Metastatic MelanomaPhase 2F5NCT00910650
Study of Gene Modified Immune Cells in Patients With Advanced Melanoma
A Phase 2 study testing F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells and non-myeloablative conditioning chemotherapy in people with Metastatic Melanoma, run by Jonsson Comprehensive Cancer Center at 1 site in United States.
Trial summary
The purpose of this phase 2 study is to find the best way to give this new experimental regimen and determine if it can treat metastatic melanoma in humans. In this phase 2 study, the experimental products are given initially to a group of 8 people. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells and non-myeloablative conditioning chemotherapy
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Oct 2009to 30 May 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- Histologically confirmed melanoma that is considered surgically incurable with either:
- Stage IIIc melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis.
- Stage IV melanoma (M1a, M1b or M1c). At least 1 lesion amenable for outpatient biopsies; this should be a cutaneous or palpable metastatic site or a deeper site accessible by image-guided biopsy that is deemed safe to access by the treating physicians and interventional radiologists. Patients without accessible lesions for biopsy but with prior tissue available from metastatic disease would be eligible at the investigator's discretion.
- MART-1 positive melanoma by RT-PCR or Immuno-histochemical (IHC).
- HLA-A*0201 (HLA-A2.1) positivity by molecular subtyping*.
- Age greater than or equal to 18 years old.
Show all 23Show fewer
- Life expectancy greater than 3 months assessed by a study physician.
- A minimum of one measurable lesion defined as:
- Meeting the criteria for measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST).
- Skin lesion(s) selected as non-completely biopsied target lesion(s) that can be accurately measured and recorded by color photography with a ruler to document the size of the target lesion(s).
- No restriction based on prior treatments.
- Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 or 1.
- Adequate bone marrow and hepatic function determined within 30-60 days prior to enrollment, defined as:
- Absolute neutrophil count >= 1.5 x 109 cells/L.
- Platelets >= 100 x 109/L.
- Hemoglobin >= 10 g/dL.
- Aspartate and alanine aminotransferases (AST, ALT) =< 2.5 x ULN (=< 5 x ULN, if documented liver metastases are present).
- Total bilirubin =< 2 x Upper Limit of Normal (ULN) (except patients with documented Gilbert's syndrome).
- Creatinine < 2 mg/dl (or a glomerular filtration rate > 60).
- Must be willing and able to accept at least two leukapheresis procedures.
- Must be willing and able to accept at least two tumor biopsies.
- Must be willing and able to provide written informed consent.
- Patients with HLA-A*0205 (HLA-A2.5) positivity by molecular subtyping may be eligible if there is demonstration that they can correctly present the MART-126-35 epitope as stimulators for IFN-gamma production by MART-1 F5 TCR transgenic cells.
Who cannot join
- Previously known hypersensitivity to any of the agents used in this study.
- Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol. However, cell harvesting by leukapheresis may be performed before one month from prior therapy if the study investigators consider that it will not have a detrimental impact on the generation of the two cell therapies in this protocol.
- History of, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.). Patients will be eligible if prior autoimmune disease is not deemed to be active (e.g. fibrotic damage of the thyroid after thyroiditis or its treatment, with stable thyroid hormone replacement therapy). Vitiligo will not be a basis for exclusion.
- History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin.
- Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed).
- HIV seropositivity or other congenital or acquired immune deficiency state, which would increase the risk of opportunistic infections and other complications during chemotherapy-induced lymphodepletion. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist.
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- Hepatitis B or C seropositivity with evidence of ongoing liver damage, which would increase the likelihood of hepatic toxicities from the chemotherapy conditioning regimen and supportive treatments. If there is a positive result in the infectious disease testing that was not previously known, the patient will be referred to their primary physician and/or infectious disease specialist.
- Dementia or significantly altered mental status that would prohibit the understanding or rendering of informed consent and compliance with the requirements of this protocol.
- Clinically active brain metastases. Radiological documentation of absence of active brain metastases at screening is required for all patients. Prior evidence of brain metastasis successfully treated with surgery or radiation therapy will not be exclusion for participation as long as they are deemed under control at the time of study enrollment.
