Ignite Creation Date:
2024-05-05 @ 11:32 AM
Last Modification Date:
2024-10-26 @ 9:09 AM
Study NCT ID:
NCT00074490
Status:
TERMINATED
Last Update Posted:
2018-12-31
First Post:
2006-06-19
Brief Title:
Donor Stem Cell Transplant With No or Low-Intensity Chemotherapy Using Sirolimus and Treated Immune Cells to Treat Blood and Lymph Cancers
Sponsor:
National Cancer Institute NCI
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Allogeneic HSCT Without Preparative Chemotherapy or With Low-Intensity Preparative Chemotherapy Using Sirolimus and Sirolimus-Generated Donor Th2 Cells for Therapy of Refractory Leukemia Lymphoma Myeloma or Myelodysplastic Syndrome
Status:
TERMINATED
Status Verified Date:
2018-12
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Premature closure due to inability to accrue to ARM IVD cohorts 1 and 2
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Background
Patients with cancers of the blood and immune system often benefit from transplants of stem cells from a genetically well-matched sibling However severe problems may follow these transplants because of the high-dose chemotherapy and radiation that accompany the procedure Also donated immune cells sometimes attack healthy tissues in a reaction called graft-versus-host disease GVHD damaging organs such as the liver intestines and skin To reduce toxicity of high-dose preparative chemotherapy this study performs allogeneic transplant after low doses of chemotherapy In an attempt to improve anti-tumor effects without increasing GVHD this study uses donor immune cells T helper 2 Th2 cells grown in the laboratory some patients will receive standard donor immune cells not grown in laboratory All patients will receive immune modulating drugs sirolimus and cyclosporine to prevent GVHD
Objective
To determine the safety treatment effects and rate of GVHD in patients receiving transplants that use low-intensity chemotherapy sirolimus plus cyclosporine and transplant booster with either Th2 cells or standard immune cells
Eligibility
Patients 16 to 75 years of age with acute or chronic leukemia non-Hodgkins lymphoma Hodgkins disease multiple myeloma or myelodysplastic syndrome
Patients must have a suitable genetically matched sibling donor and adequate kidney heart and lung function
Design The protocol has three treatment groups cohort 1 Th2 booster at two weeks post-transplant cohort 2 standard T cell booster at two weeks post-transplant cohort 3 multiple infusion of Th2 cells
Condition Hematologic Neoplasms Myeloproliferative Disorders
Intervention Biological therapeutic allogeneic lymphocytes
Drug Sirolimus
Study Type Interventional
Study Design Primary Purpose Treatment
Phase Phase II
Patients with cancers of the blood and immune system often benefit from transplants of stem cells from a genetically well-matched sibling However severe problems may follow these transplants because of the high-dose chemotherapy and radiation that accompany the procedure Also donated immune cells sometimes attack healthy tissues in a reaction called graft-versus-host disease GVHD damaging organs such as the liver intestines and skin To reduce toxicity of high-dose preparative chemotherapy this study performs allogeneic transplant after low doses of chemotherapy In an attempt to improve anti-tumor effects without increasing GVHD this study uses donor immune cells T helper 2 Th2 cells grown in the laboratory some patients will receive standard donor immune cells not grown in laboratory All patients will receive immune modulating drugs sirolimus and cyclosporine to prevent GVHD
Objective
To determine the safety treatment effects and rate of GVHD in patients receiving transplants that use low-intensity chemotherapy sirolimus plus cyclosporine and transplant booster with either Th2 cells or standard immune cells
Eligibility
Patients 16 to 75 years of age with acute or chronic leukemia non-Hodgkins lymphoma Hodgkins disease multiple myeloma or myelodysplastic syndrome
Patients must have a suitable genetically matched sibling donor and adequate kidney heart and lung function
Design The protocol has three treatment groups cohort 1 Th2 booster at two weeks post-transplant cohort 2 standard T cell booster at two weeks post-transplant cohort 3 multiple infusion of Th2 cells
Condition Hematologic Neoplasms Myeloproliferative Disorders
Intervention Biological therapeutic allogeneic lymphocytes
Drug Sirolimus
Study Type Interventional
Study Design Primary Purpose Treatment
Phase Phase II
Detailed Description:
Background
In protocol 99-C-0143 we evaluated a new approach to allogeneic hematopoietic stem cell transplant HSCT that involved intensive host T cell ablation and graft augmentation with in vitro generated donor T helper 2 Th2 cells Rapid full donor engraftment occurred with this regimen however grade II to IV acute graft versus host disease GVHD was not significantly reduced in Th2 cell recipients In an attempt to improve clinical results using Th2 cell graft engineering this second-generation Th2 cell clinical trial was developed that incorporates the following interventions 1 In an attempt to reduce transplant-related toxicity this protocol now uses a very low-intensity host preparative chemotherapy 2 In an attempt to reduce GVHD this study will utilize Th2 cells expanded in the presence of the immune modulation agent rapamycin sirolimus as murine Th2 cells grown in rapamycin reduce GVHD more effectively than control Th2 cells 3 To further reduce GVHD subjects will receive a short-course of sirolimus therapy in addition to standard cyclosporine GVHD prophylaxis and 4 Using this novel low-intensity transplant platform compare in a preliminary manner the post-transplant outcome of patients receiving pre-emptive donor lymphocyte infusion DLI using either Th2 cells or unmanipulated donor T cells
Objectives
In the setting of human leukocyte antigen HLA-matched sibling allogeneic HSCT using GVHD prophylaxis of cyclosporine and short-course sirolimus compare in a preliminary manner the safety feasibility alloengraftment clinical anti-tumor effects and GVHD rate of low-intensity Preparative Chemotherapy with pre-emptive DLI using either Th2 cells or unmanipulated T cells at day 14 post-HSCT
