Phase I Clinical Trial Using an Engineered Peripheral Blood Graft for Haploidentical Transplantation
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Incidence of treatment failure defined as primary graft failure, grade 3-4 acute graft versus host disease (aGVHD), or non-relapse mortality
研究概览
简要总结
This pilot phase I trial studies the side effects of engineered donor stem cell transplant in treating patients with hematologic malignancies. Sometimes the transplanted cells from a donor can make an immune response against the body's normal cells (called graft-versus-host disease). Using T cells specially selected from donor blood in the laboratory for transplant may stop this from happening.
详细描述
PRIMARY OBJECTIVE:
I. To assess the safety of a modified peripheral blood (PB) graft for haploidentical transplantation, obtained by using depletion of naive, cluster of differentiation (CD)45RA+ T cells.
SECONDARY OBJECTIVES:
I. To estimate the proportion of patients with engraftment/graft failure. II. To determine the day 100 and 6 month non-relapse mortality (NRM). III. To estimate the cumulative incidence of grade 2-4 and 3-4 acute graft versus (vs.) host disease (aGVHD).
IV. To assess the rate of chronic GVHD within the first year post transplantation.
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
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Lack of a human leukocyte antigen (HLA) matched related donor, lack of an immediately available 8/8 HLA matched unrelated donor
- •Patients must be diagnosed with a high-risk and/or advanced hematologic malignancy defined as one of the following
- •Acute lymphocytic leukemia (ALL) in complete remission (CR)1 with high-risk features including adverse cytogenetic such as t(9;22), t(1;19), t(4;11), or MLL gene rearrangements; in second or greater morphologic remission; persistent minimal residual disease
- •Acute myeloid leukemia (AML) in CR1 with intermediate-risk disease and persistent detectable minimal residual disease (MRD), or with high-risk features defined as: greater than 1 cycle of induction therapy required to achieve remission; preceding myelodysplastic syndrome (MDS) or myeloproliferative disease; presence of FLT3 mutations or internal tandem duplications, DNMT3a, TET2, MLL-partial tandem duplication (PTD), ASXL1, PHF6; FAB M6 or M7 classification; adverse cytogenetics including: -5, del 5q, -7, del7q, abnormalities involving 3q, 9q, 11q, 20q, 21q, 17, +8, complex (> 3 abnormalities)
- •Patients with AML must have less than 10% bone marrow blasts and < 100/mcL absolute peripheral blood blast count
- •Patients with AML in CR2, subsequent CR or with active disease at transplant (< 10% bone marrow blasts)
- •MDS with International Prognostic Scoring System (IPSS) intermediate-2 or higher, therapy-related MDS or chronic myelomonocytic leukemia (CMML)
- •Aplastic anemia with absolute neutrophil count (ANC) < 1,000 and transfusion dependent after failed immunosuppression therapy
- •Chronic myeloid leukemia (CML) >= 1st chronic phase, after failed >=2 lines of tyrosine kinase inhibitors; patients who progressed to blast phase must be in morphologic remission at transplant
- •Relapsed Hodgkin's disease or non-Hodgkin's lymphoma (NHL)
- •Patients with chemo-sensitive chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) with persistent or recurrent disease after fludarabine-based regimens with < 25% involvement by CLL/SLL cells
- •Patients with lymphoblastic lymphoma in remission or after partial response to chemotherapy
- •Patients with poor prognosis multiple myeloma by cytogenetics del13, del 17p, t(4;14) or t(14;16) or hypodiploidy, with advanced disease (stage >= 2) and /or relapsed after autologous stem cell transplant
- •Zubrod performance status 0-1 or Karnofsky performance status > 70%; patients > 50 years will have to have a Sorror Comorbidity Index =< 3
- •Available haploidentical donor willing and eligible to undergo a peripheral blood collection
- •Left ventricular ejection fraction (LVEF) > 40%
- •Bilirubin =< 1.5 mg/dl (unless Gilbert's syndrome), alanine aminotransferase (ALT) or aspartate aminotransferase (AST) =< 200 IU/ml for adults; conjugated (direct) bilirubin < 2 x upper limit of normal
- •Serum creatinine clearance >= 50 ml/min (calculated with Cockcroft-Gault formula)
- •Diffusing capacity for carbon monoxide (DLCO) >= 45% predicted corrected for hemoglobin
- •Patient or patient's legal representative must provide written informed consent
排除标准
- •Human immunodeficiency virus (HIV) positive; active hepatitis B or C
- •Patients with active infections; the principal investigator (PI) is the final arbiter of the eligibility
- •Liver cirrhosis with greater than grade 1 stage 1 inflammation/fibrosis
- •Uncontrolled central nervous system (CNS) involvement by tumor cells within the past 2 months
- •History of another primary malignancy that has not been in remission for at least 3 years; (the following are exempt from the 3-year limit: nonmelanoma skin cancer, fully excised melanoma in situ [stage 0], curatively treated localized prostate cancer, and cervical carcinoma in situ on biopsy or a squamous intraepithelial lesion on PAP smear)
- •Positive beta human chorionic gonadotropin (HCG) test in a woman with child bearing potential defined as not post-menopausal for 12 months or no previous surgical sterilization
- •Inability to comply with medical therapy or follow-up
研究组 & 干预措施
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Cyclophosphamide (Drug)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Filgrastim (Biological)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Fludarabine Phosphate (Drug)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Melphalan (Drug)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Peripheral Blood Stem Cell Transplantation (Procedure)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Rituximab (Biological)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Tacrolimus (Drug)
Treatment (peripheral blood stem cell transplantation)
Patients receive melphalan IV over 30 minutes on day -6 and fludarabine phosphate IV over 1 hour on days -6 to -3. Patients undergo TBI on day -2 and CD45RA depleted peripheral blood stem cell transplantation on day 0. Patients also receive cyclophosphamide IV over 3 hours on days 3-4. Beginning on day 5, patients receive tacrolimus IV for 2 weeks and PO for at least 4 months. Beginning on day 7, patients receive filgrastim SC daily. Patients with CD20 positive lymphoma may receive rituximab IV on days -13, -6, 1, and 8.
干预措施: Total-Body Irradiation (Radiation)
结局指标
主要结局
Incidence of treatment failure defined as primary graft failure, grade 3-4 acute graft versus host disease (aGVHD), or non-relapse mortality
时间窗: Up to 100 days
次要结局
- Immune reconstitution(Up to 3 years)
- Incidence of infectious episodes(Up to 3 years)
- Disease free survival (DFS) time(Up to 3 years)
- Overall survival (OS) time(Up to 3 years)