- Pregnancy or breast-feeding. Female patients must be surgically sterile or be postmenopausal for two years, or must agree to use effective contraception during the period of treatment and 6 months after. All female patients with reproductive potential must have a negative pregnancy test (serum/urine) within 14 days from starting the conditioning chemotherapy. The definition of effective contraception will be based on the judgment of the study investigators.
- Since IL-2 is administered following cell infusion:
- Patients will be excluded if they have a history of clinically significant ECG abnormalities, symptoms of cardiac ischemia or arrhythmias and have a left ventricular ejection fraction (LVEF) < 45% on a cardiac stress test (stress thallium, stress MUGA, dobutamine echocardiogram, or other stress test).
- Similarly, patients who are 50 years old with a baseline LVEF < 45% will be excluded.
- Patients with ECG results of any conduction delays (PR interval >200ms, QTC > 480ms), sinus bradycardia (resting heart rate <50 beats per minute), sinus tachycardia (HR>120 beats per minute) will be evaluated by a cardiologist prior to starting the trial. Patients with any arrhythmias, including atrial fibrillation/atrial flutter, excessive ectopy (defined as >20 PVCs per minute), ventricular tachycardia, 3rd degree heart block will be excluded from the study unless cleared by a cardiologist.
- Patients with pulmonary function test abnormalities as evidenced by a forced expiratory volume at one second/forced vital capacity (FEV1/FVC)< 70% of predicted for normality will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of California Los Angeles, David Geffen School of Medicine
Los Angeles, California, 90095
About this study
Official title: Adoptive Transfer of MART-1 F5 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) After a Nonmyeloablative Conditioning Regimen, With Administration of MART-126•35-Pulsed Dendritic Cells and Interleukin-2, in Patients With Advanced Melanoma
The purpose of this phase 2 study is to find the best way to give this new experimental regimen and determine if it can treat metastatic melanoma in humans. In this phase 2 study, the experimental products are given initially to a group of 8 people. If safe and found to have significant anti-tumor activity, it will be given to up to 14 other people, for a total of 22 people in this study. Physicians watch subjects carefully for any harmful side effects. Although the experimental regimen has been well tested in laboratory and animal studies, and a similar regimen has been given to a group of patients at the National Cancer Institute in Bethesda, MD, the side effects in people cannot be completely known ahead of time. This protocol is offered only to people whose condition cannot be helped by other known treatments.
The study procedures will start with the collection of white blood cells through apheresis (a procedure in which blood is drawn from a patient and separated into its components, some of which are retained, such as white blood cells, and the remainder returned by transfusion to the patient).
Read more
Subjects will be asked to undergo two aphereses, one to make the gene-modified MART-1 TCR CTLs (cytolytic T lymphocyte) and the dendritic cell vaccines, and a second one after the subject receives the gene modified cells to later study them in the blood.
On the day of the first apheresis, subjects will be admitted to the hospital and will receive chemotherapy over the next five days which decreases the risk of rejection of the transferred cells by the subject's immune system and facilitates their expansion and attack of the melanoma lesions. During this time, the gene-modified MART-1 TCR CTLs and the dendritic cells will be manufactured in the laboratory from the apheresis product and will be extensively tested to assure that they express the appropriate TCR and that they do not contain any contaminating bacteria or virus. Then the gene-modified MART-1 TCR CTLs will be given back to the subject through a vein in the arm. It will be followed by vaccination with the dendritic cells under the skin. During the next fourteen days, subjects will also receive interleukin 2 (IL-2), which is a standard treatment for patients with metastatic melanoma. During the next 2 to 3 weeks, subjects will stay in the hospital until the study investigators determine that the subject has fully recovered from all of the procedures, and it is safe for the subject to go home. Chemotherapy frequently causes a decrease in the platelet or red blood cells, and therefore subjects may require platelet and/or red blood cell transfusions.
