Metastatic Malignant Neoplasm in the LiverPhase 1NCT03068624
Autologous CD8+ SLC45A2-Specific T Lymphocytes With Cyclophosphamide, Aldesleukin, and Ipilimumab in Treating Patients With Metastatic Uveal Melanoma
A Phase 1 study testing Aldesleukin, Autologous CD8+ SLC45A2-specific T Lymphocytes and Cyclophosphamide in people with Metastatic Malignant Neoplasm in the Liver and Metastatic Uveal Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial summary
This phase Ib trial studies the side effects and best dose of autologous CD8 positive (+) SLC45A2-specific T lymphocytes when given together with cyclophosphamide, aldesleukin, and ipilimumab, and to see how well they work in treating patients with uveal melanoma that has spread to other places in the body… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Malignant Neoplasm in the Liver, Metastatic Uveal Melanoma
- What is being tested?
- Aldesleukin, Autologous CD8+ SLC45A2-specific T Lymphocytes and Cyclophosphamide
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Sep 2017to 31 Jul 2025
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- PHERESIS (TURNSTILE 1): Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease or high-risk primary uveal melanoma defined as a recurrence score of > 50% in 5 years. A diagnosis of uveal melanoma can be made clinically without primary tissue evaluation, based on history and records. A prior history of brachytherapy to the eye is sufficient clinical support for a diagnosis of uveal melanoma.
- PHERESIS (TURNSTILE 1): Hematocrit (HCT) >= 24% or hemoglobin (HB) >= 8 g/dL.
- PHERESIS (TURNSTILE 1): Platelets > 50,000.
- PHERESIS (TURNSTILE 1): Expression of human leukocyte antigen (HLA)-A:0201 or HLA-A:2402.
- PHERESIS (TURNSTILE 1): Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of 0-1.
- PHERESIS (TURNSTILE 1): Women of childbearing potential (WOCBP) must be using an adequate method of contraception to avoid pregnancy throughout the study in such a manner that the risk of pregnancy is minimized. Suggested precautions should be used to minimize the risk or pregnancy for at least 1 month before start of therapy, and while women are on study for up to 3 months after completion of the study. WOCBP include any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation or bilateral oophorectomy) or is not postmenopausal.
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- PHERESIS (TURNSTILE 1): Male patients must be willing and able to use an acceptable method of birth control, during and for at least 3 months after completion of the study, if their sexual partners are WOCBP.
- PHERESIS (TURNSTILE 1): Willing and able to give informed consent.
- PHERESIS (TURNSTILE 1): Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible. Certain non-serious exceptions include alopecia, hypothyroidism, neuropathy, nausea, adrenocortical deficiency requiring physiologic replacement dose of steroids, and other conditions noted and approved by the principal investigator (PI).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): ECOG/Zubrod performance status of 0-1 (evaluate at least 1 week before T cell infusion).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Bi-dimensionally measurable disease by palpation on clinical exam, or radiographic imaging per irRC (evaluate at least 1 week before T cell infusion).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): At least 4 weeks must have elapsed since the last chemotherapy, targeted therapy, immunotherapy, radiotherapy, liver-directed therapy, or major surgery. At least 6 weeks for nitrosoureas, mitomycin C and liposomal doxorubicin. If started before T-cell administration, ipilimumab infusions must be least 21 days apart (evaluate at least 1 week before T cell infusion).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): For the ipilimumab cohort only: Toxicity related to prior therapy must either have returned to =< grade 1, baseline, or been deemed irreversible. Certain non-serious exceptions include alopecia, hypothyroidism, neuropathy, nausea, adrenocortical deficiency requiring physiologic replacement dose of steroids, and other conditions noted and approved by the PI (evaluate at least 1 week before T cell infusion).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Patients must have liver metastasis (evaluate at least 1 week before T cell infusion).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Persons of reproductive potential must agree to use and utilize an adequate method of contraception throughout treatment and for at least 3 months after completion of study (evaluate at least 1 week before T cell infusion).
