Phase II Study of Metastatic Melanoma Using a Nonmyeloablative Lymphodepleting Regimen Followed by Melanoma-Reactive T-Cells Sensitized in Vitro With Peptide-Pulsed Drosophila Cells
- Adoptive transfer studies in patients with metastatic melanoma following
lymphodepletion have resulted in up to 50% objective response rates with a 10-15% rate
of complete responses.
- A novel method involves the use of insect cell lines which do not express any native
major histocompatibility complex (MHC) molecules.
- When stably transfected with human MHC molecules and appropriate adhesion and
costimulatory molecules, a Drosophila cell line can potently stimulate tumor-reactivity
in vitro from human peripheral blood lymphocytes (PBL).
- The current proposed transfer of Drosophila-cell stimulated autologous cluster of
differentiation 8 (CD8) plus PBL administered in conjunction with a lymphodepleting
preparative regimen, with or without low-dose aldesleukin would represent a
significantly novel approach to adoptive immunotherapy.
- To determine whether infusion of CD8+ autologous PBL sensitized in vitro with peptide
pulsed HLA-A2-expressing Drosophila cells (CTL-05) and administered in combination with
a lymphodepleting preparative regimen and supportive systemic aldesleukin can result in
clinical tumor regression in human leukocyte antigen serotype within HLA-A A serotype
group (HLA-A2+) patients with metastatic melanoma.
- To determine the safety of the above regimen.
- To investigate the contribution of low-dose systemic aldesleukin to cell efficacy.
Patients who are HLA-A*0201 positive and 18 years of age or older must have
- metastatic melanoma with measurable disease
- been previously treated with aldesleukin for melanoma;
- normal basic laboratory values.
Patients may not have:
- concurrent major medical illnesses;
- any form of primary or secondary immunodeficiency;
- requirement for systemic steroid therapy
- The first 20 patients enrolled (cohort 0) will receive a non-myeloablative lymphocyte
depleting preparative regimen followed by administration of intravenous CTL-05 and
low-dose subcutaneous aldesleukin (daily for 5 days).
- If 3 or more of the 20 patients respond, subsequent patients will be randomized between
two cohorts. Patients in cohort 1 will receive a non-myeloablative lymphocyte depleting
preparative regimen followed by administration of CTL-05 and low-dose subcutaneous
aldesleukin (daily for 5 days). Patients in Cohort 2 will receive a non-myeloablative
lymphocyte depleting preparative regimen followed by administration of CTL-05 and NO
- A complete evaluation will be conducted 8 weeks (plus or minus 2 weeks) after the
initiation of chemotherapy. The trial will be conducted using a small Simon MinMax
Phase II design in the initial phase and a Simon optimal design in the second phase. A
maximum of 35 patients may be accrued to each of cohorts 1 and 2. If no responses are
seen in the first 13 patients receiving no systemic aldesleukin, then accrual to that
cohort will cease. Total enrollment may be up to 90 patients.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Clinical response is assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Complete response (CR) is a disappearance of all target lesions. Partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD. Progression disease (PD) is at least a 20 % increase in the sum of the LD of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more lesions. Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as references the smallest sum LD.
Udo Rudloff, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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