Read the detailed description
This is a two-stage phase II clinical trial with the combined primary endpoints to determine the safety, feasibility and anti-tumor activity of adoptive transfer of peripheral blood mononuclear cells (PBMC) genetically engineered to express the alpha and beta chains of a high affinity T cell receptor (TCR) specific for the HLA-A*0201-restricted MART-1 melanoma tumor antigen to patients with locally advanced or metastatic melanoma. This gene transfer will be facilitated by a retroviral vector pseudotyped with a gibbon ape leukemia virus (GaLV) envelope. The two transgenes are linked by a picornavirus 2A sequence. Their expression is driven by the retroviral long terminal repeat (LTR).
Patients with MART-1-positive locally advanced or metastatic melanoma who are HLA-A*0201-positive, and HIV, hepatitis B and C seronegative, will receive a non-myeloablative but lymphocyte depleting chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine, and then receive the adoptive transfer of autologous PBMC transduced with the MSGV1-F5AfT2AB retroviral vector, which expresses a high affinity TCR for the MART-1 melanoma antigen (MART-1 F5 TCR). The cell dose will be up to 10^9 autologous PBMC transduced with the MSGV1-F5AfT2AB retroviral vector. The transgenic T cells will be infused fresh on the day of harvest as done in the last three patients within this protocol, prior to which, thawed cryopreserved cells were infused. Following adoptive cell transfer, patients will receive MART-1.26-35 peptide-pulsed dendritic cell (DC) vaccines and low dose interleukin-2 (IL-2).
The MART-1 F5 TCR was provided by Dr. Stephen A. Rosenberg from the Surgery Branch, National Cancer Institute (NCI). The MART-1 F5 TCR is derived from the DMF5 tumor infiltrating lymphocyte (TIL) clone, and was selected from several MART-1-specific TCRs because of its high affinity and biological activity. This TCR delivered by the same retroviral vector is currently in clinical testing at the Surgery Branch/NCI. Both the NCI clinical trial and the trial at University of California at Los Angeles (UCLA) are based on the same retrovirus expressing the MART-1 F5 TCR used to transduce whole PBMC and re-infused to patients after a non-myeloablative but lymphodepleting chemotherapy conditioning regimen. Major differences between both clinical trials include the shorter ex vivo expansion of TCR transduced PBMC, the use of MART-126-35 peptide pulsed DC and the use of positron imaging tomography (PET) for non-invasive imaging of adoptively transferred TCR transgenic cells in the UCLA clinical trial.
The primary endpoints will be safety, feasibility and objective tumor response. The phase II clinical trial design will have two treatment stages following a Simon optimal two-stage clinical phase II clinical trial design 1. The clinical trial will have an initial stage with 8 patients followed by a second stage with up to 22 patients.
Safety will be determined in stage one, and if 3 out of 8 patients have MART-1 F5 TCR-induced dose limiting toxicities (DLT), then further accrual will not be warranted. Feasibility will be also determined in the first stage, and if 3 out of 8 patients cannot receive the intended cellular therapies, or if they result in suboptimal TCR transgenic cell in vivo persistence, further accrual will not be warranted to the protocol as currently designed. Objective tumor responses will be determined by RECIST objective response criteria with a design to rule out a 10% response rate as the null hypothesis, and a 35% response rate as the alternative hypothesis. With this statistical design, if 2 or more of 8 patients in stage one have an objective response, the study will proceed to stage two and accrue a total of 22 patients. If 5 or more patients in the overall study have a complete response (CR) or partial response (PR), which combined result in the objective response rate, the study will be declared positive.
Secondary study endpoints are transgenic T cell persistence in humans and their ability to home to MART-1 positive melanoma metastasis. Analysis will be performed by sampling of peripheral blood and tumor deposits for T cell persistence and by non-invasive metabolic imaging using PET scans.