- T CELL INFUSION (INCLUDES CYCLOPHOSPHAMIDE, T CELL, ANTI-CTLA4 INFUSIONS AND SC IL-2) (TURNSTILE 2): Willing and able to give informed consent (evaluate at least 1 week before T cell infusion).
Who cannot join
- PHERESIS: Secondary malignancy is allowed providing it does not require concurrent therapy.
- PHERESIS: Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to pheresis.
- PHERESIS: Significant cardiovascular abnormalities as defined by any one of the following:
- Congestive heart failure
- Clinically significant hypotension
- Symptoms of coronary artery disease (angina, dyspnea)
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- Presence of cardiac arrhythmias on electrocardiogram (EKG) requiring drug therapy
- PHERESIS: Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the investigator to be unacceptable. Acceptable exclusions include: Hashimoto's thyroiditis, type 1 diabetes mellitus, and other localized or inactive conditions with approval of the PI.
- PHERESIS: Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
- PHERESIS: Positive screening tests for human immunodeficiency virus (HIV), hepatitis B virus (Hep B), and hepatitis C virus (Hep C). If positive results are not indicative of true active or chronic infection, the patient can be treated.
- PHERESIS: Participation in any other immunotherapy treatment, that in the opinion of the principal investigator would be unsafe to receive further checkpoint blockade immunotherapy
- White blood cell (WBC) =< 2000/uL (prior to cyclophosphamide and T cell infusions).
- Hct =< 24% or Hb =< 8 g/dL (prior to cyclophosphamide and T cell infusions).
- Absolute neutrophil count (ANC) =< 1000 (prior to cyclophosphamide and T cell infusions).
- Platelets =< 50,000 (prior to cyclophosphamide and T cell infusions).
- Creatinine >= 3.0 x upper limit of normal (ULN) (prior to cyclophosphamide and T cell infusions).
- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) >= 5 x ULN (since all patients will have liver metastasis) (prior to cyclophosphamide and T cell infusions).
- Bilirubin >= 3 x ULN (prior to cyclophosphamide and T cell infusions).
- Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to entry.
- Clinically significant pulmonary dysfunction, as determined by medical history and physical exam. Patients so identified will undergo pulmonary functions testing and those with forced expiratory volume in one second (FEV1) < 2.0 L or diffusing capacity of the lung for carbon monoxide (DLCO) (corrected [corr] for hemoglobin [Hgb]) < 50% will be excluded.
- Steroids (at prednisone equivalent doses > 10 mg) are not permitted 3 days prior to T cell infusion and concurrently during therapy. Exceptions include use of systemic prednisone equivalent doses =< 10 mg/ day, topical steroids or physiologic replacement dose of steroids for adrenocortical deficiency.
- Any non-oncology vaccine therapy used for the prevention of infectious disease within 1 month before or after any ipilimumab dose.
- Patients may not be on any other treatments for their cancer aside from those included in the protocol. Patients may not undergo another form of treatment concurrently with this study. Oncology supportive treatments such as growth factors, bone modifying agents, pain or nausea management are allowed.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase Ib Study of Cellular Adoptive Immunotherapy Using Autologous Cd8+ Antigen-Specific T Cells and Anti-Ctla4 for Patients With Metastatic Uveal Melanoma
This phase Ib trial studies the side effects and best dose of autologous CD8 positive (+) SLC45A2-specific T lymphocytes when given together with cyclophosphamide, aldesleukin, and ipilimumab, and to see how well they work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). To make specialized CD8+ T cells, researchers separate out T cells collected from patients' blood and treat them so they are able to target melanoma cells. The blood cells are then given back to the patients. This is known as "adoptive T cell transfer" or "adoptive T cell therapy." Drugs used in chemotherapy, such as cyclophosphamide, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Biological therapies, such as aldesleukin, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving autologous CD8+ SLC45A2-specific T lymphocytes together with cyclophosphamide, aldesleukin, and ipilimumab may work better in treating patients with metastatic uveal melanoma.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the maximum tolerated dose (MTD) of adoptively transferred SLC45A2-specific cytotoxic T-lymphocytes (CTL) for the treatment of patients with metastatic uveal melanoma.
