AML Therapy With Irradiated Allogeneic Cells
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Response Rate, Determined by Allogeneic Cell Therapy-related Mortality
研究概览
简要总结
This pilot clinical trial studies if cells donated by a close genetic relative can help maintain acute myeloid leukemia (AML) complete remission (CR). Eligible patients will receive a standard induction chemotherapy. If a complete remission results they will receive irradiated allogeneic cells from a HLA haploidentical relative. Only patients who obtain a CR after the standard induction chemotherapy are eligible for the experimental therapy (irradiated haploidentical cells).
详细描述
PRIMARY OBJECTIVES:
I. Toxicity of haploidentical allogeneic cellular therapy in patients in complete remission (CR) (or CR with incomplete platelet recovery [CRp]) after induction chemotherapy with fludarabine (fludarabine phosphate)-cytarabine.
II. Efficacy of haploidentical allogeneic cellular therapy in patients in CR (or CRp) after induction chemotherapy with fludarabine-cytarabine (remission rates at 6, 12, 18, 24 months).
SECONDARY OBJECTIVES:
I. Immunologic parameters before and after haploidentical therapy: host anti-leukemia T cells; host regulatory 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically proven non-M3 AML:
- •Refractory/relapsed AML OR
- •Initial diagnosis of AML in patient >= 60 years old
- •Total bilirubin =< 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)
- •Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional ULN
- •Cardiac left ventricular ejection fraction (LVEF) >= 35%
- •Serum creatinine =< 1.5 mg/dl
- •Any organ dysfunction thought to be secondary to disease will be considered separately and the patient will be included at the investigators discretion
- •Patients must give informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status =< 3
- •Must have a potential haploidentical donor (parent, sibling, child)
- •A patient is eligible for second enrollment (allo-cellular therapy) if all of the following inclusion criteria are met:
- •Patient must have documented CR or CRp after 1 or 2 cycles of fludarabine + cytarabine
- •Patient must not be a candidate for an allo-hematopoietic stem cell transplant (HSCT)
- •Patient must have a partially (>= 3/6 class I antigen) human leukocyte antigen (HLA)-matched (by serology or low resolution deoxyribonucleic acid [DNA] testing) relative able to serve as a donor
- •Patients must not have active uncontrolled infections, other medical or psychological/social conditions that might increase the likelihood of patient adverse effects or poor outcomes
- •Total bilirubin < 1.5 times upper limit of normal (ULN) institutional limits (unless Gilbert's disease)
- •AST(SGOT)/ALT(SGPT) =< 2.5 X institutional ULN
- •Serum creatinine < 2.0 mg/dl
- •ECOG performance status =< 2
- •DONOR: donor must be related to patient and be partially (>= 3/6 antigen) HLA-matched
- •DONOR: donor must meet all New Brunswick Affiliated Hospitals (NBAH) requirements for hematopoietic stem cell donation, including:
- •DONOR: age >= 18 years old
- •DONOR: white blood cells (WBC) 4.0-10.0 x 10^3/mm^3
- •DONOR: platelet count 150,000 to 440,000/mm^3
- •DONOR: hemoglobin/hematocrit; 12.5-18 g/dl, 38 to 54%
- •DONOR: not pregnant or lactating
- •DONOR: not human immunodeficiency virus (HIV)-1, HIV-2, hepatitis C virus (HCV), hepatitis B core or human T-lymphotropic virus (HTLV)-I/II seropositive; hepatitis B surface antigen (HB S ag) (-); meet other infectious disease screening criteria utilized by NBAH Blood Center
- •DONOR: 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
- •DONOR: meet other blood bank criteria for blood product donation (as determined by NBAH Blood Center screening history and laboratory studies)
排除标准
- •History of current or prior medical problems that the investigator feels will prevent administration of therapy or assessment of response due to excess toxicity
- •Patients with known active central nervous system (CNS) leukemia will be excluded from this clinical study
- •Known HIV-positive patients are excluded from the study
- •Patients may not be pregnant or breast feeding
研究组 & 干预措施
Standard chemotherapy followed by allogenic therapy
INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: fludarabine phosphate (Drug)
Standard chemotherapy followed by allogenic therapy
INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: cytarabine (Drug)
Standard chemotherapy followed by allogenic therapy
INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: donor lymphocytes (Biological)
Standard chemotherapy followed by allogenic therapy
INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Standard chemotherapy followed by allogenic therapy
INDUCTION CHEMOTHERAPY: Patients receive standard induction chemotherapy with fludarabine phosphate IV over 1 hour QD for 5 days and cytarabine IV over 4 hours for 5 days. G-CSF 5 mcg/kg will be started at day14 if day14 bone marrow does not have >5% leukemic blasts. Treatment may continue for 1 or 2 courses at the discretion of the treating physician. If the patient enters a complete remission they are eligible for ALLOGENEIC CELLULAR THERAPY: Patients eligible for the experimental therapy undergo irradiated Donor Lymphocyte Infusion (DLI) of 3 x 10^8 CD3+ cells/kg at 8 weeks. Patients with stable disease may repeat irradiated DLI every 8-12 weeks in the absence of disease progression or unacceptable toxicity.
干预措施: G-CSF (Drug)
结局指标
主要结局
Response Rate, Determined by Allogeneic Cell Therapy-related Mortality
时间窗: Up to 2 years
Patients' response rate will be determined by allogeneic cell therapy-related mortality. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study for failure to reach complete remission. Hence no outcomes are available.
Adverse Events Related to Experimental Therapy
时间窗: Up to 2 years
Patients will be observed for incidence of adverse events related to experimental therapy, graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0. Of the 6 patients enrolled, all were ineligible to enter the experimental treatment phase of the study because of failure to reach complete remission. None of the enrolled patients received experimental therapy (allogeneic donor lymphocyte therapy). The one death occurred while receiving standard therapy prior to eligibility for experimental allogeneic therapy. The remained of patients were ineligible for experimental therapy because they did not obtain a complete remission after standard induction chemotherapy.
Response Rate, Determined by Duration of Complete Remission
时间窗: Up to 2 years
Patients will be scored as being in continuous remission at 2 years or having relapsed sooner. Of the 6 patients enrolled, all were ineligible to enter the treatment phase of the study for failure to reach complete remission for allogenic treatment.
次要结局
- Progression Free Survival Probability for CR(At 2 years)
研究者
Roger Strair, MD, PhD
Professor of Medicine, RWJMS
Rutgers Cancer Institute of New Jersey