Adoptive Transfer of Haploidentical NK Cells in Combination With Epratuzumab for the Treatment of Relapsed Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 2
- 试验地点
- 1
- 主要终点
- Time to Progression (TTP)
研究概览
简要总结
The goal of this clinical research study is to learn if transferring the donor's NK cells, in combination with an antibody called epratuzumab and low-dose interleukin (IL-2), into your body can be done safely. Researchers want to find out if the infused NK cells will survive after the infusion and if the NK cell infusion helps to destroy cancer cells in the recipient's body and possibly to help control the disease.
Primary Objectives:
· Evaluate the feasibility of collecting an adequate number of natural killer (NK) cells from a donor and evaluate the safety of a haploidentical donor-derived NK cell infusion, Epratuzumab, and low-dose interleukin-2 (IL-2).
Secondary Objectives:
- Quantification and persistence of the infused donor NK cell in vivo;
- Quantification and persistence of cytokine levels;
- Assessment of NK cell immunophenotype and function;
- Correlate above with anti-tumor effect.
详细描述
Study Drugs:
Epratuzumab is designed to attach to certain proteins on the surface of ALL cells. This may cause the cancer cells to die.
Cyclophosphamide is designed to interfere with the multiplication of cancer cells, which may slow or stop their growth. This may cause the cancer cells to die.
Fludarabine is designed to make cancer cells less able to repair damaged DNA (the genetic material of cells). This may increase the likelihood of the cells dying.
IL-2 is designed to help NK cells live longer and work better.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Recipient Inclusion criteria (within 28 days of this protocol's lymphodepleting conditioning regimen and after donor and recipient consent-signing)
- •Diagnosis of CD22+ acute lymphoblastic leukemia that is a. refractory to therapy or b. in second or greater relapse without other standard therapeutic options
- •Patient may have been the recipient of an allogeneic hematopoietic stem cell transplant; however; there must be no evidence of Graft-versus-host disease (GVHD)
- •Off prednisone or other immunosuppressive medications for at least 3 days prior to both the lymphodepleting regimen and the NK infusion
- •Zubrod performance scale </= 2 or Lansky performance scale >/= 60
- •Adequate renal function defined as: Serum creatinine (Cr), for adults </= 2 mg/dL, for children </= 2 mg/dL or </= 2 times upper limit of normal (ULN) for age (whichever is less). If abnormal renal function, then Cr clearance >/= 60 mL/min/1.73 m^2
- •Adequate liver function defined as: Total bilirubin </= 2 mg/dL and serum glutamic-pyruvic transaminase (SGPT)/ alanine transaminase(ALT) </= 5 * ULN for age (unless Gilbert's disease or abnormal liver function due to primary disease)
- •Pulmonary symptoms controlled by medication and pulse oximetry >/= 92% room air
- •Negative serum test to rule out pregnancy within 2 weeks prior to registration in females of childbearing potential (non childbearing is defined as greater than one year post-menopausal or surgically sterilized
- •Requirement of sexually active females and males to use any form of contraception considered effective and medically acceptable by the Investigator. [Acceptable forms: birth control implants, birth control pills, a vasectomy (male surgical sterilization), or a double-barrier method (any 2 of the following in combination: intrauterine device (IUD), male or female condom with spermicidal gel, a diaphragm, a sponge, and/or cervical cap)]
- •Negative serology for human immunodeficiency virus (HIV)
- •Donor must be related to recipient and is predicted to be alloreactive based upon the presence of the relevant KIR genes and incompatibility with the recipient for HLA C or Bw antigens
- •Donor must have infectious disease marker testing [Hepatitis B, C, HIV, CMV, Syphilis (RPR), Chagas, HTLV, and West Nile Virus] and CBC differential and platelet studies that meet standard medical eligibility criteria for allogeneic blood stem cell donation within 7 days of apheresis
- •Donor, if a female of childbearing potential (non-childbearing is defined as greater than one year post-menopause or surgically sterilized), must have a negative serum test to rule out pregnancy within 14 days of apheresis
- •Donor must meet standard medical eligibility criteria for allogeneic stem cell donation
排除标准
- •Exclusion criteria applies to both the initiation of conditioning regimen and to the NK infusion
- •Active central nervous system (CNS) leukemia
- •Active infection (defined as on antimicrobial therapy and or febrile)
- •Breast-feeding females
- •Currently using a ventilator or requiring supplemental oxygen
- •Currently undergoing dialysis
- •Currently using a Phase I, II, or III investigational agent. These agents should be stopped within 21 days of NK infusion
- •New detected cardiac arrhythmia not controlled with medical management within prior 72 hour period.
- •Hypotension requiring pressor support within prior 72 hour period
- •Uncontrolled infection defined as daily fever greater than or equal to 38.2°C within prior 24 hours and new positive culture for bacteria, fungus, or virus within 72 hours prior to NK -cell infusion, if clinically indicated
- •Taking corticosteroids by mouth or intravenously within prior 72 hour period
- •Ascites requiring paracentesis within prior 72 hour period. (If the patient requires paracentesis within 72 hours of NK cell infusion, they will not be eligible to receive the infusion.)
- •Seizure activity or clinically detectable encephalopathy or new focal neurologic deficits within prior 72 hour period
- •Donor has active infection (defined as on antimicrobial therapy and/or febrile) within 7 days of apheresis
- •Donor is pregnant female or breast-feeding female (within 7 days of apheresis)
研究组 & 干预措施
Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
干预措施: Epratuzumab (Drug)
Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
干预措施: Fludarabine (Drug)
Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
干预措施: Cyclophosphamide (Drug)
Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
干预措施: Mesna (Drug)
Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
干预措施: Infusion of NK cells (Procedure)
Haploidentical NK cells + Epratuzumab
Haploidentical donor-derived NK cell infusion, Epratuzumab 360 mg/m^2 once a day by vein (IV) on Day -4, Day -1 and Days 3, 6, 10, 13 and 17, and low-dose interleukin-2 (IL-2) Subcutaneous injections three times a week for 9 doses on Days 0 to 21; Fludarabine 25 mg/m^2 once a day IV on Day -6 through Day -2 over 30 minutes; Cyclophosphamide 60 mg/kg once a day IV on Days -5 and -4 over 2 hours. Mesna 12 mg/kg by vein 5 times per day on Days -5 and -4 over 15 minutes.
干预措施: Interleukin-2 (Drug)
结局指标
主要结局
Time to Progression (TTP)
时间窗: 1 Year
TTP calculated as average time, in months, from baseline to participants disease progression or death, monitored for a minimum of 1 year
次要结局
- Overall Survival (OS)(Minimum of 1 year, or until disease progression or death)