- Conditions
- Metastatic Melanoma
- Being tested
- F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells, non-myeloablative conditioning chemotherapy
- Keywords
- Adoptive transfer therapy, Dendritic cell vaccines
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cellsBiological
Also called F5 TCR transgenic cells, MART-1 peptide pulsed dendritic cells, Interleukin-2 (aldesleukin)
After chemotherapy, patients receive up to 1 x 10(9) MART-1 F5 TCR transgenic T cells infused i.v., 1 x 10(7) MART-1 peptide pulsed dendritic cells intradermally, and low dose IL-2 500,000 IU/m2 s.c. twice daily for 14 days.
non-myeloablative conditioning chemotherapyDrug
Patients receive non-myeloablative conditioning chemotherapy with Cyclophosphamide 60 mg/kg/day x 2 days and Fludarabine 25 mg/m2/day i.v. over 30 minutes for 4 days
| Study group | Role | What they receive |
|---|---|---|
| F5 TCR transgenic cells | Experimental | F5 TCR transgenic cell adoptive transfer therapy Receives: Biological: F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells; Drug: non-myeloablative conditioning chemotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Response Rate: The Number of Participants Who Completed the Maximum Time Allowed on Study Without Being Affected by Tumor Recurrence or Progression.
Measured: every 90 days for up to 3 years
Secondary outcomes (1)
Overall Survival (OS)
Overall survival is measured until the patient passes away
Measured: Baseline from treatment for the life of the participant > 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2009 (estimated)
- Study start13 Oct 2009
- Primary completion30 May 2019
- Study completion30 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Jonsson Comprehensive 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jonsson Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- California Institute of Technology, University of Southern California, University of Connecticut, National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Antoni Ribas, MD, Principal investigator, University of California, Los AngelesBartosz Chmielowski, MD, PhD, Principal investigator, University of California, Los AngelesJames S Economou, MD, PhD, Principal investigator, University of California, Los AngelesJohn A Glaspy, MD, MPH, Principal investigator, University of California, Los Angeles
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00910650
- Sponsor's protocol ID
- 10-001212
- Other IDs
- 08-02-020
- Acronym
- F5
- Status last verified
- Feb 2020
- First submitted
- 1 May 2009
- Last updated
- 6 Dec 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Mehta A, Kim YJ, Robert L, Tsoi J, Comin-Anduix B, Berent-Maoz B, Cochran AJ, Economou JS, Tumeh PC, Puig-Saus C, Ribas A. Immunotherapy Resistance by Inflammation-Induced Dedifferentiation. Cancer Discov. 2018 Aug;8(8):935-943. doi: 10.1158/2159-8290.CD-17-1178. Epub 2018 Jun 13.
PubMed 29899062Nowicki TS, Escuin-Ordinas H, Avramis E, Chmielowski B, Chodon T, Berent-Maoz B, Wang X, Kaplan-Lefko P, Yang L, Baltimore D, Economou JS, Ribas A, Comin-Anduix B. Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products. J Immunother. 2018 Jun;41(5):248-259. doi: 10.1097/CJI.0000000000000216.
PubMed 29470191Ma C, Cheung AF, Chodon T, Koya RC, Wu Z, Ng C, Avramis E, Cochran AJ, Witte ON, Baltimore D, Chmielowski B, Economou JS, Comin-Anduix B, Ribas A, Heath JR. Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy. Cancer Discov. 2013 Apr;3(4):418-29. doi: 10.1158/2159-8290.CD-12-0383. Epub 2013 Mar 21.
