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Clinical Trial Name - Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin After Cyclophosphamide and Fludarabine in
| Original Study ID : CDR0000557605 |
| Secondary ID : Array |
| NCT ID : NCT00513604 |
| Brief Title : Tumor-Infiltrating Lymphocytes and High-Dose Aldesleukin After Cyclophosphamide and Fludarabine in Treating Patients With Metastatic Melanoma |
| Official Title : A Phase II Study Using Short-Term Cultured Anti-Tumor Autologous Lymphocytes Following a Lymphocyte Depleting Regimen in Metastatic Melanoma |
| Brief Summary : RATIONALE: Tumor-infiltrating lymphocytes are white blood cells that are removed from a tumor and given back to a patient to help the body fight cancer. Colony-stimulating factors, such as aldesleukin, increase the number of white blood cells and platelets found in bone marrow or peripheral blood. Drugs used in chemotherapy help kill tumor cells and prepare the patient's body for the tumor-infiltrating lymphocytes and aldesleukin. Giving tumor-infiltrating lymphocytes together with aldesleukin after combination chemotherapy may kill more tumor cells. PURPOSE: This phase II trial is studying the side effects and how well giving tumor-infiltrating lymphocytes together with high-dose aldesleukin after cyclophosphamide and fludarabine works in treating patients with metastatic melanoma. |
| Source : National Cancer Institute (NCI) |
| Detailed Description : OBJECTIVES: Primary - Determine the ability of the administration of autologous, tumor-infiltrating lymphocytes (TIL) infused after minimal in vitro culture in conjunction with high-dose aldesleukin (IL-2) after a non-myeloablative lymphodepleting preparative regimen to mediate tumor regression in patients with metastatic melanoma. - Determine the ability of the administration of autologous, TIL infused after minimal in vitro culture in conjunction with high dose aldesleukin after chemoradiation lymphodepleting regimen to mediate complete tumor regression in these patients. - Determine the toxicity of this treatment regimen. Secondary - Determine the rate of repopulation of the young TIL cells in treated patients and establish in vitro correlates of TIL cultures that mediate objective response and in vivo persistence. OUTLINE: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine phosphate IV over 30 minutes on days -5 to -1, and aldesleukin IV over 15 minutes every 8 hours on days 0-4. Patients undergo autologous CD34+ cell depleted tumor-infiltrating lymphocyte infusion over 20-30 minutes on day 0. Patients may also receive filgrastim (G-CSF) subcutaneously on days 1-4 until blood counts recover. Some patients receive total-body irradiation twice on day -2 and once on day -1. Some patients with stable disease or who have achieved a partial response or recurrence after response may receive one retreatment course beginning approximately 8 weeks after the first infusion in the absence of disease progression or unacceptable toxicity. Blood is collected periodically during study for research studies. Samples are assessed by cytolysis assays, cytokine release, limiting-dilution analysis, intracellular FACS, and Elispot assays. Measurement of CD4 and CD8 T cells will be conducted and studies of cell persistence in circulation will be conducted using PCR assays. |
| Overall Status : Recruiting |
| Start Date : June 2007 |
| Official Title : Phase 2 |
| Phase : Interventional |
| Study Design : Treatment, Open Label |
| Enrollment : 138 |
| Verification Date : October 2008 |
| First Received Date : August 6, 2007 |
| Trial Eligibility |
| Criteria : DISEASE CHARACTERISTICS: Inclusion criteria: - Measurable metastatic melanoma with at least one lesion that is resectable for tumor-infiltrating lymphocytes (TIL) generation - TILs collected on Surgery Branch protocol NCI-03-C-0277 or another IRB-approved adoptive cell therapy (e.g., NCI-99-C-0158 or NCI-03-C-0162) must be available - Patients with one or more brain metastases less than 1 cm each and any patient with 1 or 2 brain metastases greater than 1 cm must have been treated and stable for 3 months Exclusion criteria: - Patients eligible for Surgery Branch clinical protocol NCI-06-C-0136 as long as it remains open to accrual - Any of the following for patients in cohort 3 only: - Prior radiotherapy which makes the patient ineligible to receive 600 cGy - Inability to mobilize CD34+ cells PATIENT CHARACTERISTICS: Inclusion criteria: - Not pregnant or nursing - Negative pregnancy test - Fertile patients must use effective contraception during and for 4 months after completion of study treatment - Life expectancy > 3 months - ECOG performance status 0-1 - ANC > 1,000/mm³ (without filgrastim [G-CSF] support) - WBC > 3,000/mm³ - Hemoglobin > 8.0 g/dL - Platelet count > 100,000/mm³ - Seronegative for HIV antibody - Seronegative for hepatitis B or hepatitis C - Serum ALT/AST < 3 times upper limit of normal - Serum creatinine ≤ 1.6 mg/dL - Total bilirubin ≤ 2 mg/dL (< 3 mg/dL for patients with Gilbert's syndrome) Exclusion criteria: - Active systemic infections, coagulation disorders, or other active major medical illnesses of the cardiovascular, respiratory, or immune system as evidenced by a positive stress thallium or comparable test - Myocardial infarction, cardiac arrhythmias, or obstructive or restrictive pulmonary disease - Any form of primary immunodeficiency (i.e., severe combined immunodeficiency disease or AIDS) - Opportunistic infections - History of severe immediate hypersensitivity reaction to any of the agents used in this study - History of coronary revascularization or ischemic symptoms - Known LVEF ≤ 45% in any patient or documented in patients with clinically significant atrial and/or ventricular arrhythmias, including, but not limited to, any of the following, or patients ≥ 60 years of age: - Atrial fibrillation - Ventricular tachycardia - Second- or third-degree heart block - Documented FEV_1 ≤ 60% of predicted in patients with a prolonged history of cigarette smoking or symptoms of respiratory dysfunction PRIOR CONCURRENT THERAPY: Inclusion criteria: - More than 4 weeks since any prior systemic therapy and recovered from prior toxicity to ≤ grade 1 (except for toxicities such as alopecia or vitiligo) - Patients may have undergone minor surgical procedures within the past 3 weeks, as long as all toxicities have recovered to ≤ grade 1 - At least 6 weeks since any prior anti-CTLA4 antibody therapy - Patients who have previously received any anti-CTLA4 antibody must have a normal colonoscopy with normal colonic biopsies Exclusion criteria: - See Disease Characteristics - Concurrent systemic steroid therapy |
| Gender : Both |
| Minimum Age : 18 Years |
| Maximum Age : N/A |
| Healthy Volunteers : No |
| Facilities |
| Facility Name : Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office |
| Status : Recruiting |
| City : Bethesda |
| State : Maryland |
| Zip Code : 20892-1182 |
| Country : United States |
| OutComes |
| Primary OutComes |
| Secondary OutComes |
| Measure : Rate of lymphocyte cell repopulation |
| Safety issue : No |
| Measure : In vitro immunological correlates that predict in vivo persistence and clinical response |
| Safety issue : No |
| Interventions |
| Type : Biological |
| Name : aldesleukin |
| Type : Biological |
| Name : therapeutic autologous lymphocytes |
| Type : Drug |
| Name : cyclophosphamide |
| Type : Drug |
| Name : fludarabine phosphate |
| Type : Genetic |
| Name : polymerase chain reaction |
| Type : Other |
| Name : immunologic technique |
| Type : Other |
| Name : laboratory biomarker analysis |
| Type : Radiation |
| Name : total-body irradiation |
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