Pilot Study of Total Marrow/Lymphoid Irradiation (TMLI) Conditioning Prior to Allogeneic Hematopoietic Stem Cell Transplant (HCT) Followed by Post Transplant Cyclophosphamide-Based Graft Versus Host Disease Prophylaxis for Acute Myelogenous Leukemia in Complete Remission
试验速览
- 阶段
- 1 期
- 状态
- 暂停
- 发起方
- 入组人数
- 56
- 试验地点
- 1
- 主要终点
- 1b. Incidence of adverse events
研究概览
简要总结
This pilot phase I trial studies the side effects of total bone marrow and lymphoid irradiation and how well it works with cyclophosphamide in treating patients with acute myeloid leukemia. Total marrow and lymphoid irradiation targets cancer in bone marrow and blood, instead of applying radiation to the whole body. Giving total bone marrow and lymphoid irradiation before a donor transplant helps stop the growth of cells in the bone marrow, including normal blood-forming cells (stem cells) and cancer cells. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving total bone marrow and lymphoid irradiation before donor transplant and cyclophosphamide after transplant may work better at treating acute myeloid leukemia.
详细描述
PRIMARY OBJECTIVE:
I. To evaluate the safety/feasibility of combining a total marrow and lymphoid irradiation (TMLI) transplant conditioning regimen with a post-transplant high dose cyclophosphamide (PTCy)-based graft versus host disease (GvHD) prophylaxis strategy, through the assessment of: adverse events: type, frequency, severity, attribution, time course, duration and complications: including acute GvHD, infection and delayed neutrophil/platelet engraftment.
SECONDARY OBJECTIVES:
I. To estimate the cumulative incidence (CI) of acute GvHD at 100 days post allogeneic hematopoietic cell transplantation (alloHCT).
II. To estimate the CI of chronic GvHD at 6 months, 1- and 2-years post alloHCT.
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
- 16 Years 至 60 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •This study is open to patients with acute myeloid leukemia (AML) evaluated within 30 days of the start of conditioning regimen and in first or second complete remission (CR)
- •Karnofsky performance status (KPS) >= 70%
- •The effects of radiation on the developing fetus are known to be teratogenic; for this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control or abstinence) prior to study entry and for six months following duration of study participation; should a woman become pregnant or suspect that she is pregnant while participating on the trial, she should inform her treating physician immediately
- •Patients with acute myelogenous leukemia (AML) who are in first or second complete remission
- •All candidates for this study must have a human leukocyte antigen (HLA) (A, B, C, DR) identical sibling who is willing to donate primed blood stem cells (preferred) or bone marrow, or have a 10/10 allele matched unrelated donor; all ABO blood group combinations of the donor/recipient are acceptable since even major ABO compatibilities can be dealt with by various techniques; (red cell exchange or plasma exchange)
- •A cardiac evaluation with an electrocardiogram showing no ischemic changes or abnormal rhythm and an ejection fraction of >= 50% established by multi-gated acquisition scan (MUGA) or echocardiogram
- •Patients must have a serum creatinine of less than or equal to 1.3 mg/dL or creatinine clearance > 70 ml/min as calculated by the Cockcroft-Gault formula
- •A bilirubin of less than or equal to 1.5 mg/dL, excluding patients with Gilbert's disease
- •Patients should also have a serum glutamic-oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) less than 5 times the upper limit of normal
- •Pulmonary function tests including diffusing capacity of the lung for carbon monoxide (DLCO) will be performed; forced expiratory volume in 1 second (FEV 1) and DLCO should be greater than 50% of predicted normal value
- •All subjects must have the ability to understand and the willingness to sign a written informed consent; signed informed consent form approved by the Institutional Review Board (IRB) is required; the patient, family member, and transplant staff physician (physician, nurse, and social worker) meet at least once prior to starting the transplant procedure; during this meeting, all pertinent information with respect to risks and benefits to the donor and recipient will be presented; alternative treatment modalities will be discussed
- •The time from the end of last induction, re-induction, or consolidation regimen should be greater than or equal to 14 days
- •Prior therapy with etoposide and cyclophosphamide is allowed
- •DONOR: donor evaluation and eligibility will be assessed as per current City of Hope standard operating procedure (SOP)
排除标准