PubMed 23519018
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adoptive Transfer of MART-1 F5 TCR Engineered Peripheral Blood Mononuclear Cells (PBMC) After a Nonmyeloablative Conditioning Regimen, With Administration of MART-126•35-Pulsed Dendritic Cells and Interleukin-2, in Patients With Advanced Melanoma
- ClinicalTrials.gov ID
- NCT00910650
- Acronym / sponsor ID
- F5 / 10-001212
- Conditions
- Metastatic Melanoma
- Keywords
- Adoptive transfer therapy, Dendritic cell vaccines
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Jonsson Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- California Institute of Technology, University of Southern California, University of Connecticut, National Cancer Institute (NCI)
- Study start
- 13 Oct 2009 (actual)
- Primary completion
- 30 May 2019 (actual)
- Study completion
- 30 May 2019 (actual)
- First posted
- 1 Jun 2009 (estimated)
- Results
- Posted 4 Aug 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this phase 2 study is to find the best way to give this new experimental regimen and determine if it can treat metastatic melanoma in humans. In this phase 2 study, the experimental products are given initially to a group of 8 people. If safe and found to have significant anti-tumor activity, it will be given to up to 14 other people, for a total of 22 people in this study. Physicians watch subjects carefully for any harmful side effects. Although the experimental regimen has been well tested in laboratory and animal studies, and a similar regimen has been given to a group of patients at the National Cancer Institute in Bethesda, MD, the side effects in people cannot be completely known ahead of time. This protocol is offered only to people whose condition cannot be helped by other known treatments.
The study procedures will start with the collection of white blood cells through apheresis (a procedure in which blood is drawn from a patient and separated into its components, some of which are retained, such as white blood cells, and the remainder returned by transfusion to the patient).
Subjects will be asked to undergo two aphereses, one to make the gene-modified MART-1 TCR CTLs (cytolytic T lymphocyte) and the dendritic cell vaccines, and a second one after the subject receives the gene modified cells to later study them in the blood.
On the day of the first apheresis, subjects will be admitted to the hospital and will receive chemotherapy over the next five days which decreases the risk of rejection of the transferred cells by the subject's immune system and facilitates their expansion and attack of the melanoma lesions. During this time, the gene-modified MART-1 TCR CTLs and the dendritic cells will be manufactured in the laboratory from the apheresis product and will be extensively tested to assure that they express the appropriate TCR and that they do not contain any contaminating bacteria or virus. Then the gene-modified MART-1 TCR CTLs will be given back to the subject through a vein in the arm. It will be followed by vaccination with the dendritic cells under the skin. During the next fourteen days, subjects will also receive interleukin 2 (IL-2), which is a standard treatment for patients with metastatic melanoma. During the next 2 to 3 weeks, subjects will stay in the hospital until the study investigators determine that the subject has fully recovered from all of the procedures, and it is safe for the subject to go home. Chemotherapy frequently causes a decrease in the platelet or red blood cells, and therefore subjects may require platelet and/or red blood cell transfusions.
Detailed description
This is a two-stage phase II clinical trial with the combined primary endpoints to determine the safety, feasibility and anti-tumor activity of adoptive transfer of peripheral blood mononuclear cells (PBMC) genetically engineered to express the alpha and beta chains of a high affinity T cell receptor (TCR) specific for the HLA-A*0201-restricted MART-1 melanoma tumor antigen to patients with locally advanced or metastatic melanoma. This gene transfer will be facilitated by a retroviral vector pseudotyped with a gibbon ape leukemia virus (GaLV) envelope. The two transgenes are linked by a picornavirus 2A sequence. Their expression is driven by the retroviral long terminal repeat (LTR).
Patients with MART-1-positive locally advanced or metastatic melanoma who are HLA-A*0201-positive, and HIV, hepatitis B and C seronegative, will receive a non-myeloablative but lymphocyte depleting chemotherapy conditioning regimen consisting of cyclophosphamide and fludarabine, and then receive the adoptive transfer of autologous PBMC transduced with the MSGV1-F5AfT2AB retroviral vector, which expresses a high affinity TCR for the MART-1 melanoma antigen (MART-1 F5 TCR). The cell dose will be up to 10^9 autologous PBMC transduced with the MSGV1-F5AfT2AB retroviral vector. The transgenic T cells will be infused fresh on the day of harvest as done in the last three patients within this protocol, prior to which, thawed cryopreserved cells were infused. Following adoptive cell transfer, patients will receive MART-1.26-35 peptide-pulsed dendritic cell (DC) vaccines and low dose interleukin-2 (IL-2).
