临床试验/NCT00358657

NCT00358657终止2 期

HLA-Haploidentical Related Marrow Grafts for the Treatment of Primary Immunodeficiencies and Other Nonmalignant Disorders Using Conditioning With Low-Dose Cyclophosphamide, TBI and Fludarabine and Postgrafting Cyclophosphamide

Fred Hutchinson Cancer Center3 个研究点分布在 1 个国家目标入组 14 人开始时间: 2006年5月24日最近更新: 2021年1月26日

适应症

干预措施

试验速览

阶段: 2 期
状态: 终止
发起方: Fred Hutchinson Cancer Center
入组人数: 14
试验地点: 3
主要终点: Graft Rejection

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

This phase I/II trial studies the side effects of fludarabine phosphate, cyclophosphamide and total-body irradiation followed by donor bone marrow transplant and cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus in treating patients with primary immunodeficiency disorders or noncancerous inherited disorders. Giving low doses of chemotherapy and total-body irradiation before a bone marrow transplant helps prepare the patient's body to accept the incoming donor's bone marrow and decrease the risk that the patient's immune system will reject the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's bone marrow make stem cells, red blood cells, white blood cells, and platelets. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells called graft versus host disease. Giving cyclophosphamide, mycophenolate mofetil, tacrolimus, and sirolimus after the transplant may help decrease this from happening.

详细描述

PRIMARY OBJECTIVE:

I. Determine safety of nonmyeloablative conditioning and hematopoietic cell transplantation (HCT) from human leukocyte antigen (HLA)-haploidentical related donors for patients with nonmalignant inherited disorders who do not have an HLA-matched related or unrelated donor.

SECONDARY OBJECTIVES:

I. Determine whether nonmyeloablative conditioning and HCT from an HLA-haploidentical related donor graft can establish mixed chimerism (> 5% cluster of differentiation [CD]3+ donor T-cell chimerism) in patients with nonmalignant inherited disorders.

II. Transplant related mortality at day 100.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: — 至 55 Years（Child, Adult）
性别: All
接受健康志愿者: 否

入选标准

•Primary immunodeficiency disorder or other nonmalignant inherited disease (except Fanconi anemia) treatable by allogeneic HCT
•Patients with pre-existing medical conditions or other factors that renders them at high risk for regimen related toxicity or ineligible for conventional myeloablative HCT and who do not have HLA-matched related or unrelated donors
•Patients with a related donor who is identical for one HLA haplotype
•Acquired aplastic anemia: severe aplastic anemia (SAA) is defined as follows:
•Bone marrow cellularity < 25%, or marrow cellularity < 50% but with < 30% residual hematopoietic cells
•Two out of three of the following (in peripheral blood): neutrophils < 0.5 x 10^9/L; platelets < 20 x 10^9/L; reticulocytes < 20 x 10^9/L
•SAA diagnostic criteria may be applied to assessment at initial diagnosis or follow-up assessments
•DONOR: Related donors who are identical for one HLA haplotype
•DONOR: Bone marrow will be the only allowed stem cell source

排除标准

•Fanconi anemia
•Suitably HLA-matched related or unrelated donors
•Patients with metabolic storage diseases who have severe central nervous system (CNS) involvement of disease, defined as intelligence quotient (IQ) score < 70
•Cardiac ejection fraction < 30% (or, if unable to obtain ejection fraction, shortening fraction < 26%) on multiple-gated acquisition (MUGA) scan or cardiac echocardiogram (echo), symptomatic coronary artery disease, or other cardiac failure requiring therapy; patients with a history of, or current cardiac disease should be evaluated with appropriate cardiac studies and/or cardiology consult; patients with a shortening fraction of < 26% must be seen by cardiology for approval
•Poorly controlled hypertension despite anti-hypertensive medications
•Patients with clinical or laboratory evidence of liver disease will need to be evaluated for the cause of the liver disease, its clinical severity in terms of liver function and the degree of portal hypertension; patients will be excluded if they are found to have fulminant liver failure, cirrhosis of the liver with evidence of portal hypertension, bridging fibrosis, alcoholic hepatitis, esophageal varices, a history of bleeding esophageal varices, hepatic encephalopathy, uncorrectable hepatic synthetic dysfunction evidenced by prolongation of the prothrombin time, ascites related to portal hypertension, bacterial or fungal liver abscess, biliary obstruction, chronic viral hepatitis with total serum bilirubin > 3 mg/dl, or symptomatic biliary disease
•Positive for human immunodeficiency virus (HIV)
•Females who are pregnant (beta-human chorionic gonadotropin positive [beta-HCG+]) or breast-feeding
•Fertile men or women who are unwilling to use contraceptives during HCT and up to 12 months post-treatment
•Patients with fungal pneumonia with radiological progression after receipt of amphotericin formulation or mold-active azoles for greater than 1 month will not be eligible for this protocol (either regimen A or B)
•DONOR: Donor-recipient pairs in which the HLA-mismatch is only in the host-versus-graft (HVG) direction; patients are homozygous and donor is heterozygous
•DONOR: Donors who are not expected to meet the minimum target dose of marrow cells (1 x 10^8 nucleated cells/kg recipient ideal body weight)
•DONOR: HIV-positive donors
•DONOR: A positive anti-donor cytotoxic cross match is absolute donor exclusion
•DONOR: < 6 months old and > 75 years old

Number of patients with graft rejection (CD3 donor chimerisms \<5%).

Graft Failure

时间窗: Day 84

Number of patients with graft failure (grade IV thrombocytopenia and neutropenia after day 21 that lasts \> 2 weeks andn is refractory to growth factor support).

次要结局

Proportion of Patients Who Achieve Greater Than 5% Donor T-cell Chimerism(By day 84)
Incidence of Grade I/II Acute Graft Versus Host Disease (GVHD)(Day 100 post transplant)
Number of Patients With Transplant Related Mortality(Day 100 post transplant)
Incidence of Grade III/IV Acute Graft Versus Host Disease (GVHD)(Day 100 post transplant)
Immune Reconstitution(1 year post transplant)
Number of Patients With Infections(Through day 200 after HCT)
Incidence of Chronic GVHD(1 year post transplant)

研究者

发起方

Fred Hutchinson Cancer Center

申办方类型

Other

责任方

Principal Investigator

主要研究者

Kanwaldeep K Mallhi

Assistant Professor, Clinical Research Division, Fred Hutch

Fred Hutchinson Cancer Center

研究点 (3)

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