Pilot Study of Prophylactic Dose-Escalation Donor Lymphocyte Infusion After T Cell Depleted Allogeneic Stem Cell Transplant in High Risk Patients With Hematologic Malignancies
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 77
- 试验地点
- 1
- 主要终点
- Percentage of Patients Who Are Able to Receive at Least One DLI Treatment
研究概览
简要总结
This pilot phase II trial studies how well giving donor T cells after donor stem cell transplant works in treating patients with hematologic malignancies. In a donor stem cell transplant, the donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Giving an infusion of the donor's T cells (donor lymphocyte infusion) after the transplant may help increase this effect.
详细描述
PRIMARY OBJECTIVES:
I. To determine the feasibility of escalating dose regimen (EDR) donor lymphocyte infusion (DLI) as measured by the proportion of patients who receive at least one DLI.
SECONDARY OBJECTIVES:
I. To assess progression free survival (PFS) at 2 years after stem cell transplant (SCT) for high-risk hematologic malignancies receiving T-cell depleted grafts followed by escalating dose regimen (EDR) prophylactic DLI compared to historical controls not receiving DLI.
II. To assess the safety of EDR DLI for high-risk hematologic malignancies as measured by cumulative incidence of severe grade III-IV acute graft-versus-host disease (GVHD).
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
- 14 Years 至 75 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •INCLUSION CRITERIA PRIOR TO TRANSPLANT:
- •The clinical trial will be offered to all high risk (defined 3 below) patients with hematologic malignancies who require stem cell transplants as part of their standard of care using matched related or unrelated donors
- •Patients with high risk myeloid or lymphoid malignancies at stem cell transplant following American Society for Blood and Marrow Transplantation (ASBMT) criteria, including but not limited to conditions listed; these criteria apply BEFORE cyto-reductive therapy given within 28 days of planned conditioning:
- •Refractory acute myelogenous or lymphoid leukemia
- •Relapsed acute myelogenous or lymphoid leukemia
- •Myelodysplastic syndromes with 5% or more blasts
- •Chronic myelogenous leukemia in chronic phase 3 or more, blast phase presently, or second accelerated phase
- •Recurrent or refractory malignant lymphoma or Hodgkin's disease with less than a partial response at transplant
- •High risk chronic lymphocytic leukemia defined as no response or stable disease to the most recent treatment regimen
- •DONORS: Matched related or unrelated donor stem cell transplant (SCT) matched at human leukocyte antigen (HLA) A- B, C, and DRB1 by molecular methods; 7 of 8 matched donor acceptable for related donors
- •T-cell depletion with anti-thymocyte globulin (ATG) (rabbit or horse) or at least 30 mg of alemtuzumab total in the conditioning regimen
- •Immune suppression; planned post-transplant immune suppression should include tacrolimus or cyclosporin monotherapy (i.e., calcineurin inhibitor or CN) for alemtuzumab regimens and a second immune suppressant for ATG treated patients; other agents may be used if CN intolerance or toxicity occurs post-transplant
- •Zubrod performance status (PS) 0-2 or equivalent Karnofsky PS
- •Eligible for allogeneic transplant in the treating physicians' judgment and by institutional standards
- •ELIGIBILITY TO RECEIVE DLI POST-TRANSPLANT:
- •Donor lymphocytes available or able to be collected
- •No evidence of disease by standard morphology; minimal residual disease or molecular evidence of disease will not exclude
- •Absolute neutrophil count >= 500/μl
- •Platelet count >= 20,000/μl without transfusion for 7 days
- •Serum glutamic oxaloacetic transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) =< 5 x upper limit of normal (ULN)
- •Bilirubin =< 3 x ULN
- •No evidence of grade II or higher acute GVHD or chronic GVHD at initiation of first DLI
- •No systemic corticosteroids or immunosuppressive drugs (topical acceptable); replacement steroids for adrenal insufficiency are not excluded
排除标准
- •EXCLUSION CRITERIA PRIOR TO TRANSPLANT:
- •Pregnant or lactating females
- •Hepatitis B with positive viral load prior to transplant conditioning or hepatitis C virus
- •Human immune deficiency virus
- •Psychiatric illness that may make compliance to the clinical protocol unmanageable or may compromise the ability of the patient to give informed consent
- •Creatinine >= 2.0 mg/dL
- •SGOT and SGPT >= 5 x ULN; liver biopsy preferred for such patients
- •Bilirubin >= 3 x ULN (unless Gilbert's syndrome)
- •Diffusing capacity of the lung for carbon monoxide (DLCO) < 50% corrected for hemoglobin
- •Left ventricular ejection fraction or shortening fraction < 40%
- •Unlikely to be able to procure additional donor lymphocytes
研究组 & 干预措施
Treatment (DLI)
Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
干预措施: laboratory biomarker analysis (Other)
Treatment (DLI)
Patients receive DLI IV. Treatment repeats every 4-8 weeks for 5 doses in the absence of disease progression or unacceptable toxicity.
干预措施: therapeutic allogeneic lymphocytes (Biological)
结局指标
主要结局
Percentage of Patients Who Are Able to Receive at Least One DLI Treatment
时间窗: Up to 2 years
次要结局
- Treatment-related Mortality(At 2 year)
- Overall Survival (OS)(At 2 years)
- Rate of Acute GVHD (aGVHD) With Any Grade(At 1 year and 2 year)
- Rate of Chronic GVHD (cGVHD)(At 1 year and 2 year)
- Progression Free Survival (PFS)(2 years)