A Pilot Study of Myeloablative Allogeneic or Haploidentical Stem Cell Transplantation With High Dose PT-Cy in Relapsed/Refractory AML
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Event Free Survival (EFS) rate
研究概览
简要总结
The purpose of this research study is to look at overall health status and how acute myeloid leukemia (AML) responds to a stem cell transplant when followed with cyclophosphamide. Some participants enrolling in this study may receive a transplant from a sibling, some may receive a transplant from a matched unrelated donor, and some may receive what is called a haploidentical transplant. A haploidentical stem cell transplant is a type of transplant that occurs when a person who needs a transplant cannot find a donor who exactly matches their tissue type (either among family members or through a matched unrelated donor). When no matched donor is available, half-matched related (haploidentical) donors may be used. Haploidentical donors are first degree relatives such as siblings, children, or parents.
People who undergo a stem cell transplant can experience complications such as rejection of the stem cell transplant or severe graft-versus-host disease (GVHD). GVHD occurs when some of the cells from the donor attack the recipient's tissues, resulting in mild, moderate, or even life-threatening side effects to the recipient's skin, stomach, intestines, and liver. However, recent research has shown that receiving cyclophosphamide after stem cell transplant can improve the outcomes of the transplant, and that is the purpose of this study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •AML without complete remission (CR/CRc/CRi) after at least 2 induction therapies OR
- •AML that has relapsed within 6 months after obtaining a CR OR
- •AML that has relapsed more than 6 months after obtaining a CR, and has treatment failure (TF) or progressive disease (PD) following at least 1 re-induction regimen OR
- •AML that has relapsed post Allogeneic transplantation
- •Active AML (bone marrow blasts ≥ 5% by morphology, staining, or flow) and/or presence of estramedullary disease
- •Available HLA-haploidentical donor that meets the following criteria:
- •Blood-related family member (sibling (full or half), offspring, or parent, cousin, niece or nephew, aunt or uncle, or grandparent)
- •At least 18 years of age
- •HLA-haploidentical donor/recipient match by at least low-resolution typing per institutional standards
- •In the investigator's opinion, is in general good health, and medically able to tolerate leukapheresis required for harvesting HSC
- •No active hepatitis
- •Negative for HTLV and HIV
- •Not pregnant
- •NOTE: there were HLA-matched sibling and HLA-matched unrelated donor cohorts, but those closed without completion of accrual with Amendment 11
- •Karnofsky performance status ≥ 50 %
- •Adequate organ function as defined below:
- •Total bilirubin ≤ 2.5 mg/dl (unless the patient has a history of Gilbert's syndrome)
- •AST(SGOT) and ALT(SGPT) ≤ 3.0 x IULN
- •Creatinine ≤ 2.0 x IULN OR estimated creatinine clearance ≥ 30 mL/min/1.73 m2 by Cockcroft-Gault Formula
- •Oxygen saturation ≥ 90% on room air
- •LVEF ≥ 40%
- •FEV1 and FVC ≥ 40% predicted, DLCOc ≥ 40% predicted. If DLCO is < 40%, patients will still be considered eligible if deemed safe after a pulmonary evaluation.
- •At least 18 years of age at the time of study registration
- •Able to understand and willing to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable)
排除标准
- •Circulating blast count ≥ 10,000/uL by morphology or flow cytometry (cytoreductive therapies including leukapheresis or hydroxyurea are allowed)
- •Known HIV or Active hepatitis B or C infection
- •Known hypersensitivity to one or more of the study agents
- •Currently receiving or has received any investigational drugs within the 14 days prior to the first dose of study drug (Day -7)
- •Currently receiving or has received any intensive chemotherapy within the 14 days prior to the first dose of study drug (Day -7) (hydrea or other non-intensive regimens such as decitabine may be used but must stop at least one day prior to the first dose of study drug)
- •Pregnant and/or breastfeeding
- •Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, unstable cardiac arrhythmias, or psychiatric illness/social situations that would limit compliance with study requirements.
研究组 & 干预措施
Treatment (preparative regimen, transplant, cyclophosphamide)
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan IV over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2.
OR
FLUDARABINE AND TBI BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily on days -3 to 0.
AND
DONOR CELL INFUSION: Patients undergo HLA-matched sibling stem cell transplant, HLA-matched unrelated, or HLA-haploidentical transplant on day 0.
AND
POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
干预措施: busulfan (Drug)
Treatment (preparative regimen, transplant, cyclophosphamide)
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan IV over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2.
OR
FLUDARABINE AND TBI BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily on days -3 to 0.
AND
DONOR CELL INFUSION: Patients undergo HLA-matched sibling stem cell transplant, HLA-matched unrelated, or HLA-haploidentical transplant on day 0.
AND
POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
干预措施: fludarabine phosphate (Drug)
Treatment (preparative regimen, transplant, cyclophosphamide)
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan IV over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2.
OR
FLUDARABINE AND TBI BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily on days -3 to 0.
AND
DONOR CELL INFUSION: Patients undergo HLA-matched sibling stem cell transplant, HLA-matched unrelated, or HLA-haploidentical transplant on day 0.
AND
POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
干预措施: total-body irradiation (TBI) (Radiation)
Treatment (preparative regimen, transplant, cyclophosphamide)
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan IV over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2.
OR
FLUDARABINE AND TBI BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily on days -3 to 0.
AND
DONOR CELL INFUSION: Patients undergo HLA-matched sibling stem cell transplant, HLA-matched unrelated, or HLA-haploidentical transplant on day 0.
AND
POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
干预措施: Stem cell transplant (Procedure)
Treatment (preparative regimen, transplant, cyclophosphamide)
BUSULFAN AND FLUDARABINE BASED PREPARATIVE REGIMEN: Patients receive busulfan IV over 3 hours on days -7 to -4, fludarabine phosphate IV over 30-60 minutes on days -6 to -2, and cyclophosphamide IV over 60 minutes on days -3 and -2.
OR
FLUDARABINE AND TBI BASED PREPARATIVE REGIMEN: Patients receive fludarabine phosphate IV over 30-60 minutes on days -6 to -4 and undergo TBI twice daily on days -3 to 0.
AND
DONOR CELL INFUSION: Patients undergo HLA-matched sibling stem cell transplant, HLA-matched unrelated, or HLA-haploidentical transplant on day 0.
AND
POST-TRANSPLANT CYCLOPHOSPHAMIDE: Patients receive cyclophosphamide IV over 90 minutes on days 3 and 4.
干预措施: cyclophosphamide (Drug)
CRS preventive regimen
The final ~15 people enrolled who will be recipients of haploidentical transplants will receive tocilizumab IV over 60 minutes 6-12 hours prior to the start of the donor cell infusion.
干预措施: tocilizumab (Drug)
结局指标
主要结局
Event Free Survival (EFS) rate
时间窗: Assessed at 100 days post-transplant
The time from date of first dose of the preparative regimen until failure to engraft, treatment failure, disease progression/relapse, or death from any cause (whichever occurs first). Rates will be calculated with exact 95% confidence intervals.
次要结局
- Rate of Leukemia Free Survival (LFS)(Assessed at 100 days post-transplant)
- Transplant Related Mortality (TRM) Rate(Assessed at 100 days post-transplant)
- Rate of CRS with and without tocilizumab prophylaxis(Assessed up to day 7)
- Time to neutrophil engraftment(Assessed up to day 30)
- Incidence of chronic GVHD(1 year post-transplant starting at day +100)
- Time to platelet engraftment(Assessed up to day 100)
- Incidence of acute GVHD(Up to 100 days post-transplant)
- Overall Survival (OS)(Assessed at 1 year post-transplant)