Post-Transplant Use of Irradiated Haplo-Allogeneic Cells
试验速览
- 阶段
- 早期 1 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 2
- 主要终点
- Number of Participants Who Received Irradiated Haploidentical Cells (IHC) With Disease Response
研究概览
简要总结
This pilot clinical trial studies the side effects of irradiated donor cells following stem cell transplant in controlling cancer in patients with hematologic malignancies. Transfusion of irradiated donor cells (immune cells) from relatives may cause the patient's cancer to decrease in size and may help control cancer in patients receiving a stem cell transplant.
详细描述
PRIMARY OBJECTIVES:
I. To determine the toxicity associated with the administration of irradiated haploidentical cells (IHC) to patients with high-risk hematologic malignancies.
SECONDARY OBJECTIVES:
I. To determine if there is evidence of disease response associated with IHC.
TERTIARY OBJECTIVES:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Patient with disease (stage) eligible per cohort
- •COHORT 1: patients undergoing high dose chemotherapy with autologous stem cell rescue and ?high-risk? disease as defined below:
- •Diffuse large cell lymphoma or peripheral T cell lymphoma (including specified World Health Organization [WHO] subtypes) not in computed tomography (CT)-positron emission tomography (PET) complete remission at time of high dose therapy
- •Diffuse large cell lymphoma with ?double hit? or ?double expressor? features
- •Diffuse large cell lymphoma or peripheral T cell lymphoma (including WHO specified subtypes) refractory to standard induction therapy OR relapsing within 1 year of treatment OR in greater that second complete remission (CR)
- •Mantle cell lymphoma not in CR1
- •Multiple myeloma with ONE (or more) of the following high risk features:
- •Less than very good partial remission at time of high dose therapy
- •High Revised-International Staging System (R-ISS) (stage III ? 2 microglobulin >= 5.5 plus lactate dehydrogenase [LDH] > upper limit of normal [ULN] and/or del17p, t(4;14), t(14;16)) at time of diagnosis
- •Cytogenetics or fluorescent in situ hybridization (FISH) del17p
- •COHORT 2: patients with high risk disease having undergone an allogeneic hematopoietic stem cell transplant from a 10/10 human leukocyte antigen (HLA) matched donor with one of the following disease subtypes:
- •Acute myeloid leukemia (AML) in CR1 with high risk features (European Leukemia Network [ELN]) at presentation
- •Diagnostic sample with either t(6;9), t(9;22), 11q23, inv 3, -5, -7, del17p, complex cytogenetics, NPMwt-flt3ITD+, OR p53 mutation (mut); patients whose samples have mutations in RUNX1 or ASXL1 are also eligible (unless the patient has favorable cytogenetics)
- •AML in CR1 with measurable minimal residual disease (MRD) by molecular (e.g., myeloid mutation profile, polymerase chain reaction [PCR] for NPM1, core-binding factor [CBF], mixed lineage leukemia [MLL]) or flow cytometry
- •AML not in CR1 (including patients with morphologic CR but with incomplete recovery, CRi)
- •Myelodysplastic syndrome (MDS) with complex cytogenetics, 17p deletion or p53 mutation, or JAK2 or RAS mutation
- •Treatment-related MDS or AML
- •Acute lymphoblastic leukemia (ALL) not in CR1
- •ALL with MRD
- •Any hematologic malignancy relapsed or with persistent disease after allogeneic hematopoietic stem cell transplant
- •Multiple myeloma
- •Non-Hodgkin lymphoma (NHL) with chemoresistant disease at time of transplant
- •Any patient undergoing allogeneic hematopoietic stem cell transplant and an anticipated rate of relapse > 80% based upon published data and for which there is consensus amongst the Hematologic Malignancies Tumor Study Group that enrollment is appropriate
- •Availability of a genetic child, genetic parent or sibling as a potential HLA haploidentical donor
- •Meets standard eligibility requirements for high dose chemotherapy with autologous stem cell rescue (COHORT 1) or allogeneic hematopoietic stem cell transplant (COHORT 2) and has signed consent for those procedures
- •DONOR: Donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched
- •DONOR: Donor must meet all Robert Wood Johnson (RWJ) Blood Services requirements for hematopoietic stem cell donation including:
- •Age >= 18 years old;
- •Normal hemogram (white blood cells [WBC] 4.0-10.0 x 10^3/mm^3; platelet count 150,000 to 440,000/mm^3 ; hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%
- •Not pregnant or lactating;
- •Not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-cell lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by RWJ Blood Services;
- •No uncontrolled infections, other medical or psychological/social conditions, or medications that might increase the likelihood of patient or donor adverse effects or poor outcomes;
- •Meet other blood bank criteria for blood product donation (as determined by RWJ Blood Center screening history and laboratory studies)
排除标准
- •Non-English speaking person
- •Patients undergoing haploidentical allogeneic hematopoietic stem cell transplants are not eligible; patients undergoing < 10/10 HLA allele matched allogeneic transplant are not eligible
- •Pregnant women
- •DONOR: Non-English speaking person
- •DONOR: Pregnant women
结局指标
主要结局
Number of Participants Who Received Irradiated Haploidentical Cells (IHC) With Disease Response
时间窗: Up to 8 weeks after last protocol treatment
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR + PR
the Number of Participants With Toxicities Associated With Administration of Irradiated Haploidentical Cells (IHC) Evaluated According to Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0
时间窗: Up to 12 weeks of completion of therapy
The anticipated/projected IHC-associated toxicities of greatest concern include: short-term toxicities- constitutional/systemic adverse events including fevers, hypotension, pulmonary infiltrates; long-term toxicities: autoimmune effects, graft-versus-host disease (GVHD), graft rejection. Toxicity will be measured by occurrence of any experimental treatment-related adverse events (AE) up to 12 weeks of completion of therapy. The CTCAE version 4.0 will be utilized for the description and grading of the AE. All symptoms, signs, or diseases assessed as experimental treatment-related will be captu
次要结局
- Induction of Host T Cells Reactive With Tumor Associated Epitopes(Up to 8 weeks after last protocol treatment)
研究者
Roger Strair, MD, PhD
Professor of Medicine, RWJMS
Rutgers Cancer Institute of New Jersey