Phase II Trial of Allogeneic Hematopoietic Cell Transplantation for Peripheral T Cell Lymphoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 入组人数
- 91
- 试验地点
- 2
- 主要终点
- Progression-free survival (PFS) of HCT recipients on the RIC arm and the mRIC arm
研究概览
简要总结
Background:
Lymphoma is a type of blood cancer. Blood cell transplant can cure some people with lymphoma. Researchers want to see if they can limit the complications transplant can cause.
Objective:
To test if a stem cell transplant can cure or control lymphoma. Also to test if new ways of getting a recipient ready for a transplant may result in fewer problems and side effects.
Eligibility:
Recipients: People ages 12 and older with peripheral T cell lymphoma that does not respond to standard treatments
Donors: Healthy people ages 18 and older whose relative has lymphoma
Design:
Participants will be screened with:
Physical exam
Blood and urine tests
Bone marrow biopsy: A needle inserted into the participant s hip bone will remove marrow.
Donors will also be screened with:
X-rays
Recipients will also be screened with:
Lying in scanners that take pictures of the body
Tumor sample
Donors may donate blood. They will take daily shots for 5 7 days. They will have apheresis: A machine will take blood from one arm and take out their stem cells. The blood will be returned into the other arm.
Recipients will be hospitalized at least 2 weeks before transplant. They will get a catheter: A plastic tube will be inserted into a vein in the neck or upper chest. They will get antibody therapy or chemotherapy.
Recipients will get the transplant through their catheter.
Recipients will stay in the hospital several weeks after transplant. They will get blood transfusions. They will take drugs including chemotherapy for about 2 months.
Recipients will have visits 6, 12, 18, 24 months after transplant, then once a year for 5 years.
详细描述
Background:
- Mature neoplasms of T and/or natural killer cells, collectively called peripheral T-cell lymphomas (PTCL), are often poorly responsive to chemotherapy and therefore associated with significant morbidity and mortality.
- Allogeneic hematopoietic cell transplantation (HCT) has the potential to cure PTCL but the optimal approach to HCT for these diseases requires ongoing investigation
Objectives:
- For subjects on the reduced-intensity conditioning (RIC/mRIC) arms, to estimate the progression-free survival
- For subjects on the immunosuppression-only conditioning (IOC) and ATL/RIC arms, because they are high risk patients, to preliminarily estimate the proportion who are progression free at one year.
Eligibility:
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 120 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •INCLUSION CRITERIA-RECIPIENT:
- •Age >=12 years
- •Diagnosis of PTCL, confirmed by NCI pathology review, that is relapsed or refractory to prior therapy, and/or PTCL where upfront allo HCT in first remission is reasonable (PIT score of intermediate-low risk or higher or supported by clinical practice guidelines)
- •-ALK-positive ALCL patients will only be eligible if relapsed or refractory
- •At least one potential 7-8/8 HLA-matched related (excluding an identical twin) or unrelated donor (at HLA-A, -B, -C, and DR), or an HLA-haploidentical related donor, based on initial low resolution unrelated donor search and/or at least one biologically-related family member who has at least a 25% chance of being at minimum an HLAhaploidentical match and is potentially suitable to donate based on reported family history. HLA typing of potential donors and/or mutation testing does not need to be completed for eligibility.
- •Adequate end-organ function, as measured by:
- •For RIC: Left ventricular ejection fraction (LVEF) >= 40% by 2D echocardiogram (ECHO) or MUGA, left ventricular shortening fraction >= 20% by ECHO, or LVEF >= 30% if the patient has radiologic evidence of aortic, renal, or coronary artery vasculitis. For IOC: LVEF >= 30% by 2D ECHO or MUGA.
- •Pulmonary function tests: DLco (corrected for hemoglobin) and FEV1 >= 40% of predicted for the RIC arm, and >= 30% predicted for the IOC arm; or in pediatric patients, if unable to perform pulmonary function tests, there should be no evidence of dyspnea at rest, no requirement for supplemental oxygen, and oxygen saturation >92% on room air.
- •Bilirubin <= 3.0 mg/dL (unless due to Gilbert's syndrome or hemolysis) for patients receiving RIC and bilirubin <= 5.0 mg/dL for patients receiving IOC (unless due to Gilbert s syndrome or hemolysis); ALT and AST <= 10 x ULN for patients receiving RIC or IOC. Patients who are above these bilirubin, ALT, or AST thresholds may be eligible for the RIC or IOC arm if evaluated by a hepatologist who deems the liver function test abnormalities to be potentially disease related, either because of direct involvement by PTCL, due to an associated process such as hemophagocytic lymphohistiocytosis, or as sequelae of prior chemotherapy that is thought to improve with time.
- •Estimated creatinine clearance of >= 50 mL/min/1.73 m^2, calculated using eGFR in the clinical lab for adults and the Schwartz formula for pediatrics.
