months, no HIV or hepatitis B/C, good organ function, and an ECOG status of 0-1 (fully active to restricted in physically strenuous activity). Pregnant women and those with primary immunodeficiency or certain heart conditions cannot participate.

Inclusion Criteria

My head or neck cancer has returned or spread.

It has been over four weeks since my last systemic therapy.

I have up to 3 brain metastases that are stable and treated if needed.

Exclusion Criteria

I have a condition that significantly weakens my immune system.

I need medication to suppress my immune system, including steroids.

I am pregnant or breastfeeding.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Lymphodepletion

Participants undergo lymphodepletion to suppress the immune system before cell transfer

1-2 weeks

Adoptive Cell Transfer

Participants receive infusions of autologous tumor infiltrating lymphocytes and high-dose interleukin-2

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Autologous Tumor Infiltrating Lymphocytes (CAR T-cell Therapy)
• High-Dose Interleukin 2 (Cytokine)

Trial Overview The study tests if tumor fighting cells from the patient's own tumors can combat cancer when reintroduced into their body alongside high-dose interleukin-2 (IL-2), which supports immune response. This adoptive cell transfer aims to see if these lab-grown cells help fight the cancer more effectively.

Participant Groups

Group I: melanoma Experimental Treatment 2 Interventions

Group II: head and neck cancer Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Gregory Daniels

Lead Sponsor

Trials

2

Recruited

30+

Immunotherapy Foundation

Collaborator

Trials

1

Recruited

20+

Findings from Research

In a phase I/II trial involving 25 patients with treatment-refractory metastatic melanoma, adoptive cell transfer therapy using tumor-infiltrating lymphocytes (TIL) combined with a lower-dose IL2 regimen resulted in a 42% overall response rate, including three complete responses and seven partial responses.

The study demonstrated that while some classical IL2-related toxicities occurred, they were manageable outside of intensive care, suggesting that this attenuated IL2 approach may enhance safety while still achieving significant clinical efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. Andersen, R., Donia, M., Ellebaek, E., et al.[2021]

In a study involving 28 patients with various cancers, including malignant melanoma and renal cell carcinoma, treatment with autologous expanded tumor-infiltrating lymphocytes (TIL) combined with interleukin-2 resulted in objective tumor responses in 29% of renal cell cancer patients and 23% of melanoma patients, lasting between 3 to 14 months.

The treatment was associated with limited toxic side effects, and notably, no patients required intensive-care monitoring, suggesting a favorable safety profile for this immunotherapy approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Kradin, RL., Kurnick, JT., Lazarus, DS., et al.[2020]

Adoptive cell therapy using autologous tumor infiltrating lymphocytes (TIL) has shown promising results, with objective response rates of up to 52% in patients with advanced metastatic melanoma.

The treatment involves activating and expanding TILs outside the body before re-infusing them into the patient, followed by administration of Interleukin-2 (IL-2) to enhance the immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Key Factors in Clinical Protocols for Adoptive Cell Therapy in Melanoma. Considine, B., Hurwitz, ME.[2023]

In a pilot study involving 6 patients with metastatic melanoma, the combination of tumor-infiltrating lymphocyte (TIL) therapy and low-dose IL-2 injections resulted in significant reductions in treatment-related toxicity, with no severe adverse events reported.

The treatment led to objective clinical responses in 2 patients, with ongoing complete responses lasting over 10 months, suggesting that low-dose IL-2 can enhance the safety and efficacy of adoptive cell therapy for melanoma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. Ellebaek, E., Iversen, TZ., Junker, N., et al.[2021]

In a study involving 69 patients with metastatic melanoma, unselected young tumor-infiltrating lymphocytes (TILs) showed a higher response rate (35%) compared to CD8(+)-enriched TILs (20%), although the difference was not statistically significant.

The research suggests that unselected young TILs may be more effective and easier to prepare than CD8(+)-enriched TILs, as the latter did not demonstrate superior therapeutic potency despite being more complex to produce.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. Dudley, ME., Gross, CA., Somerville, RP., et al.[2021]

In a study involving 21 cancer patients, tumor-infiltrating lymphocytes (TIL) were successfully activated with interleukin 2 (IL-2) and showed significant tumor-killing activity, leading to complete regression of malignant pleural effusions in one pancreatic cancer patient and nearly complete regression of malignant ascites in a gastric cancer patient.

The optimal concentration of IL-2 for maximizing TIL proliferation and tumor-killing ability was found to be 1,500 IU/ml, demonstrating that adoptive transfer of activated TIL can be an effective immunotherapy approach in treating certain cancers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes]. Yamaue, H., Tanimura, H., Tsunoda, T., et al.[2011]

Adoptive cell therapy using autologous tumor-infiltrating lymphocytes (TIL) combined with high-dose interleukin-2 (IL-2) showed promising results, with 50% of refractory metastatic melanoma patients experiencing tumor regression, highlighting its efficacy.

The modified 'Young'-TIL protocol, which uses minimally cultured T cells without extensive selection, resulted in a higher patient retention rate and better clinical responses compared to the 'Selected'-TIL protocol, suggesting it may be a more feasible and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. Besser, MJ., Shapira-Frommer, R., Treves, AJ., et al.[2013]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-Lasting Complete Responses in Patients with Metastatic Melanoma after Adoptive Cell Therapy with Tumor-Infiltrating Lymphocytes and an Attenuated IL2 Regimen. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. [2020]

3. United States pubmed.ncbi.nlm.nih.gov

Key Factors in Clinical Protocols for Adoptive Cell Therapy in Melanoma. [2023]

4. England pubmed.ncbi.nlm.nih.gov

Adoptive cell therapy with autologous tumor infiltrating lymphocytes and low-dose Interleukin-2 in metastatic melanoma patients. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Randomized selection design trial evaluating CD8+-enriched versus unselected tumor-infiltrating lymphocytes for adoptive cell therapy for patients with melanoma. [2021]

6. Japan pubmed.ncbi.nlm.nih.gov

[Clinical application of adoptive immunotherapy by cytotoxic T lymphocytes induced from tumor-infiltrating lymphocytes]. [2011]

7. United States pubmed.ncbi.nlm.nih.gov

Minimally cultured or selected autologous tumor-infiltrating lymphocytes after a lympho-depleting chemotherapy regimen in metastatic melanoma patients. [2013]