Eligibility
Subjects that are 16 to 75 years of age that have a suitable 66 HLA-matched sibling donor are potentially eligible Subjects with a diagnosis of acute or chronic leukemia non-Hodgkins lymphoma Hodgkins disease multiple myeloma or myelodysplastic syndrome are potentially eligible Adequate kidney cardiac and pulmonary function are required
Design
Patients age 18 or older with lymphoma all types or chronic lymphocytic leukemia will be randomized just prior to the transplant regimen to receive DLI with either donor Th2 cells cohort 1 or unmanipulated T cells cohort 2 n10 patients will be accrued to each arm provided that stopping rules pertaining to excessive GVHD or graft rejection are not met For these randomized patients the preparative regimen will consist of low-intensity fludarabine 120 mgm2 plus cyclophosphamide 1200 mgm2 and GVHD prophylaxis will consist of short-course high-dose sirolimus followed by maintenance cyclosporine Cohorts 1 and 2 will be compared in a preliminary manner with respect to their post-transplant outcome in particular a conversion of mixed chimerism to predominant donor chimerism b rate and severity of classical acute and late acute GVHD at the day 100 and day 180 post-transplant time points and c time to induction of leukemialymphoma remission if entering transplant with disease or time to relapse if entering transplant in remission
Patients with non-lymphoma diagnoses patients with lymphoma that are under the age of 18 and lymphoma patients that are projected to be unable to complete the protocol-defined therapy through day 180 post-transplant will not be randomized but will be treated on cohort 3 n40 which will evaluate transplantation without the FluCy preparative regimen and with pre-emptive Th2 cell DLI The primary objective of cohort 3 is to evaluate whether transplantation without a preparative regimen will reduce the rate of acute GVHD associated with Th2 cell DLI from 41 the rate observed with the fludarabinecyclophosphamide FluCy preparative regimen to a rate of 15 6 cases out of 40
In protocol 99-C-0143 we evaluated a new approach to allogeneic hematopoietic stem cell transplant HSCT that involved intensive host T cell ablation and graft augmentation with in vitro generated donor T helper 2 Th2 cells Rapid full donor engraftment occurred with this regimen however grade II to IV acute graft versus host disease GVHD was not significantly reduced in Th2 cell recipients In an attempt to improve clinical results using Th2 cell graft engineering this second-generation Th2 cell clinical trial was developed that incorporates the following interventions 1 In an attempt to reduce transplant-related toxicity this protocol now uses a very low-intensity host preparative chemotherapy 2 In an attempt to reduce GVHD this study will utilize Th2 cells expanded in the presence of the immune modulation agent rapamycin sirolimus as murine Th2 cells grown in rapamycin reduce GVHD more effectively than control Th2 cells 3 To further reduce GVHD subjects will receive a short-course of sirolimus therapy in addition to standard cyclosporine GVHD prophylaxis and 4 Using this novel low-intensity transplant platform compare in a preliminary manner the post-transplant outcome of patients receiving pre-emptive donor lymphocyte infusion DLI using either Th2 cells or unmanipulated donor T cells
Objectives
In the setting of human leukocyte antigen HLA-matched sibling allogeneic HSCT using GVHD prophylaxis of cyclosporine and short-course sirolimus compare in a preliminary manner the safety feasibility alloengraftment clinical anti-tumor effects and GVHD rate of low-intensity Preparative Chemotherapy with pre-emptive DLI using either Th2 cells or unmanipulated T cells at day 14 post-HSCT
Eligibility
Subjects that are 16 to 75 years of age that have a suitable 66 HLA-matched sibling donor are potentially eligible Subjects with a diagnosis of acute or chronic leukemia non-Hodgkins lymphoma Hodgkins disease multiple myeloma or myelodysplastic syndrome are potentially eligible Adequate kidney cardiac and pulmonary function are required
Design
Patients age 18 or older with lymphoma all types or chronic lymphocytic leukemia will be randomized just prior to the transplant regimen to receive DLI with either donor Th2 cells cohort 1 or unmanipulated T cells cohort 2 n10 patients will be accrued to each arm provided that stopping rules pertaining to excessive GVHD or graft rejection are not met For these randomized patients the preparative regimen will consist of low-intensity fludarabine 120 mgm2 plus cyclophosphamide 1200 mgm2 and GVHD prophylaxis will consist of short-course high-dose sirolimus followed by maintenance cyclosporine Cohorts 1 and 2 will be compared in a preliminary manner with respect to their post-transplant outcome in particular a conversion of mixed chimerism to predominant donor chimerism b rate and severity of classical acute and late acute GVHD at the day 100 and day 180 post-transplant time points and c time to induction of leukemialymphoma remission if entering transplant with disease or time to relapse if entering transplant in remission
Patients with non-lymphoma diagnoses patients with lymphoma that are under the age of 18 and lymphoma patients that are projected to be unable to complete the protocol-defined therapy through day 180 post-transplant will not be randomized but will be treated on cohort 3 n40 which will evaluate transplantation without the FluCy preparative regimen and with pre-emptive Th2 cell DLI The primary objective of cohort 3 is to evaluate whether transplantation without a preparative regimen will reduce the rate of acute GVHD associated with Th2 cell DLI from 41 the rate observed with the fludarabinecyclophosphamide FluCy preparative regimen to a rate of 15 6 cases out of 40
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 04-C-0055 | None | None | None |