- •Karnofsky (adults) or Lansky (children) performance status of >= 50% or ECOG performance status of 2 or less for the RIC arm and Karnofsky (adults) or Lansky (children) >= 30% or ECOG performance status of 3 or less for the IOC arm
- •Ability of subject or parent/guardian to understand and the willingness to sign a written informed consent document
- •Not pregnant or breastfeeding.
- •As therapeutic agents used in this trial may be harmful to a fetus, individuals of childbearing potential and individuals who can father children must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for at least one year post-allo HCT.
排除标准
- •RECIPIENT:
- •Patients who are receiving any other investigational agents, with the exception of virus-specific cytotoxic T-cells for the treatment of viral infection/reactivation prior to allo HCT.
- •Prohibitive allergy to a study drug or to compounds of similar chemical or biologic composition of the agents (e-ATG, steroids, cyclophosphamide, busulfan, pentostatin, sirolimus, MMF, filgrastim or biosimilar drug) used in the study
- •Lack of central venous access potential
- •Active psychiatric disorder which is deemed by the PI to have significant risk of compromising compliance with the transplant protocol or which does not allow for appropriate informed consent
- •INCLUSION CRITERIA-RELATED DONOR:
- •Related donor deemed suitable and eligible, and willing to donate, per clinical evaluations who are additionally willing to donate blood and/or peripheral blood stem cells for research. Related donors will be evaluated in accordance with existing Standard Policies and Procedures for determination of eligibility and suitability for clinical donation.
- •EXCLUSION CRITERIA-RELATED DONOR:
- •INCLUSION CRITERIA (UNRELATED DONOR):
- •Unrelated donors will be evaluated in accordance with existing NMDP Standard Policies and Procedures, available at: http://bethematch.org/About-Us/Global-transplantnetwork/ Standards/, except for the additional requirement of EBV serostatus testing for clinical purposes of donor selection. Note that participation in this study is offered to all unrelated donors but not required for clinical donation, so it is possible that not all unrelated donors will enroll on this study. Unrelated donors only enroll if they contribute research specimens, which is optional.
- •EXCLUSION CRITERIA (UNRELATED DONOR):
- •Unrelated donors: failure to qualify as a National Marrow Donor Program (NMDP) donor per current NMDP Standards, available at: http://bethematch.org/About-Us/Globaltransplant- network/Standards/. Exceptions to donor eligibility (e.g. foreign travel, tattoos) do not automatically exclude the donor and will be reviewed by the PI.
研究组 & 干预措施
2/IOC Arm
Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis
干预措施: GVHD prophylaxis (Drug)
5/ATL-RIC Arm
modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis
干预措施: GVHD prophylaxis (Drug)
5/ATL-RIC Arm
modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis
干预措施: ATL-RIC (Drug)
4/mRIC Arm
modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
干预措施: mRIC (Drug)
2/IOC Arm
Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis
干预措施: allo HCT (Procedure)
1/RIC Arm
Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
干预措施: GVHD prophylaxis (Drug)
2/IOC Arm
Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis
干预措施: IOC (Drug)
1/RIC Arm
Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
干预措施: RIC (Drug)
4/mRIC Arm
modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
干预措施: allo HCT (Procedure)
1/RIC Arm
Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
干预措施: allo HCT (Procedure)
3/Donor Arm
Donors for Recipients in Arm 1, Arm 2, Arm 4, or Arm 5
4/mRIC Arm
modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis
干预措施: GVHD prophylaxis (Drug)
5/ATL-RIC Arm
modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis
干预措施: allo HCT (Procedure)
结局指标
主要结局
Progression-free survival (PFS) of HCT recipients on the RIC arm and the mRIC arm
时间窗: 1 year post transplant
Number of patients who are alive and with PFS at one year, assessed by Kaplan-Meier with 80% and 95% two-sided confidence intervals
Progression-free survival (PFS) of HCT recipients on the IOC arm and ATL-RIC arm
时间窗: 1 year post transplant
Number of patients who are alive and with PFS at one year, assessed by Kaplan-Meier with 80% and 95% two-sided confidence intervals
次要结局
- secondary graft failure(1 year post transplant)
- kinetics and durability of lineage-specific donor chimerism(days +21, +28, +35, +42, and + 60 post transplant)
- Incidence of Acute Graft versus-host disease(1 year post transplant)
- event-free survival(1, 3, and 5 years post transplant)
- overall survival(1, 3, and 5 years post transplant)
- incidence of EBV, CMV, JCV, BKV, adenovirus, and HHV6(day +100 post transplant)
- GVHD-free relapse-free survival (GRFS)(1, 3, and 5 years post transplant)
- primary graft failure(60 days post transplant)
- lymphoma relapse(1, 3, and 5 years post transplant)
- kinetics and durability of engraftment(days +28, +42, +60, +100, +180, and 1 year post transplant)
- GVHD-free graft failure-free survival (GGFS)(1, 3, and 5 years post transplant)
- Incidence of Chronic Graft versus-host disease(1 and 2 years post transplant)
- transplant-related mortality(180 days and 1 year post transplant)
- disease-free survival(1, 3, and 5 years post transplant)