Track topics on Twitter Track topics that are important to you
RATIONALE: An infusion of a patient's lymphocytes that have been treated in the laboratory to remove certain immune cells may be an effective treatment for melanoma. Drugs, such as cyclophosphamide and fludarabine, may suppress the immune system so that the patient's immune cells allow the infused lymphocytes to work. Interleukin-2 may help the lymphocytes kill more tumor cells when they are put back in the body. Giving cyclophosphamide and fludarabine followed by an autologous lymphocyte infusion and interleukin-2 may kill more tumor cells.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide and fludarabine followed by an autologous lymphocyte infusion and interleukin-2 works in treating patients with refractory or recurrent melanoma.
- Determine tumor regression in patients with metastatic melanoma treated with nonmyeloablative lymphodepleting chemotherapy comprising cyclophosphamide and fludarabine followed by autologous CD25-positive-T-regulatory-cell-depleted lymphocyte reinfusion and high-dose interleukin-2.
- Determine the rate of repopulation of CD25-positive T-regulatory cells in patients treated with this regimen.
- Determine the toxicity of this regimen in these patients.
- Apheresis and CD25-positive T-regulatory cell depletion: Patients undergo 1-2 aphereses to collect peripheral blood mononuclear cells (PBMC). CD25-positive T-regulatory cells are depleted from the collected PBMC in vitro.
- Nonmyeloablative lymphodepleting chemotherapy: Patients receive cyclophosphamide IV over 1 hour on days -8 and -7 and fludarabine IV over 15-30 minutes on days -6 to -2.
- Autologous CD25-positive-T-regulatory-cell-depleted lymphocyte reinfusion: Patients receive autologous lymphocytes IV over 20-30 minutes on day 0.
- Filgrastim (G-CSF) and high-dose interleukin-2 (IL-2) therapy: Patients receive G-CSF subcutaneously (SC) daily beginning on day 0 and continuing until blood counts recover. Patients also receive high-dose IL-2 IV over 15 minutes 3 times daily on days 0-4 and 14-18. Patients are reevaluated 4-6 weeks after completion of high-dose IL-2 therapy. Patients achieving stable disease or a partial response may receive additional high-dose IL-2 as above for up to 2 retreatment courses in the absence of disease progression or unacceptable toxicity. Retreatment begins at least 6 weeks after autologous lymphocyte reinfusion.
After completion of study treatment, patients are followed at 4-6 weeks and then every 1-2 months thereafter.
PROJECTED ACCRUAL: A total of 16-29 patients will be accrued for this study within 1-1.5 years.
Masking: Open Label, Primary Purpose: Treatment
aldesleukin, filgrastim, therapeutic autologous lymphocytes, cyclophosphamide, fludarabine phosphate
NCI - Surgery Branch
Active, not recruiting
National Cancer Institute (NCI)
Published on BioPortfolio: 2014-08-27T03:52:09-0400
RATIONALE: Treating lymphocytes in the laboratory may help the lymphocytes kill more tumor cells when they are put back in the body. Aldesleukin may stimulate the lymphocytes to kill tumor...
Chemotherapy Consisting of Fludarabine and Cyclophosphamide Followed By White Blood Cell Infusion, Vaccine Therapy, and Aldesleukin in Treating Patients With Recurrent or Refractory Metastatic Melanoma
RATIONALE: Drugs used in chemotherapy, such as fludarabine and cyclophosphamide, work in different ways to stop tumor cells from dividing so they stop growing or die. Treated white blood c...
RATIONALE: Aldesleukin may stimulate lymphocytes to kill melanoma cells. Treating lymphocytes with interleukin-21 in the laboratory may help the lymphocytes kill more tumor cells when they...
RATIONALE: Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Bi...
RATIONALE: Inserting a laboratory-treated gene into a person's white blood cells may make the body build an immune response to kill tumor cells. Giving cyclophosphamide and fludarabine bef...
To evaluate the impact of systemic cyclophosphamide treatment on the rat uterus and investigate the potential therapeutic effects of natural antioxidant preparations curcumin and capsaicin against cyc...
Toxicity of carmustine and cyclophosphamide can cause pulmonary injury after hematopoietic stem cell transplantation.
The superficial digital flexor tendon (SDFT) is a structure frequently affected by injuries in high-performance athletic horses, and there are limited therapeutic options. Regenerative medicine has ev...
Analysis of changes in lymphocyte subpopulations during co-culturing with multipotent mesenchymal stromal cells (MSC) revealed two distinct MSC groups: one group (A) increased HLA-DR expression on lym...
fingolimod, a disease-modifying treatment licenced (FDA approved in 2010) for relapsing-remitting multiple sclerosis (RRMS), is a modulator for four of the five known sphingosine-1-phosphate (S1P) rec...
Lymphocytes that show specificity for autologous tumor cells. Ex vivo isolation and culturing of TIL with interleukin-2, followed by reinfusion into the patient, is one form of adoptive immunotherapy of cancer.
Precursor of an alkylating nitrogen mustard antineoplastic and immunosuppressive agent that must be activated in the LIVER to form the active aldophosphamide. It has been used in the treatment of LYMPHOMA and LEUKEMIA. Its side effect, ALOPECIA, has been used for defleecing sheep. Cyclophosphamide may also cause sterility, birth defects, mutations, and cancer.
An enzyme of the transferase class that catalyzes the conversion of sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to D-ribose 5-phosphate and D-xylulose 5-phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 184.108.40.206.
An enzyme of the transferase class that catalyzes the reaction sedoheptulose 7-phosphate and D-glyceraldehyde 3-phosphate to yield D-erythrose 4-phosphate and D-fructose phosphate in the PENTOSE PHOSPHATE PATHWAY. (Dorland, 27th ed) EC 220.127.116.11.
A critical subpopulation of regulatory T-lymphocytes involved in MHC Class I-restricted interactions. They include both cytotoxic T-lymphocytes (T-LYMPHOCYTES, CYTOTOXIC) and CD8+ suppressor T-lymphocytes.
Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells. In vertebrates, it is composed of blo...
Bladder Cancer Brain Cancer Breast Cancer Cancer Cervical Cancer Colorectal Head & Neck Cancers Hodgkin Lymphoma Leukemia Lung Cancer Melanoma Myeloma Ovarian Cancer Pancreatic Cancer ...