Targeting Cross-presentation With Peginterferon Alfa-2a to Enhance Anti-leukemic Responses After Allogeneic Transplantation in High Risk Acute Myeloid Leukemia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 37
- 试验地点
- 1
- 主要终点
- Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α
研究概览
简要总结
This protocol is an open label, single arm, non-randomized, phase I / II clinical trial investigating the use of pegylated interferon alpha-2a (peg-IFN-α, Pegasys®, Genentech) for prevention of relapse in acute myeloid leukemia (AML) not in remission at the time of allogeneic hematopoietic stem cell transplantation (HCT).
详细描述
This protocol is an open label, single arm, non-randomized, phase I / II clinical trial investigating the use of pegylated interferon alpha-2a (peg-IFN-α, Pegasys®, Genentech) for prevention of relapse in acute myeloid leukemia (AML) not in remission at the time of allogeneic hematopoietic stem cell transplantation (HCT). The inability to attain remission status following induction therapy for AML remains a significant problem and is associated with poor outcomes. While HCT remains a curative option, its activity in the setting of relapsed or refractory AML is significantly diminished due to high relapse.
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 must have AML not in remission or at very high risk for HCT (Hematopoietic Cell Transplantation) relapse.
- •For newly diagnosed AML, patients must have achieved two consecutive induction attempts without achieving complete remission
- •For patients initially in complete remission whose AML relapses > 6 months after preceding remission, one re-induction must be attempted to be eligible
- •For AML patients with early relapse, in whom the preceding remission is shorter than 6 months duration, no re-induction regimen is necessary to be eligible
- •Patients with antecedent MDS (Myelodysplastic Syndrome) who progress to AML may have therapies rendered during both phases counted towards these requirements.
- •Patients with poor cytogenetic or molecular risk associated with very high risk for relapse after HCT may proceed without provisions for prior treatment. However, they must have received at least one induction attempt.
- •Patients must be ≥ 18 years of age and considered a candidate for HCT
- •Karnofsky ≥ 70% (Karnofsky performance status is measure of a cancer patients general well being and activities of daily life. Scores range from 100 to 0 where 100 is perfect health and 0 is death
- •Patients must meet acceptable organ function criteria: Total Bilirubin ≤2.5 mg%; AST (Aspartate transaminase) and ALT (Alanine transaminase) <5.0 X institutional upper limit of normal; GFR (Glomerular filtration rate) >40 mL/min/1.73 m2 for patients with creatinine levels above institutional normal; Lung function tests (DLCO, FEV1, FVC) > 50%; Ejection fraction > 50%
- •All patients must sign an informed consent
- •Women and men of child-bearing potential must agree to use adequate contraception
排除标准
- •Prior chemotherapy treatment for AML within 21 days from the initiation of HCT conditioning
- •Patients may NOT have evidence or symptoms of CNS disease at the time of enrollment
- •HIV or HTLV1 / HTLV2 (Human T-lymphotrophic virus) (seropositivity and/or PCR positivity)
- •Patients less than 18 years of age
- •Pregnant and nursing mothers are excluded from this study
- •Patients with untreated or uncontrolled neuropsychiatric illness
- •Any physical or psychological condition that, in the opinion of the investigator, would pose unacceptable risk to the patient
- •Uncontrolled infections
研究组 & 干预措施
peg-IFN-α
peg-IFN-α will be administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It will be administered by subcutaneous injection every 14 days beginning with dose level 1.
Dose Level -1 - 45mcg Dose Level 1 - 90mcg Dose Level 2 - 180 mcg
干预措施: peg-IFN-α (Drug)
peg-IFN-α
peg-IFN-α will be administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It will be administered by subcutaneous injection every 14 days beginning with dose level 1.
Dose Level -1 - 45mcg Dose Level 1 - 90mcg Dose Level 2 - 180 mcg
干预措施: Hematopoietic Cell Transplant (HCT) (Procedure)
peg-IFN-α
peg-IFN-α will be administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It will be administered by subcutaneous injection every 14 days beginning with dose level 1.
Dose Level -1 - 45mcg Dose Level 1 - 90mcg Dose Level 2 - 180 mcg
干预措施: Tacrolimus (Drug)
peg-IFN-α
peg-IFN-α will be administered prior to HCT (Hematopoietic Cell Transplant) and at three subsequent time points post HCT. (Maximum of 4 doses) It will be administered by subcutaneous injection every 14 days beginning with dose level 1.
Dose Level -1 - 45mcg Dose Level 1 - 90mcg Dose Level 2 - 180 mcg
干预措施: Methotrexate (Drug)
结局指标
主要结局
Phase 1: Maximum Tolerated Dose (MTD) of Peg-IFN-α
时间窗: Up to day 56 post-transplant or up to 14 days after final treatment with peg-IFN-α, whichever comes later. Data was collected up to 63 days.
The dose level assigned to the most participants is selected as the MTD. Participants from the arms for dose level 1 (90mcg, 3 participants) and dose level 2 (180mcg, 33 participants) were analyzed together to determine the MTD. Dosage levels are determined by dose-limiting toxicities (DLTs). Only DLTs encountered during the treatment period, prior to day 56 post HCT (or 14 days after final treatment, whichever comes later), are counted. DLTs after the treatment period are counted only if they reflect an ongoing toxicity that initiated in the treatment period.
Phase 2: Number of Patients That Relapse
时间窗: 6 Months Post HCT
The cumulative incidence of relapse, estimated using proportional hazard model for the competing risk of non-relapse mortality (NRM).
次要结局
- Phase 2: Overall Survival Time(1 year or until study stops, whichever is later. Median time of follow-up was 25 months.)
- Phase 2: Event Free Survival Time(1 year or until study stops, whichever is later. Median time of follow-up was 25 months.)
- Acute GVHD(6 months)
- Non-Relapse Mortality(1 year or until study stops, whichever is later. Median time of follow-up was 25 months.)