MT2007-12 Allogeneic Natural Killer Cells With Rituximab in Patients With CD20 Positive Relapsed Non-Hodgkin Lymphoma or Chronic Lymphocytic Leukemia. Strategies to Increase Sensitivity of CLL Tumor Cells to Natural Killer Cell-Immune-Mediated Cytolysis

Masonic Cancer Center, University of Minnesota1 个研究点分布在 1 个国家目标入组 6 人开始时间: 2008年1月最近更新: 2017年12月28日

适应症

干预措施

试验速览

阶段: 1 期
状态: 终止
发起方: Masonic Cancer Center, University of Minnesota
入组人数: 6
试验地点: 1
主要终点: Number of Patients Exhibiting Natural Killer Cell Expansion

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

RATIONALE: Aldesleukin may stimulate natural killer cells to kill cancer cells. Treating natural killer cells with aldesleukin in the laboratory may help the natural killer cells kill more cancer cells when they are put back in the body. Giving monoclonal antibodies, such as rituximab, and chemotherapy drugs, such as fludarabine and cyclophosphamide, before a donor natural killer cell infusion helps stop the growth of cancer cells. It also helps stop the patient's immune system from rejecting the donor's stem cells.

PURPOSE: This phase I/II trial is studying how well giving rituximab and chemotherapy followed by a donor natural killer cell infusion that has been treated in the laboratory with aldesleukin followed by aldesleukin works in treating patients with non-Hodgkin lymphoma or chronic lymphocytic leukemia.

详细描述

OBJECTIVES:

Primary

To determine if allogeneic natural killer (NK) cells infused following chemoimmunotherapy can be safely expanded in vivo with aldesleukin.

Secondary

To determine if interleukin-15 production at day 0 correlates with NK cells expansion.
To determine overall response rate at 3 months.
To determine time to progression and overall survival.
To characterize the quantitative and qualitative toxicities of this treatment plan.
To determine the incidence of donor products that do not meet release criteria and the NK cell numbers infused.
To correlate clinical response with donor/recipient KIR ligand matching status, FcG receptor 3A genotype, and NK cells phenotype and function
To determine pharmacodynamic and pharmacogenomic markers and correlate them with NK cell expansion and disease response.

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 —（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Patient 18 years or older with a diagnosis of non-Hodgkin Lymphoma or chronic lymphocytic leukemia (NHL or CLL) and one of the following:
•Progression of NHL following at least 2 prior chemotherapy regimens, (must contain rituximab for all NHL and fludarabine for follicular NHL) defined as:
•failure to achieve partial remission (PR) with the last chemotherapy
•disease progression within 6 months following last chemotherapy
•Progression of CLL/SLL (small lymphocytic lymphoma) following at least 2 prior chemotherapy regimens (containing purine analogs ) in stage Rai III or IV or symptomatic disease.
•Relapsed NHL or CLL following stem cell transplantation for whom the option of donor lymphocyte infusion is not available or clinically indicated (e.g. recipients of autologous or umbilical cord blood [UCB] transplants).
•Available related HLA-haploidentical (human leukocyte antigen) natural killer (NK) cell adult donor by at least Class I serologic typing
•Karnofsky performance status > 60%
•Measurable disease based on modified Response Evaluation Criteria In Solid Tumors (RECIST)
•Have acceptable organ function as defined within 28 days of enrollment:
•Hematologic: platelets ≥ 80,000 x 10^9/L; hemoglobin ≥ 9g/dL, unsupported by transfusions; absolute neutrophil count (ANC) ≥ 1000 x 10^9/L, unsupported by granulocyte-colony stimulating factor or granulocyte-macrophage colony-stimulating factor (G-CSF or GM-CS)F for 10 days or Neulasta for 21 days - the hematologic requirements are waived for patients with inadequate counts due to known bone marrow involvement by lymphoma who are otherwise eligible
•Renal: glomerular filtration rate (GFR) > 50 ml/min
•Hepatic: alanine aminotransferase (ALT), aspartate aminotransferase (AST) < 3 x upper limit of normal and total bilirubin <3 mg/dl
•Pulmonary function: >50% corrected carbon monoxide diffusing capacity (DLCO) and Forced Expiratory Volume in the first second (FEV1)
•Cardiac: no symptoms of uncontrolled cardiac disease, left ventricular ejection fraction >40%
•Off prednisone or other immunosuppressive medications for at least 3 days prior to Day 0
•Women of childbearing potential must agree to use adequate contraception (diaphragm, birth control pills, injections, intrauterine device [IUD], surgical sterilization, subcutaneous implants, or abstinence, etc.) for the duration of treatment.
•Voluntary written informed consent before performance of any study-related procedure not part of normal medical care.

排除标准

•Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. All females of childbearing potential must have a blood test or urine study within 2 weeks prior to registration to rule out pregnancy. Women of childbearing age must use appropriate contraceptive method.
•Active central nervous system (CNS) lymphoma/leukemia
•Active serious infection (pulmonary infiltrates or lesions are allowed only after the appropriate diagnostic testing is negative for infection or appropriate therapy was initiated for probable infection)
•Pleural effusion - large enough to be detectable on the chest x-ray
•Allergy to rituximab or IL-2
•Human immunodeficiency virus (HIV) and associated non-Hodgkins lymphoma (NHL)
•Active concurrent malignancy (except skin cancer) requiring systemic therapy in the past 2 years
•Epstein-Barr virus (EBV) post-transplant lymphoproliferative disorder
•Positive hepatitis B surface antigen (HBsAg). If Hepatitis B core antibody (HBcAb) is positive, Hepatitis B deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR) will be evaluated. Positive anti HBcAb and undetectable viral load does not exclude the patient.
•Any experimental therapy in the past 30 days
•Donor Selection:
•Related donors (sibling, parent, offspring, parent or offspring of an HLA identical sibling) ≥ age 18 years
•Able and willing to undergo lymphapheresis
•HLA-haploidentical donor/recipient match. If time permits and multiple donors are available, preference will be given to the Killer-cell Immunoglobulin-like Receptors (KIR) ligand mismatched donor (as predicted by HLA typing).
•HIV-1, HIV-2 negative, Human T-lymphotropic virus Type I (HTLV-1), HTLV-2 negative, West Nile virus (WNV) negative, Hepatitis B and C negative
•Adequate organ function defined as:
•Hematologic: CBC/diff/platelet count near normal limits,
•Hepatic: ALT < 2 x upper limit of normal,
•Not pregnant or lactating
•In general good health as determined by the study physician
•Able to give informed consent