NCT01475058已完成1 期
A Phase I/II Study of Cellular Immunotherapy With Donor Central Memory-derived Virus-specific CD8+ T-cells Engineered to Target CD19 for CD19+ Malignancies After Allogeneic Hematopoietic Stem Cell Transplant
适应症
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 1
- 试验地点
- 2
- 主要终点
- Feasibility assessment of study treatment
研究概览
简要总结
This phase I/II trial studies the safety and toxicity of post-transplant treatment with donor T cells engineered to express a chimeric antigen receptor (CAR) targeting CD19 in patients who have had a matched related allogeneic hematopoietic stem cell transplant for a CD19+ B cell malignancy.
详细描述
PRIMARY OBJECTIVES:
I. To assess the safety and feasibility of pre-emptive adoptive T cell therapy using ex vivo expanded cytomegalovirus (CMV)- or Epstein-Barr virus (EBV)-specific T cells derived from donor CD62L+ central memory (TCM) cells and genetically modified to express a CD19-specific chimeric antigen receptor (CAR) in patients in complete remission after human leukocyte antigen (HLA)-matched related donor hematopoietic stem cell transplantation (HCT) for CD19+ B cell malignancies at high risk of post-HCT relapse. (Cohort A)
II. To assess the safety and feasibility of adoptive T cell therapy using ex vivo expanded CMV- or EBV-specific T cells derived from donor CD62L+ TCM cells and genetically modified to express a CD19-specific CAR in patients with persistent, progressive or relapsed disease after HLA-matched related donor HCT for CD19+ B cell malignancies. (Cohort B)
SECONDARY OBJECTIVES:
I. To determine the duration of in vivo persistence of adoptively transferred bi-specific CD8+ T cells, and the phenotype of persisting T cells.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with CD19+ B cell malignancy who have persistent, relapsed or progressive disease after hematopoietic stem cell transplant from an human leukocyte antigen (HLA)-matched related donor OR patients with CD19+ B cell malignancy who are planned for or have had a hematopoietic stem cell transplant from an HLA-matched related donor and are at risk of relapse after HCT defined by any one of the disease-specific criteria listed below:
- •Philadelphia chromosome negative acute lymphoblastic leukemia:
- •Beyond first complete remission (CR) at the time of pre-transplant evaluation
- •Required > 1 cycle of induction chemotherapy to achieve CR
- •First morphologic CR but with evidence of minimal residual disease by flow cytometry, conventional cytogenetics, fluorescence in situ hybridization (FISH) or polymerase chain reaction (PCR)
- •First CR with poor risk cytogenetics (t(4:11), t(8;14), hypodiploidy, near triploidy or > 5 cytogenetic abnormalities) at diagnosis
- •Planned for or have had a reduced intensity conditioned or non-myeloablative transplant
- •Philadelphia positive acute lymphoblastic leukemia
- •Not in CR at the time of pre-transplant evaluation
- •In CR with the following features:
- •Intolerant or unwilling to use a TKI after HCT
- •Current or previous detection of cytogenetic abnormalities in addition to t(9;22) by conventional karyotyping, FISH or molecular methods
- •Chronic lymphocytic leukemia, or low grade B cell lymphomas:
- •Failed or ineligible for prior immunochemotherapy that included a purine analog and anti-CD20 monoclonal antibody AND a lymph node >= 5 cm at the time of pre-transplant evaluation
- •Mantle cell lymphoma:
- •Failed or ineligible for autologous transplant AND a lymph node >= 2 cm at the time of pre-transplant evaluation