The MART-1 F5 TCR was provided by Dr. Stephen A. Rosenberg from the Surgery Branch, National Cancer Institute (NCI). The MART-1 F5 TCR is derived from the DMF5 tumor infiltrating lymphocyte (TIL) clone, and was selected from several MART-1-specific TCRs because of its high affinity and biological activity. This TCR delivered by the same retroviral vector is currently in clinical testing at the Surgery Branch/NCI. Both the NCI clinical trial and the trial at University of California at Los Angeles (UCLA) are based on the same retrovirus expressing the MART-1 F5 TCR used to transduce whole PBMC and re-infused to patients after a non-myeloablative but lymphodepleting chemotherapy conditioning regimen. Major differences between both clinical trials include the shorter ex vivo expansion of TCR transduced PBMC, the use of MART-126-35 peptide pulsed DC and the use of positron imaging tomography (PET) for non-invasive imaging of adoptively transferred TCR transgenic cells in the UCLA clinical trial.
The primary endpoints will be safety, feasibility and objective tumor response. The phase II clinical trial design will have two treatment stages following a Simon optimal two-stage clinical phase II clinical trial design 1. The clinical trial will have an initial stage with 8 patients followed by a second stage with up to 22 patients.
Safety will be determined in stage one, and if 3 out of 8 patients have MART-1 F5 TCR-induced dose limiting toxicities (DLT), then further accrual will not be warranted. Feasibility will be also determined in the first stage, and if 3 out of 8 patients cannot receive the intended cellular therapies, or if they result in suboptimal TCR transgenic cell in vivo persistence, further accrual will not be warranted to the protocol as currently designed. Objective tumor responses will be determined by RECIST objective response criteria with a design to rule out a 10% response rate as the null hypothesis, and a 35% response rate as the alternative hypothesis. With this statistical design, if 2 or more of 8 patients in stage one have an objective response, the study will proceed to stage two and accrue a total of 22 patients. If 5 or more patients in the overall study have a complete response (CR) or partial response (PR), which combined result in the objective response rate, the study will be declared positive.
Secondary study endpoints are transgenic T cell persistence in humans and their ability to home to MART-1 positive melanoma metastasis. Analysis will be performed by sampling of peripheral blood and tumor deposits for T cell persistence and by non-invasive metabolic imaging using PET scans.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| F5 TCR transgenic cells | Experimental | Biological: F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells, Drug: non-myeloablative conditioning chemotherapyF5 TCR transgenic cell adoptive transfer therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (23 listed)
- Histologically confirmed melanoma that is considered surgically incurable with either:
- MART-1 positive melanoma by RT-PCR or Immuno-histochemical (IHC).
- HLA-A*0201 (HLA-A2.1) positivity by molecular subtyping*.
- Age greater than or equal to 18 years old.
- Life expectancy greater than 3 months assessed by a study physician.
Key exclusion criteria (15 listed)
- Previously known hypersensitivity to any of the agents used in this study.
- Received systemic treatment for cancer, including immunotherapy, within one month prior to initiation of dosing within this protocol. However, cell harvesting by leukapheresis may be performed before one month from prior therapy if the study investigators consider that it will not have a detrimental impact on the generation of the two cell therapies in this protocol.
- History of, or significant evidence of risk for, chronic inflammatory or autoimmune disease (eg, Addison's disease, multiple sclerosis, Graves disease, Hashimoto's thyroiditis, inflammatory bowel disease, psoriasis, rheumatoid arthritis, systemic lupus erythematosus, hypophysitis, pituitary disorders, etc.). Patients will be eligible if prior autoimmune disease is not deemed to be active (e.g. fibrotic damage of the thyroid after thyroiditis or its treatment, with stable thyroid hormone replacement therapy). Vitiligo will not be a basis for exclusion.
- History of inflammatory bowel disease, celiac disease, or other chronic gastrointestinal conditions associated with diarrhea or bleeding, or current acute colitis of any origin.
- Potential requirement for systemic corticosteroids or concurrent immunosuppressive drugs based on prior history or received systemic steroids within the last 4 weeks prior to enrollment (inhaled or topical steroids at standard doses are allowed).
