A Phase I/II Open Label, Dose Escalation Study of Palifermin (Kepivance) in Persons Undergoing Unrelated Donor Allogeneic Hematopoietic Cell Transplantation

National Cancer Institute (NCI)2 个研究点分布在 1 个国家目标入组 34 人开始时间: 2015年9月24日最近更新: 2025年9月30日

适应症

干预措施

试验速览

阶段: 1 期
状态: 已完成
发起方: National Cancer Institute (NCI)
入组人数: 34
试验地点: 2
主要终点: Phase II: Estimated Percent of Participants Who Experienced Severe Chronic Graft Versus Host Disease (GVHD)

研究概览研究设计入排标准研究组 & 干预措施结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Background:

- In allogeneic stem cell transplantation (SCT), stem cells are taken from a donor and given to a recipient. Sometimes the recipient's immune system destroys the donors' cells. Or donor immune cells attack the recipient's tissues, called graft-versus-host disease (GVHD). This is less likely when the recipient and donor have similar human leukocyte antigens (HLA). Researchers want to see if the drug palifermin improves the results of allogeneic SCT from HLA-matched unrelated donors.

Objective:

- To see if high doses of palifermin before chemotherapy are safe, prevent chronic GVHD, and improve immune function after transplant.

Eligibility:

- Adults 18 years of age or older with blood or bone marrow cancer with no HLA-matched sibling donor, but with a HLA-matched unrelated donor.

Description of Research Study:

Participants will be screened with medical history, physical exam, and blood and urine tests. They will have scans and heart and lung exams.
Before transplant, participants will:
Have many tests and exams. These include blood tests throughout the study and bone marrow biopsy.
Get a central line catheter if they do not have one.
Have 1-3 rounds of chemotherapy.
Have more tests to make sure they can have the transplant, including medical history, physical exam, blood tests, disease specific restaging.
Get palifermin by intravenous (IV) and conditioning chemotherapy to prepare for hematopoietic stem cell transplantation (HSCT). They will get other drugs; some they will take at least 6 months.
Participants will get the HSCT.
After transplant, participants will:
Be hospitalized at least 3-4 weeks.
Monitored at least weekly for the first 100 days.
Stay near District of Columbia (D.C). for approximately 100 days post-transplant.
After 100 days post-transplant - visit National Institutes of Health (NIH) 5 times the first 2 years, then yearly until 5 years post-transplant.
Additional tests/procedures may be performed to monitor safety, response to transplant, side effects.

详细描述

Background:

Graft versus host disease (GVHD) and impaired immune reconstitution are major transplant complications and barriers to improving outcomes after allogeneic hematopoietic stem cell transplantation (alloHSCT) for hematologic malignancies. GVHD is initiated when donor T-cells become alloreactive against recipient major or minor histocompatibility antigens. This process may be exacerbated during the transplantation process by exposure of tissue antigens to donor T-lymphocytes after chemotherapy-induced injury.
Palifermin, a recombinant keratinocyte growth factor-1 (KGF-1), imitates the actions of intrinsic KGF and binds to the Fibroblast growth factor (FGF) receptor 2b, which is expressed in the epidermis, oral mucosa, gastrointestinal (GI) mucosa and urothelium, thereby increasing the regenerative capacity of these tissues. Palifermin has been shown to reduce the duration and severity of oral mucositis after intensive chemo-radiotherapy and autologous HSCT for hematologic cancers and is Food and Drug Administration (FDA) approved. In pre-clinical studies, palifermin has been shown to have an effect on control of acute or chronic GVHD and immune reconstitution after alloHSCT. However, subsequent clinical studies in alloHSCT indicate that the dose and schedule of palifermin as currently

used in humans does not optimize its activity in terms of prevention of GVHD or thymus recovery following alloHSCT.

- We hypothesize that higher doses of palifermin in the immediate pre alloHSCT conditioning setting will lead to enhanced thymopoiesis, decreased chronic GVHD, and improved immune reconstitution. A dose escalation study is necessary to determine safe dosing levels in persons undergoing alloHSCT.