SECONDARY OBJECTIVES:
- To establish the anti-tumor efficacy as measured by immune-related response criteria (irRC) and duration of response in metastatic uveal melanoma patients receiving autologous CD8+ T cells against SLC45A2.
II. To assess the safety and tolerability of adoptively transferred SLC45A2-specific CTL in combination with immune checkpoint blockade in metastatic uveal melanoma patients.
III. To quantify in vivo numeric and functional persistence of transferred CTL, and development of antigen spreading in metastatic uveal melanoma patients.
IV. To assess overall survival and progression-free survival in metastatic uveal melanoma patients.
OUTLINE: This is a dose escalation study of autologous CD8+ SLC45A2-specific T lymphocytes.
PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 30-60 minutes on day -2.
T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin twice daily (BID) subcutaneously (SC) for 14 days in the absence of disease progression or unacceptable toxicity.
POST T-CELL INFUSION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 84 and 168, and then every 3 months for up to 5 years.
- Being tested
- Aldesleukin, Autologous CD8+ SLC45A2-specific T Lymphocytes, Cyclophosphamide, Ipilimumab
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AldesleukinBiological
Also called 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2
Given SC
Autologous CD8+ SLC45A2-specific T LymphocytesBiological
Also called Autologous SLC45A2-specific CTLs, Autologous SLC45A2-specific Cytotoxic T Lymphocytes
Given via hepatic arterial infusion via central catheter
CyclophosphamideDrug
Also called (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, Ciclofosfamida
Given IV
IpilimumabBiological
Also called Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) | Experimental | PREPARATIVE REGIMEN: Patients receive cyclophosphamide IV over 30-60 minutes on day -2.
T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin BID SC for 14 days in the absence of disease progression or unacceptable toxicity.
POST T-CELL INFUSION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity. Receives: Biological: Aldesleukin; Biological: Autologous CD8+ SLC45A2-specific T Lymphocytes; Drug: Cyclophosphamide; Biological: Ipilimumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum tolerated dose (MTD)
As determined by dose limiting toxicity (DLT). MTD defined at the highest dose at which no more than 1 in 6 patients has experienced DLT.
Measured: Up to 6 weeks
Secondary outcomes (7)
Overall response rate
As measured by immune-related response criteria. Overall response will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. Logistic regression will be used to assess the impact of patient characteristics on the overall response rate.
Measured: Up to 5 years
Duration of clinical response (DOR)
DOR will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the log-rank test. Cox (proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes. Continuous variables (e.g., age, etc.) will be summarized using the mean (standard deviation) or median (range). Frequency tables will be used to summarize categorical variables.
Measured: From the start of study treatment up to 5 years
Persistence of in vivo T cells and non-target antigen recognition
Continuous variables (e.g., age, etc.) will be summarized using the mean (standard deviation) or median (range). Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the log-rank test. Cox proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes.
Measured: From the start of study treatment up to 5 years
Overall survival (OS)
OS will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the log-rank test. Cox (proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes. Continuous variables (e.g., age, etc.) will be summarized using the mean (standard deviation) or median (range). Frequency tables will be used to summarize categorical variables.
Measured: From the start of study treatment up to 5 years
Progression-free survival (PFS)
PFS will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the log-rank test. Cox (proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes. Continuous variables (e.g., age, etc.) will be summarized using the mean (standard deviation) or median (range). Frequency tables will be used to summarize categorical variables.
Measured: From the start of study treatment up to 5 years
Time to response
Continuous variables (e.g., age, etc.) will be summarized using the mean (standard deviation) or median (range). Frequency tables will be used to summarize categorical variables. The distribution of time-to-event endpoints will be estimated using the method of Kaplan and Meier. Comparison of time-to-event endpoints by important subgroups of patients will be made using the log-rank test. Cox proportional hazards) regression will be used to evaluate multivariable predictive models of time-to-event outcomes.