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 |
|---|---|---|
| F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cellsAlso: F5 TCR transgenic cells, MART-1 peptide pulsed dendritic cells, Interleukin-2 (aldesleukin)After chemotherapy, patients receive up to 1 x 10(9) MART-1 F5 TCR transgenic T cells infused i.v., 1 x 10(7) MART-1 peptide pulsed dendritic cells intradermally, and low dose IL-2 500,000 IU/m2 s.c. twice daily for 14 days. | Biological | F5 TCR transgenic cells |
| non-myeloablative conditioning chemotherapyPatients receive non-myeloablative conditioning chemotherapy with Cyclophosphamide 60 mg/kg/day x 2 days and Fludarabine 25 mg/m2/day i.v. over 30 minutes for 4 days | Drug | F5 TCR transgenic cells |
Primary outcome
Response Rate: The Number of Participants Who Completed the Maximum Time Allowed on Study Without Being Affected by Tumor Recurrence or Progression.
Time frame: every 90 days for up to 3 years
1 secondary outcome
Overall Survival (OS)
Time frame: Baseline from treatment for the life of the participant > 7 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 29899062Mehta A, Kim YJ, Robert L, Tsoi J, Comin-Anduix B, Berent-Maoz B, Cochran AJ, Economou JS, Tumeh PC, Puig-Saus C, Ribas A. Immunotherapy Resistance by Inflammation-Induced Dedifferentiation. Cancer Discov. 2018 Aug;8(8):935-943. doi: 10.1158/2159-8290.CD-17-1178. Epub 2018 Jun 13.
- Derived from this study: PubMed 29470191Nowicki TS, Escuin-Ordinas H, Avramis E, Chmielowski B, Chodon T, Berent-Maoz B, Wang X, Kaplan-Lefko P, Yang L, Baltimore D, Economou JS, Ribas A, Comin-Anduix B. Characterization of Postinfusion Phenotypic Differences in Fresh Versus Cryopreserved TCR Engineered Adoptive Cell Therapy Products. J Immunother. 2018 Jun;41(5):248-259. doi: 10.1097/CJI.0000000000000216.
- Derived from this study: PubMed 23519018Ma C, Cheung AF, Chodon T, Koya RC, Wu Z, Ng C, Avramis E, Cochran AJ, Witte ON, Baltimore D, Chmielowski B, Economou JS, Comin-Anduix B, Ribas A, Heath JR. Multifunctional T-cell analyses to study response and progression in adoptive cell transfer immunotherapy. Cancer Discov. 2013 Apr;3(4):418-29. doi: 10.1158/2159-8290.CD-12-0383. Epub 2013 Mar 21.
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SI-B036-ST-101 in Advanced/Metastatic Solid Tumors
Locally Advanced /Metastatic Solid Tumors, Locally Advanced / Metastatic Solid Tumors
RecruitingPhase 2
BiCaZO: A Study Combining Two Immunotherapies (Cabozantinib and Nivolumab) to Treat Patients With Advanced Melanoma or Squamous Cell Head and Neck Cancer, an immunoMATCH Pilot Study
Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage III HPV-Mediated (p16-Positive) Oropharyngeal Carcinoma AJCC v8
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.
Antoni Ribas, MD principal investigator
University of California, Los Angeles
Bartosz Chmielowski, MD, PhD principal investigator
University of California, Los Angeles
James S Economou, MD, PhD principal investigator
University of California, Los Angeles
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing F5 TCR transgenic cells and MART-1 peptide pulsed dendritic cells and non-myeloablative conditioning chemotherapy in people with Metastatic Melanoma, run by Jonsson Comprehensive 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 23 inclusion and 15 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: finished, as of the sponsor's last update on 6 Dec 2021. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Aug 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Response Rate: The Number of Participants Who Completed the Maximum Time Allowed on Study Without Being Affected by Tumor Recurrence or Progression. (time frame: every 90 days for up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00910650, which also lists 3 linked publications.
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 6 Dec 2021; AzTrials last refreshed its copy on 6 Nov 2026.