- •Diffuse large B cell lymphomas, large B cell transformation of an indolent lymphoma or other aggressive B cell lymphomas
- •Failed or ineligible for autologous transplant AND not in CR at the time of pre-transplant evaluation
- •Confirmation of tumor diagnosis and expression of CD19 after review by University of Washington Medical Center (UWMC) or Seattle Cancer Care Alliance (SCCA) pathology services
- •The patient has signed the informed consent form for this study
- •DONOR: Genotypic or phenotypic HLA-identical family members
- •DONOR: Express one or more of the following combinations of viral serostatus and HLA allele:
- •CMV seropositive and HLA-A*0101 positive
- •CMV seropositive and HLA-A*0201 positive
- •CMV seropositive and HLA-B*0702 positive
- •CMV seropositive and HLA-B*0801 positive
- •EBV seropositive and HLA-A*0201 positive
- •EBV seropositive and HLA-B*0801 positive
- •DONOR: Hematocrit >= 35% at enrollment
- •DONOR: Age >= 18 years
- •DONOR: The donor has signed the informed consent form for the study
排除标准
- •Known central nervous system (CNS) tumor (CNS2 or CNS3) that is refractory to intrathecal chemotherapy and/or cranio-spinal radiation; patients with a history of CNS disease that has been effectively treated to CNS1 or lower evidence of disease will be eligible
- •Human immunodeficiency virus (HIV) seropositive
- •Significant medical or psychological conditions that would make them unsuitable candidates for T cell therapy
- •Fertile patients unwilling to use contraception during and for 12 months after protocol enrollment
- •Pregnant or breast-feeding
- •DONOR: G-CSF administered within one month prior to the blood draw for T cell collection
- •DONOR: Unable for any reason to provide a 400 ml blood draw
- •DONOR: Inadequate peripheral veins for blood collection
- •DONOR: HIV-1, HIV-2, human T-lymphotropic virus (HTLV)-1 or HTLV-2 seropositive
- •DONOR: Active hepatitis B or hepatitis C virus infection
- •DONOR: Positive serologic test for syphilis
- •DONOR: Aberrant CD45RA isoform expression on all T cells
- •DONOR: Systolic blood pressure (BP) < 80 or > 200
- •DONOR: Heart rate < 50 or > 120, if considered due to cardiac disease
- •DONOR: Oxygen (O2) saturation < 88% on room air
- •DONOR: Serum creatinine (Cr) > 3.0
- •DONOR: Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 4 x the upper limit of normal
- •DONOR: Unable to provide informed consent to participate
- •DONOR: Significant medical conditions (e.g. immunosuppressive therapy) that would make them unsuitable T cell donors
- •DONOR: Pregnant or nursing
结局指标
主要结局
Feasibility assessment of study treatment
时间窗: Up to 5 years
If the prescribed T cell dose is delivered in more than 50% of the patients, this approach will be considered feasible for further study to reduce relapse after allogeneic HCT.
Safety and toxicity assessment of study treatment
时间窗: Up to day 42 after the T cell infusion
Incidence of grade \>= 3 toxicity, as defined by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 occurring from the T cell infusion through day 42 after the T cell infusion. Analysis will be performed separately in patients in complete remission (cohort A) or with detectable disease (cohort B) at day 28 post-transplant (prior to the T cell infusion). Incidence of acute GVHD occurring from the T cell infusion through day 42 after the T cell infusion will be assessed.
次要结局
- Anti-tumor efficacy and duration of persistence, migration, and function of adoptively transferred bi-specific effector cells(Up to 15 years)
研究者
Cameron Turtle
Principal Investigator
Fred Hutchinson Cancer Center
研究点 (2)
Loading locations...