Measured: From the start of study treatment up to 5 years
Incidence of toxicity
Toxicity will be monitored simultaneously using the Bayesian approach of Thall, Simon, Estey and the extension by Thall and Sung. An Efficacy/ Summary will be submitted to the Investigational New Drug (IND) Office Medical Monitor after every six evaluable patients complete 12 weeks of study treatment.
Measured: Up to 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Mar 2017
- Study start8 Sep 2017
- Primary completion31 Dec 2022
- Study completion31 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Malignant Neoplasm in the LiverStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sapna P Patel, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03068624
- Sponsor's protocol ID
- 2016-0414
- Other IDs
- NCI-2018-01291, 2016-0414
- Status last verified
- Jan 2024
- First submitted
- 24 Feb 2017
- Last updated
- 25 Jan 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Study of Cellular Adoptive Immunotherapy Using Autologous Cd8+ Antigen-Specific T Cells and Anti-Ctla4 for Patients With Metastatic Uveal Melanoma
- ClinicalTrials.gov ID
- NCT03068624
- Acronym / sponsor ID
- 2016-0414
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 34 participants (actual)
- Lead sponsor
- M.D. Anderson Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 8 Sep 2017 (actual)
- Primary completion
- 31 Dec 2022 (actual)
- Study completion
- 31 Jul 2025 (estimated)
- First posted
- 3 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase Ib trial studies the side effects and best dose of autologous CD8 positive (+) SLC45A2-specific T lymphocytes when given together with cyclophosphamide, aldesleukin, and ipilimumab, and to see how well they work in treating patients with uveal melanoma that has spread to other places in the body (metastatic). To make specialized CD8+ T cells, researchers separate out T cells collected from patients' blood and treat them so they are able to target melanoma cells. The blood cells are then given back to the patients. This is known as "adoptive T cell transfer" or "adoptive T cell therapy." Drugs used in chemotherapy, such as cyclophosphamide, may work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Biological therapies, such as aldesleukin, use substances made from living organisms that may stimulate the immune system in different ways and stop tumor cells from growing. Immunotherapy with monoclonal antibodies, such as ipilimumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving autologous CD8+ SLC45A2-specific T lymphocytes together with cyclophosphamide, aldesleukin, and ipilimumab may work better in treating patients with metastatic uveal melanoma.
Detailed description
PRIMARY OBJECTIVE:
- To determine the maximum tolerated dose (MTD) of adoptively transferred SLC45A2-specific cytotoxic T-lymphocytes (CTL) for the treatment of patients with metastatic uveal melanoma.
SECONDARY OBJECTIVES:
- To establish the anti-tumor efficacy as measured by immune-related response criteria (irRC) and duration of response in metastatic uveal melanoma patients receiving autologous CD8+ T cells against SLC45A2.
II. To assess the safety and tolerability of adoptively transferred SLC45A2-specific CTL in combination with immune checkpoint blockade in metastatic uveal melanoma patients.
III. To quantify in vivo numeric and functional persistence of transferred CTL, and development of antigen spreading in metastatic uveal melanoma patients.
IV. To assess overall survival and progression-free survival in metastatic uveal melanoma patients.
OUTLINE: This is a dose escalation study of autologous CD8+ SLC45A2-specific T lymphocytes.
PREPARATIVE REGIMEN: Patients receive cyclophosphamide intravenously (IV) over 30-60 minutes on day -2.
T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin twice daily (BID) subcutaneously (SC) for 14 days in the absence of disease progression or unacceptable toxicity.
POST T-CELL INFUSION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up at days 84 and 168, and then every 3 months for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) | Experimental | Biological: Aldesleukin, Biological: Autologous CD8+ SLC45A2-specific T Lymphocytes, Drug: Cyclophosphamide, Biological: IpilimumabPREPARATIVE REGIMEN: Patients receive cyclophosphamide IV over 30-60 minutes on day -2. T-CELL INFUSION: Patients receive autologous CD8+ SLC45A2-specific T lymphocytes via hepatic arterial infusion via central catheter over 60 minutes on day 0. Within 6 hours of T-cell infusion, patients also receive aldesleukin BID SC for 14 days in the absence of disease progression or unacceptable toxicity. POST T-CELL INFUSION: Patients receive ipilimumab IV over 90 minutes on days 1, 22, 43, and 64 in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- PHERESIS (TURNSTILE 1): Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease or high-risk primary uveal melanoma defined as a recurrence score of > 50% in 5 years. A diagnosis of uveal melanoma can be made clinically without primary tissue evaluation, based on history and records. A prior history of brachytherapy to the eye is sufficient clinical support for a diagnosis of uveal melanoma.
