Allogeneic Hematopoietic Cell Transplantation for Peripheral T Cell Lymphoma
- Conditions
- Peripheral T-cell LymphomasLymphoproliferative DisordersImmune System Diseases
- Interventions
- Registration Number
- NCT03922724
- Lead Sponsor
- National Cancer Institute (NCI)
- Brief Summary
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.
- Detailed Description
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:
* Patients age \>= 12 years
* PTCL that is relapsed or refractory to prior therapy and/or PTCL of a risk score where upfront allo HCT in first remission is reasonable (PIT score of intermediate-low risk or higher or supported by clinical practice guidelines1)
* At least one potentially suitable 7-8/8 HLA-matched related or unrelated donor (at HLA A, B, C, and DR), or an HLA-haploidentical related donor
* Adequate end-organ function
* Not pregnant or breastfeeding
Design:
* There will be four recipient treatment arms that vary in approach, although all with the same backbone of conditioning and GVHD prophylaxis:
* Immunosuppression-only conditioning (IOC) arm for high-risk subjects
* Reduced-intensity conditioning (RIC) arm for those deemed not high-risk and able to tolerate RIC and without adult T cell leukemia/lymphoma (ATL)
* mRIC arm for patients eligible for the RIC arm, as a modified expansion upon completion of the RIC arm
* ATL-RIC arm for patients with a diagnosis of ATL
* IOC arm: equine anti-thymocyte globulin (e-ATG) 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m2/day IV on days -9 and -5, low-dose cyclophosphamide (5 mg/kg) orally daily on days -9 through -2
--Subjects will be assigned to the IOC arm if there is significant end-organ dysfunction present and it is felt that a conditioning regimen that includes busulfan would likely be associated with intolerable or life-threatening toxicities for the patient. Patients will also be assigned to the IOC arm if they possess a DNA repair defect, telomere maintenance defect, or familial cancer predisposition syndrome that necessitates limiting chemotherapy as much as possible to prevent future cancer risk.
* RIC arm: e-ATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide (5 mg/kg) orally daily on days -11 through - 4; busulfan IV, pharmacokinetically dosed, on days -3 and -2.
* mRIC arm: e-ATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide (5 mg/kg) orally daily on days -11 through - 4; busulfan IV, pharmacokinetically dosed, on days -3 and -2, filgrastim or biosimilar drug 5 mcg/kg/day subcutaneous on days -12, -8, and -4.
* ATL-RIC arm: e-ATG 40 mg/kg/day IV on days -14 and -13, pentostatin 4 mg/m2/day IV on days -11 and -7, low-dose cyclophosphamide (5 mg/kg) orally daily on days -11 through -4; busulfan IV, pharmacokinetically dosed, on days -3 and -2, filgrastim or biosimilar drug 5 mcg/kg/day subcutaneous on days -12, -8, and -4, ruxolitinib 45 mg/day from day -12 through day -2, and zidovudine 300 mg orally three times a day from day -1 through day +50.
* Peripheral blood stem cells are the preferred graft source, although bone marrow is permitted
* GVHD prophylaxis: Post-transplantation cyclophosphamide (PTCy) on days +3 and +4 (50 mg/kg/day on RIC arm, mRIC, and ATL-RIC arms and 25 mg/kg/day on the IOC arm, with the option of 25 mg/kg/day on the RIC arm). Sirolimus on days +5 through +60 (RIC arm, mRIC arm, IOC arm). Patients with somatic mutations in the Akt/mTOR pathway may receive tacrolimus days +5 through +60 instead of sirolimus on the RIC, mRIC, or IOC arms. Mycophenolate mofetil (MMF) on days +5 through +25 on the RIC, IOC, and mRIC arms; MMF will not be given on the ATL-RIC arm. Patients on the ATL-RIC arm will receive tacrolimus on days +5 through +50 and ruxolitinib 15 mg/day from days +5 through +35, 10 mg/day from days +36 through +60, and 5 mg/day from days +61 through +70.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 330
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 4/mRIC Arm allo HCT modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis 4/mRIC Arm GVHD prophylaxis modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis 1/RIC Arm RIC Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis 1/RIC Arm GVHD prophylaxis Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis 5/ATL-RIC Arm GVHD prophylaxis modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis 4/mRIC Arm mRIC modified Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis 5/ATL-RIC Arm ATL-RIC modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis 1/RIC Arm allo HCT Reduced Intensity Conditioning Arm, plus allogeneic HCT with GVHD prophylaxis 2/IOC Arm GVHD prophylaxis Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis 2/IOC Arm allo HCT Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis 2/IOC Arm IOC Immunosuppression Only Conditioning, plus allogeneic HCT with GVHD prophylaxis 5/ATL-RIC Arm allo HCT modified Reduced Intensity Conditioning Arm for ATL patients, plus allogeneic HCT with GVHD prophylaxis
- Primary Outcome Measures
Name Time Method Progression-free survival (PFS) of HCT recipients on the RIC arm and the mRIC arm 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 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
- Secondary Outcome Measures
Name Time Method secondary graft failure 1 year post transplant Cumulative incidence of secondary graft failure at 1 year post transplant.
kinetics and durability of lineage-specific donor chimerism days +21, +28, +35, +42, and + 60 post transplant Association between early chimerism data and primary or secondary graft failure
Incidence of Acute Graft versus-host disease 1 year post transplant Cumulative incidence of acute graft versus host disease at 1 year post transplant
event-free survival 1, 3, and 5 years post transplant Time from transplant to death of any cause or other event, including disease relapse, graft failure
overall survival 1, 3, and 5 years post transplant Time from transplant to death of any cause
incidence of EBV, CMV, JCV, BKV, adenovirus, and HHV6 day +100 post transplant cumulative incidence of EBV, CMV, JCV, BKV, adenovirus, and HHV6 in blood
GVHD-free relapse-free survival (GRFS) 1, 3, and 5 years post transplant Time from transplant to death from any cause of other event
primary graft failure 60 days post transplant Cumulative incidence of secondary graft failure at 60 days post transplant.
lymphoma relapse 1, 3, and 5 years post transplant Time from transplant to disease relapse
kinetics and durability of engraftment days +28, +42, +60, +100, +180, and 1 year post transplant The percentage of donor T-, B-, NK-, and myeloid cell populations
GVHD-free graft failure-free survival (GGFS) 1, 3, and 5 years post transplant Time from transplant to primary or secondary graft failure and death due to grade 3-4 acute GVHD not responsive to seven days of high dose steroids
Incidence of Chronic Graft versus-host disease 1 and 2 years post transplant Cumulative incidence of chronic graft versus host disease at 1 and 2 years post transplant.
transplant-related mortality 180 days and 1 year post transplant Time from transplant to transplant-related death
disease-free survival 1, 3, and 5 years post transplant Time from transplant to death of any cause or disease relapse.
Trial Locations
- Locations (2)
National Institutes of Health Clinical Center
🇺🇸Bethesda, Maryland, United States
National Marrow Donor Program
🇺🇸Minneapolis, Minnesota, United States