- •Patients should not have any uncontrolled illness including ongoing or active or poorly controlled infection
- •Patients may not be receiving any other investigational agents, or concurrent biological, chemotherapy, or radiation therapy; maintenance therapy with Food and Drug Administration (FDA)-approved targeted therapies (e.g. tyrosine kinase inhibitors for Philadelphia chromosome [Ph] positive [+] acute lymphoblastic leukemia [ALL], and FLT inhibitors for FLT3+ patients) will be allowed after day 60 disease assessment
- •Prior radiation therapy that would exclude the use of TMLI
- •Relapsed patients who have undergone autologous or allogeneic hematopoietic stem cell transplantation previously
- •Patients with psychological or medical condition that patient's physician deems unacceptable to proceed to allogeneic hematopoietic stem cell transplantation
- •Electrocardiogram (EKG) showing ischemic changes or abnormal rhythm and/or an echocardiogram or MUGA scan showing abnormal wall motion or ejection fraction < 50%
- •Patients who have been treated with chemotherapy or radiation for the purpose of induction, re-induction or consolidation, within two weeks of planned study enrollment
- •Patients with other active malignancies are ineligible for this study, other than localized malignancies
- •Patients that are pregnant or breastfeeding
- •Any other condition that would, in the investigator's judgment, contraindicate the patient's participation in the clinical study due to safety concerns or compliance with clinical study procedures, including but not limited to, infection/inflammation, intestinal obstruction, unable to swallow medication, social/ psychological issues, etc.
- •Subjects, who in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study
研究组 & 干预措施
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Allogeneic Hematopoietic Stem Cell Transplantation (Procedure)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Cyclophosphamide (Drug)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Filgrastim (Biological)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Laboratory Biomarker Analysis (Other)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Quality-of-Life Assessment (Other)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Questionnaire Administration (Other)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Tacrolimus (Drug)
Treatment (TMLI, cyclophosphamide)
Patients undergo TMLI BID on days -4 to 0, then undergo bone marrow or peripheral blood stem cell transplant on day 0. Patients receive cyclophosphamide IV over 2 hours on days 3 and 4, tacrolimus given by CIV on days 5-90, and filgrastim beginning on day 5 until ANC is at least 1,500/mm^3 for 3 consecutive days.
干预措施: Total Marrow Irradiation (Radiation)
结局指标
主要结局
1b. Incidence of adverse events
时间窗: Up to 24 months
Assessed using National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 scale. Scale range: Grade 1-5 (increasing grade reflects increasing severity), where Grade 1 reflects a more milder form of the adverse event and Grade 5=death.
1a. Incidence of adverse events
时间窗: Up to 24 months
Assessed using Bearman Scale Regimen-Related Toxicity scale. Scale range: Grade 0-4 (increasing grade reflects increasing severity), where Grade 0-none/did not experience and Grade 4=death.
次要结局
- Time to neutrophil and platelet recovery/engraftment(From day 0 to recovery or declaration of engraftment failure, assessed up to 24 months)
- Relapse-free survival(From the start of treatment to the date of death, disease relapse, or last follow-up whichever occurs first, assessed up to 24 months)
- Quality of life-Function Assessment(Up to 24 months)
- Chronic GVHD(From day (80) 100 to the onset of chronic GvHD, death or last contact, whichever comes first, assessed up to 24 months)
- GvHD-free/relapse-free survival (GRFS)(From start of treatment (hematopoietic stem cell transplant [HCT]) to grade 3-4 acute GvHD, chronic GvHD requiring systemic treatment, relapse, or death (from any cause), whichever occurs first, assessed p to 24 months)
- Relapse(From start of therapy, assessed up to 24 months)
- Acute graft versus host disease (GvHD)(Day 0 to 100 (120) days post-transplant)
- Quality of life -Questionnaire(Up to 24 months)
- Overall survival(From start of treatment until death, or last follow-up, whichever comes first, assessed up to 24 months)
- Non-relapse mortality (NRM)(From start of treatment until non-disease related death, or last follow-up, whichever comes first, assessed up to 24 months)
- Bone marrow residual damage assessment(Up to 24 months)
- Cytokines(Up to 24 months)
- Oxidative stress Markers(Up to 24 months)
- Quality of life -Symptom Inventory(Up to 24 months)
- Levels of immune cells(Up to 24 months)