- PHERESIS (TURNSTILE 1): Hematocrit (HCT) >= 24% or hemoglobin (HB) >= 8 g/dL.
- PHERESIS (TURNSTILE 1): Platelets > 50,000.
- PHERESIS (TURNSTILE 1): Expression of human leukocyte antigen (HLA)-A:0201 or HLA-A:2402.
- PHERESIS (TURNSTILE 1): Eastern Cooperative Oncology Group (ECOG)/ Zubrod performance status of 0-1.
Key exclusion criteria (23 listed)
- PHERESIS: Secondary malignancy is allowed providing it does not require concurrent therapy.
- PHERESIS: Pregnant women, nursing mothers, men or women of reproductive ability who are unwilling to use effective contraception. Women of childbearing potential with a positive pregnancy test within 3 days prior to pheresis.
- PHERESIS: Significant cardiovascular abnormalities as defined by any one of the following:
- PHERESIS: Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of autoimmune disease (e.g. systemic lupus erythematosus, vasculitis, infiltrating lung disease) whose possible progression during treatment would be considered by the investigator to be unacceptable. Acceptable exclusions include: Hashimoto's thyroiditis, type 1 diabetes mellitus, and other localized or inactive conditions with approval of the PI.
- PHERESIS: Any underlying medical or psychiatric condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AldesleukinAlso: 125-L-Serine-2-133-interleukin 2, Proleukin, r-serHuIL-2, Recombinant Human IL-2Given SC | Biological | Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) |
| Autologous CD8+ SLC45A2-specific T LymphocytesAlso: Autologous SLC45A2-specific CTLs, Autologous SLC45A2-specific Cytotoxic T LymphocytesGiven via hepatic arterial infusion via central catheter | Biological | Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) |
| CyclophosphamideAlso: (-)-Cyclophosphamide, 2H-1,3,2-Oxazaphosphorine, 2-[bis(2-chloroethyl)amino]tetrahydro-, 2-oxide, monohydrate, Carloxan, CiclofosfamidaGiven IV | Drug | Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) |
| IpilimumabAlso: Anti-Cytotoxic T-Lymphocyte-Associated Antigen-4 Monoclonal Antibody, BMS-734016, MDX-010, MDX-CTLA4Given IV | Biological | Treatment (cyclophosphamide, T-cells, aldesleukin, ipilimumab) |
Primary outcome
Maximum tolerated dose (MTD)
Time frame: Up to 6 weeks
As determined by dose limiting toxicity (DLT). MTD defined at the highest dose at which no more than 1 in 6 patients has experienced DLT.
7 secondary outcomes
Overall response rate
Time frame: Up to 5 years
Duration of clinical response (DOR)
Time frame: From the start of study treatment up to 5 years
Persistence of in vivo T cells and non-target antigen recognition
Time frame: From the start of study treatment up to 5 years
Overall survival (OS)
Time frame: From the start of study treatment up to 5 years
Progression-free survival (PFS)
Time frame: From the start of study treatment up to 5 years
Time to response
Time frame: From the start of study treatment up to 5 years
Incidence of toxicity
Time frame: Up to 5 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jan 2024.
- MD Anderson Cancer CenterLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sapna P Patel principal investigator
M.D. Anderson Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Aldesleukin, Autologous CD8+ SLC45A2-specific T Lymphocytes and Cyclophosphamide in people with Metastatic Malignant Neoplasm in the Liver and Metastatic Uveal Melanoma, run by M.D. Anderson Cancer Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 16 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jan 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum tolerated dose (MTD) (time frame: Up to 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jan 2024.