相似试验
终止
1 期
Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell TransplantRecurrent Adult Acute Myeloid LeukemiaRecurrent Childhood Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaTherapy-Related Acute Myeloid LeukemiaDonorHematopoietic Cell Transplant RecipientHLA-A*0201 Positive Cells PresentRecurrent Acute Myeloid LeukemiaNCT01640301Fred Hutchinson Cancer Center47
进行中（未招募）
1 期
Genetically Modified T-cell Immunotherapy in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia and Persistent/Recurrent Blastic Plasmacytoid Dendritic Cell NeoplasmAdult Acute Myeloid Leukemia in RemissionAcute Biphenotypic LeukemiaEarly Relapse of Acute Myeloid LeukemiaLate Relapse of Acute Myeloid LeukemiaRecurrent Adult Acute Myeloid LeukemiaSecondary Acute Myeloid LeukemiaBlastic Plasmacytoid Dendritic Cell NeoplasmInterleukin-3 Receptor Subunit Alpha PositiveRefractory Acute Myeloid LeukemiaUntreated Adult Acute Myeloid LeukemiaAdult Acute Lymphoblastic LeukemiaAcute Myeloid LeukemiaMinimal Residual DiseaseNCT02159495City of Hope Medical Center31
已完成
1 期
Vaccine Therapy in Treating Patients With Stage IV Breast CancerHER2-positive Breast CancerRecurrent Breast CancerStage IV Breast CancerMale Breast CancerNCT00791037University of Washington23
已完成
2 期
Donor T Cells After Donor Stem Cell Transplant in Treating Patients With Hematologic MalignanciesAccelerated Phase Chronic Myelogenous LeukemiaAdult Acute Myeloid Leukemia With 11q23 (MLL) AbnormalitiesAdult Acute Myeloid Leukemia With Del(5q)Adult Acute Myeloid Leukemia With Inv(16)(p13;q22)Adult Acute Myeloid Leukemia With t(15;17)(q22;q12)Adult Acute Myeloid Leukemia With t(16;16)(p13;q22)Adult Acute Myeloid Leukemia With t(8;21)(q22;q22)Adult Nasal Type Extranodal NK/T-cell LymphomaAngioimmunoblastic T-cell LymphomaBlastic Phase Chronic Myelogenous LeukemiaChildhood Burkitt LymphomaChildhood Chronic Myelogenous LeukemiaChildhood Diffuse Large Cell LymphomaAnaplastic Large Cell LymphomaChildhood Immunoblastic Large Cell LymphomaChildhood Myelodysplastic SyndromesChildhood Nasal Type Extranodal NK/T-cell LymphomaChronic Phase Chronic Myelogenous LeukemiaCutaneous B-cell Non-Hodgkin Lymphomade Novo Myelodysplastic SyndromesExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueHepatosplenic T-cell LymphomaIntraocular LymphomaNodal Marginal Zone B-cell LymphomaNoncutaneous Extranodal LymphomaPeripheral T-cell LymphomaPreviously Treated Myelodysplastic SyndromesRecurrent Adult Acute Lymphoblastic LeukemiaRecurrent Adult Acute Myeloid LeukemiaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Childhood Acute Lymphoblastic LeukemiaRecurrent Childhood Acute Myeloid LeukemiaRecurrent Childhood Anaplastic Large Cell LymphomaRecurrent Childhood Grade III Lymphomatoid GranulomatosisRecurrent Childhood Large Cell LymphomaRecurrent Childhood Lymphoblastic LymphomaRecurrent Childhood Small Noncleaved Cell LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaRecurrent/Refractory Childhood Hodgkin LymphomaRefractory Chronic Lymphocytic LeukemiaRefractory Hairy Cell LeukemiaRelapsing Chronic Myelogenous LeukemiaSecondary Myelodysplastic SyndromesSmall Intestine LymphomaSplenic Marginal Zone LymphomaT-cell Large Granular Lymphocyte LeukemiaTesticular LymphomaWaldenström MacroglobulinemiaPost-transplant Lymphoproliferative DisorderNCT01839916University of Chicago77
进行中（未招募）
1 期
Cellular Immunotherapy Following Chemotherapy in Treating Patients With Recurrent Non-Hodgkin Lymphomas, Chronic Lymphocytic Leukemia, or B-Cell Prolymphocytic LeukemiaB-Cell Lymphoma, Unclassifiable, With Features Intermediate Between Diffuse Large B-Cell Lymphoma and Classic Hodgkin LymphomaB-Cell Prolymphocytic LeukemiaHigh Grade B-Cell Lymphoma, Not Otherwise SpecifiedRecurrent Adult Burkitt LymphomaRecurrent Chronic Lymphocytic LeukemiaPost-Transplant Lymphoproliferative DisorderRecurrent Diffuse Large B-Cell LymphomaRecurrent Follicular LymphomaRecurrent Hairy Cell LeukemiaRecurrent Lymphoplasmacytic LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Small Lymphocytic LymphomaNCT02153580City of Hope Medical Center37