Clinical Trials Logo

Clinical Trial Summary

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.


Clinical Trial Description

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. ;


Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT01271907
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Terminated
Phase Phase 2
Start date December 2010
Completion date April 2012

See also
  Status Clinical Trial Phase
Active, not recruiting NCT02506153 - Physician/Patient Choice of Either High-Dose Recombinant Interferon Alfa-2B or Ipilimumab, Versus Pembrolizumab in Treating Patients With Stage III-IV High Risk Melanoma That Has Been Removed by Surgery Phase 3
Withdrawn NCT05572463 - A Platform Study of Novel Immunotherapy Products in Participants With Previously Treated Unresectable or Metastatic Cutaneous Melanoma Phase 1/Phase 2
Not yet recruiting NCT06391099 - Ketogenic Dietary Intervention to Improve Response to Immunotherapy in Patients With Metastatic Melanoma and Metastatic Kidney Cancer N/A
Recruiting NCT06265285 - Comparison of In-Home Versus In-Clinic Administration of Subcutaneous Nivolumab Through Cancer CARE (Connected Access and Remote Expertise) Beyond Walls (CCBW) Program Phase 2
Recruiting NCT05098210 - Personalized Neo-Antigen Peptide Vaccine for the Treatment of Stage IIIC-IV Melanoma or Hormone Receptor Positive Her2 Negative Metastatic Refractory Breast Cancer Phase 1
Recruiting NCT04511013 - A Study to Compare the Administration of Encorafenib + Binimetinib + Nivolumab Versus Ipilimumab + Nivolumab in BRAF-V600 Mutant Melanoma With Brain Metastases Phase 2
Recruiting NCT04812470 - Hepatic Arterial Infusion of Autologous Tumor Infiltrating Lymphocytes in Patients With Melanoma and Liver Metastases Phase 1
Not yet recruiting NCT05903937 - Locoregional Administration of TIL and Lymphodepletion in Patients With Melanoma and Liver Metastases Phase 1
Recruiting NCT04375527 - Binimetinib and Nivolumab for the Treatment of Locally Advanced Unresectable or Metastatic BRAF V600 Wildtype Melanoma Phase 2