Metastatic Cutaneous Melanoma Clinical Trial
Official title:
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
Background:
- Recent cancer treatment studies have shown that altering a cancer patient's own white
blood cells may help the immune system fight the cancer. In all of these studies,
participants donate their own white blood cells through a procedure called
leukapheresis, and the cells are altered in the laboratory and given back to the
participants. After the cells are given, the patients receive aldesleukin (IL-2) to
help the tumor fighting cells stay alive longer. For individuals with metastatic
melanoma, pieces of melanoma proteins may be added to the collected white blood cells
to help the immune system recognize and attack the cancer cells.
- Researchers are interested in testing a new process in which cells from fruit flies
(Drosophila) are used to help the melanoma proteins attach to the white blood cells.
The fruit fly cells die off shortly after the proteins are introduced to the white
blood cells. Researchers are also interested in determining whether IL-2 treatment is
necessary after this new cancer treatment process.
Objectives:
- To test the safety and effectiveness of modified white blood cells
(Drosophila-generated CTL) as a treatment for metastatic melanoma that has not
responded to standard treatments.
- To determine whether IL-2 treatment improves the effectiveness of Drosophila-generated
cytolytic T lymphocytes (CTL).
Eligibility:
- Individuals at least 18 years of age who have been diagnosed with metastatic melanoma that
has not responded to previous IL-2 treatment.
Design:
- Participants will be screened with a physical examination and medical history, tumor
imaging studies, and heart and lung function tests.
- Prior to treatment, participants will have an intravenous catheter inserted into the
chest to administer the study drugs.
- Participants will have leukapheresis to provide white blood cells for laboratory
modification.
- Seven days before the start of the treatment, participants will be admitted to the
hospital to have chemotherapy with cyclophosphamide and fludarabine. These drugs will
suppress the immune system to improve the effects of the treatment.
- One to four days after the last dose of chemotherapy, participants will receive the
modified cells. Participants in the group that will receive IL-2 will begin to receive
the treatment 24 hours after the cell infusion, every day for 5 days. All participants
will receive filgrastim injections to help the body produce more white blood cells.
- Participants will recover in the hospital for about 7 to 12 days after the cell
infusion or the last dose of IL-2. Participants will continue to receive medications
and provide blood and tumor samples for testing.
- Participants will have regular followup visits to assess the effects of the treatment.
Background:
- 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.
Objectives:
- 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.
Eligibility:
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
Design:
- 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
subsequent aldesleukin.
- 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
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