Objectives:

研究设计

研究类型: Interventional
分配方式: Non Randomized
干预模型: Sequential
主要目的: Treatment
盲法: None

入排标准

年龄范围: 18 Years 至 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Verification of donor eligibility (clearance must be received from the NMDP)
•Donors are evaluated by NMDP affiliated donor centers per NMDP Standards.
•Donors who are medically suitable, but ineligible by Food and Drug Administration (FDA) guidelines may still donate peripheral blood stem cells (PBSC) with documentation of urgent medical need by the PI.
•Patients who receive stem cell products from ineligible donors will be informed of any increase in risk of transfusion-related diseases prior to initiation of conditioning chemotherapy.
•Donors who are ineligible or unwilling to donate bone marrow will not be eligible to donate to study recipients. However, in the event that the patient has already begun conditioning chemotherapy and a donor PBSC collection is terminated early for donor-related medical concerns, a bone marrow graft may be infused. Should this occur, the recipient will continue to be managed on this protocol for all transplant-related care and complications. Patient will stay on study, but clinical outcomes will not be eligible for the statistics and end point calculations.
•Inadequate stem cell collection from the selected donor is defined as less than or equal to 2 x 10^6 cluster of differentiation 34 (CD34+) cells/kg. In most cases, donor cell collections are infused fresh. If a fresh collection is found to have an inadequate cell count, the cells will still be infused, but the recipient will be removed from the study and managed clinically for all transplant related care and complications on this protocol. If the patient fails to engraft, the donor may be requested for a second collection or an emergency bone marrow harvest at the discretion of the PI and NMDP Medical Director. In the event of an inadequate collection obtained prior to patient conditioning, the donor may be asked to donate a second time, or another eligible donor may be requested.
•Renal and hepatic function continues to meet eligibility criteria, reassessed as follows:
•24-hour creatinine clearance or calculated (using the Cockcroft-Gault formula) creatinine clearance > 60 mL/min/1.73 m^2 (induction phase only)
•(((140-age)*mass(kg))/(72*serum creatinine (mg/dL))) x 1.73 m^2/patients body surface area (BSA)
•If the patient is female, multiply the above by 0.85
•In patients with suspected liver disease, bilirubin must be less than or equal to 2.5 mg/dL, AST and ALT must be less than or equal to 2.5 times institutional upper limit of normal (ULN)
•The malignancy must be restaged prior to research phase and must not have progressed during induction chemotherapy (stable disease or better). Persons with acute leukemia, myelodysplastic syndrome (MDS)/refractory anemia with excess blasts (RAEB)-I or II or chronic myeloid leukemia (CML) with previous accelerated or blast phase must have <5% blasts in the bone marrow. Persons with chronic phase CML may have up to 10% blasts in the bone marrow.
•EXCLUSION CRITERIA (applies to all phases of this protocol):
•Active infection that is not responding to antimicrobial therapy.
•Active central nervous system (CNS) involvement by malignancy (patients with known positive cerebrospinal fluid (CSF) cytology or parenchymal lesions visible by computed tomography (CT) or magnetic resonance imaging (MRI).
•Previous other malignancies unless they have undergone curative intent therapy for that malignancy and (1) have had no evidence of that disease for 5 years, and/or (2) be deemed at low risk for recurrence (less than or equal to 20% at 5 years).
•Human immunodeficiency virus (HIV) positive patients are ineligible as allogeneic stem cell transplant is not yet a proven approach in this patient population, and patients are at increased risk of lethal infections when treated with marrow suppressive therapy.
•Pregnant women are excluded from this study because palifermin has been shown to be embryotoxic and fetotoxic in animal studies. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with palifermin, breastfeeding should be discontinued for the duration of active study therapy. These potential risks may also apply to other agents used in this study.
•History of psychiatric disorder or any other condition which may compromise compliance with transplant protocol or expose patient to unnecessary risk as determined by principal investigator or lead associate investigator.

排除标准

未提供