Phase II Study in Patients With Metastatic Ocular Melanoma Using a Non-Myeloablative Lymphocyte Depleting Regimen of Chemotherapy Followed by Infusion of Autologous Tumor-Infiltrating Lymphocytes With or Without High Dose Aldesleukin
- Metastatic ocular melanoma (OM) carries a poor prognosis with estimated survival of 4-6
months. There are no known effective systemic therapies. Metastatic OM is classified as
an orphan disease and there are currently few clinical trial options for these
patients. Thus, novel systemic approaches are desperately needed.
- Administration of autologous tumor infiltrating lymphocytes (TIL) generated from
resected metastatic cutaneous melanoma can induce objective long-term tumor responses.
- Minimally invasive, safe, and effective surgical approaches have been developed in the
Surgery Branch to procure liver tumor tissue for TIL generation.
- To determine whether autologous Young TIL infused with or without the administration of
high-dose aldesleukin may result in clinical tumor regression in patients with
metastatic ocular melanoma receiving a non-myeloablative lymphoid depleting preparative
- To study immunologic correlates associated with Young TIL therapy for ocular melanoma.
- To determine the toxicity of this treatment regimen.
- Patients with metastatic ocular melanoma who are greater than or equal to 18 years of
age, and are physically able to tolerate non-myeloablative chemotherapy. Patients who
can tolerate high-dose aldesleukin will receive it following cell infusion; those who
cannot tolerate high-dose aldesleukin due to medical comorbidities or refuse high-dose
aldesleukin will receive cell infusion without aldesleukin.
- There is no requirement for prior systemic therapies, given the lack of known effective
systemic treatments for metastatic OM.
- Patients will undergo biopsy or resection to obtain tumor for generation of autologous
TIL cultures and autologous cancer cell lines.
- All patients will receive a non-myeloablative lymphocyte depleting preparative regimen
of cyclophosphamide (60 mg/kg/day IV) on days -7 and -6 and fludarabine (25 mg/m2/day
IV) on days -5 through -1.
- On day 0 patients will receive between 1x109 to 2x1011 young TIL and then begin high
dose aldesleukin (720,000 IU/kg IV every 8 hours for up to 15 doses) or no aldesleukin
if they are not medically eligible to receive it.
- A complete evaluation of evaluable lesions will be conducted 4-6 weeks after the last
dose of aldesleukin in the aldesleukin arm and 4-6 weeks after the cell administration
in the no aldesleukin arm.
- Patients will be enrolled into two cohorts. The cohort receiving high-dose aldesleukin
3 (cohort A) will be conducted using a small optimal two-stage Phase II design,
initially 19 patients will be enrolled, and if 4 or more of the first 19 patients have
a clinical response (PR or CR), accrual will continue to 33 patients, targeting a 35%
goal for objective response. For the cohort that will not receive aldesleukin (cohort
B), the study will be conducted as a Minimax two-stage phase II trial. Initially 12
evaluable patients will be enrolled to this cohort, and if 1 or more the first 12 have
a response, then accrual would continue until a total of 21 patients, targeting a 20%
goal for objective response.
Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
To determine whether autologous Young TIL infused + or - the admin of high-dose IL-2 may result in clinical tumor regression in patients with metastatic ocular melanoma receiving a non-myeloablative lymphoid depleting preparative regimen.
Udai S Kammula, M.D.
National Cancer Institute (NCI)
United States: Federal Government
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Bethesda, Maryland 20892|