A Phase II Study of HLA-Matched Peripheral Blood Mobilized Hematopoietic Progenitor Cell Transplantation for Metastatic Renal Cell Carcinoma Followed by Allogeneic T-Cell Infusion as Adoptive Immunotherapy
HLA Matched Peripheral BLood Stem Cells
Urogenital Diseases+13
+ Adenocarcinoma
+ Carcinoma
Treatment Study
Summary
Study start date: February 9, 1998
Actual date on which the first participant was enrolled.OBJECTIVES: Determine the antitumor effect of allogeneic peripheral blood stem cell transplantation (PBSCT) in patients with metastatic renal cell carcinoma. Evaluate the safety and toxicity of a nonmyeloablative, low-intensity, preparative regimen followed by an HLA-matched allogeneic PBSCT in these patients. Determine engraftment by measuring donor-recipient chimerism in lymphoid and myeloid lineages in patients treated with this regimen. Determine the relationship between donor-host chimerism and the incidence of acute and chronic graft-versus-host disease in patients treated with this regimen. Determine the effect of lymphocyte infusions on donor-host chimerism in this patient population. Determine the response rate, disease-free survival, overall survival, and mortality from the procedure or tumor progression in patients treated with this regimen. OUTLINE: Nonmyeloablative preparative regimen: Patients receive 1 of 3 preparative regimens prior to peripheral blood progenitor cell (PBPC) transplantation. (Regimens 2 and 3 closed to accrual as of 10/1/03.) Regimen 1: Patients receive cyclophosphamide IV over 1 hour on days -7 and -6 and fludarabine IV over 30 minutes on days -5 to -1. Regimen 2 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour on days -7 and -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2. Regimen 3 (closed to accrual as of 10/1/03): Patients receive cyclophosphamide IV over 1 hour on days -8 to -6, fludarabine IV over 30 minutes on days -5 to -1, and antithymocyte globulin on days -5 to -2. PBPC transplantation: Patients undergo mobilized CD34+ PBPC transplantation on day 0. PBPC transplantation may be repeated on days 1 and 2, if deemed necessary. Graft-versus-host disease (GVHD) prophylaxis: Patients receive 1 of 3 GVHD prophylaxis regimens. Regimen 1 (closed to accrual as of 10/17/00): Patients receive cyclosporine IV over 12 hours or orally beginning on day -4 and continuing for up to approximately 3 months. Regimen 2 (open to accrual from 10/17/00 through 2/11/02): Patients receive cyclosporine as in regimen 1. Patients also receive mycophenolate mofetil. Regimen 3 (open to accrual as of 2/11/02): Patients receive cyclosporine as in regimen 1. Patients also receive methotrexate. Donor lymphocyte infusions: Patients with progressive disease on days 15-30, day 60, or day 100, without GVHD, receive infusion(s) of donor lymphocytes. Further donor lymphocyte infusions after day 100 may be given at the discretion of the attending physician. Patients are followed every 2 months for 6 months, every 3 months for 2 years, and then every 6 months for 2½ years. PROJECTED ACCRUAL: A total of 80 patients will be accrued for this study.
Protocol
This section provides details of the study plan, including how the study is designed and what the study is measuring.156 patients to be enrolled
Total number of participants that the clinical trial aims to recruit.Treatment Study
Eligibility
Researchers look for people who fit a certain description, called eligibility criteria: person's general health condition or prior treatments.Any sex
Biological sex of participants that are eligible to enroll.From 18 to 80 Years
Range of ages for which participants are eligible to join.Healthy volunteers not allowed
If individuals who are healthy and do not have the condition being studied can participate.Conditions
Pathology
Criteria
INCLUSION CRITERIA - PATIENT: Ages 18-80 years. Biopsy proven metastatic RCC, not amenable to complete surgical resection, progressive bidimensionally evaluable clinically or radiographically. No prior treatment for RCC within 30 days. HIV negative. ECOG performance status of 1 or less. No major organ dysfunction precluding transplantation. DLCO greater than or equal to 65% predicted. Left ventricular ejection fraction greater than or equal to 40%. HLA 6/6 or 5/6 matched family related donor available. Ability to comprehend the investigational nature of the study and provide informed consent. Durable power of attorney signed. INCLUSION CRITERIA - DONOR: HLA 6/6 or 5/6 matched family related donor. Fit to receive G-CSF and give peripheral blood stem cells (normal blood counts, normotensive, no history of stroke). Ability to comprehend the investigational nature of the study and provide informed consent. Ages 18-80. EXCLUSION CRITERIA (any of the following) - PATIENT: Patient Pregnant. Age greater than 80 or less than 18 years. ECOG performance status of 2 or more. Psychiatric disorder or mental deficiency of the patient or donor sufficiently severe as to make compliance with the BMT treatment unlikely, and making informed consent impossible. Major anticipated illness or organ failure incompatible with survival from BMT where survival is considered insufficient to assess transplant outcome (i.e. less than 3 months). DLCO less than 65% predicted. Left ventricular ejection fraction less than 40%. Serum creatinine greater than 2.5mg/dl or creatinine clearance less than 50 cc/min by 24 hour urine collection. Serum bilirubin greater than 4 mg/dl, transaminases greater than 3 x upper limit of normal. HIV positive. History of other malignancies except basal cell or squamous carcinoma of the skin. Disease which is limited and amenable to complete surgical resection. Lack of evidence for progressive disease. Disease which is not evaluable clinically or radiographically. Evidence for CNS metastatic disease. Disease involving greater than 25% of the liver radiographically. Hypercalcemia (greater than 2.5 mmol/L). EXCLUSION CRITERIA - DONOR: Donor pregnant or lactating. Donor HIV or HBsAg positive. History of malignancy within 5 years except basal cell or squamous carcinoma of the skin. Donor unfit to receive G-CSF and undergo apheresis (Uncontrolled hypertension, history of stroke, thrombocytopenia).
Study Plan
Find out more about all the medication administered in this study, their detailed description and what they involve.One single intervention group is designated in this study
This study does not include a placebo group
Treatment Groups
Group I
ExperimentalStudy Objectives
Primary Objectives
Secondary Objectives
Study Centers
These are the hospitals, clinics, or research facilities where the trial is being conducted. You can find the location closest to you and its status.This study has 1 location
NIH - Warren Grant Magnuson Clinical Center
Bethesda, United StatesOpen NIH - Warren Grant Magnuson Clinical Center in Google Maps