Ignite Creation Date:
2024-05-05 @ 5:03 PM
Last Modification Date:
2024-10-26 @ 9:27 AM
Study NCT ID:
NCT00376480
Status:
COMPLETED
Last Update Posted:
2019-07-05
First Post:
2006-09-13
Brief Title:
Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant
Sponsor:
Dana-Farber Cancer Institute
Organization:
Dana-Farber Cancer Institute
Study Overview
Official Title:
Delayed Infusion of Ex Vivo Anergized Peripheral Blood Mononuclear Cells Following CD34 Selected Peripheral Blood Stem Cell Transplantation From a Haploidentical Donor for Patients With Acute Leukemia and Myelodysplasia
Status:
COMPLETED
Status Verified Date:
2019-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
RATIONALE Giving total-body irradiation and chemotherapy such as thiotepa and fludarabine before a donor stem cell transplant helps stop the growth of cancer or abnormal cells It also helps stop the patients immune system from rejecting the donors stem cells When the healthy stem cells from a donor are infused into the patient they may help the patients bone marrow make stem cells red blood cells white blood cells and platelets Sometimes the transplanted cells from a donor can make an immune response against the bodys normal cells Giving methylprednisolone and antithymocyte globulin before transplant and peripheral blood cells that have been treated in the laboratory after transplant may stop this from happening
PURPOSE This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases
PURPOSE This phase I trial is studying the side effects and best dose of laboratory-treated peripheral blood cell infusion after donor stem cell transplant in treating patients with hematologic cancers or other diseases
Detailed Description:
OBJECTIVES
Primary
Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells PBMC after CD34 cluster designation 34-selected megadose haploidentical hematopoietic stem cell transplantation HSCT in patients with hematopoietic cancers or other diseases
Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients
Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization
Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC
Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease
Secondary
Evaluate in vitro the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization
Assess in vitro the function of immune cells engrafted in these patients
Assess in vitro whether alloantigen hyporesponsive donor T cells are present in these patients
Develop preliminarily in vitro data on the extent of pathogen-specific immunity and its rate of recovery
Describe the patterns of opportunistic infections in these patients
OUTLINE This is a multicenter dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells PBMC Patients who are treated on any dose level except dose level 1 are stratified according to age under 17 pediatric vs 17 and over adult
Myeloablative conditioning regimen Patients undergo total-body irradiation twice daily on days -11 to -9 Patients also receive thiotepa IV over 4 hours on days -8 and -7 fludarabine phosphate IV over 30 minutes on days -7 to -3 and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3
Allogeneic peripheral blood stem cell transplantation PBSCT Patients undergo CD34-selected PBSCT on day 0
Ex vivo anergized allogeneic PBMC infusion If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease patients undergo allogeneic or autologous PBMC infusion on day 35 or 42
Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose MTD is determined The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity
After completion of study patients are followed periodically for 2 years
PROJECTED ACCRUAL A total of 40 patients will be accrued for this study
Primary
Establish the feasibility of delayed infusion of ex vivo anergized donor peripheral blood mononuclear cells PBMC after CD34 cluster designation 34-selected megadose haploidentical hematopoietic stem cell transplantation HSCT in patients with hematopoietic cancers or other diseases
Determine the feasibility of collecting parental allogeneic stimulator cells to induce anergy to the nonshared donor-recipient haplotype in these patients
Determine the feasibility of collecting donor PBMC as a source of T cells for ex vivo anergization
Determine the number of transplanted individuals who meet the criteria for proceeding to delayed infusion of ex vivo anergized donor PBMC
Establish the safety of delayed infusion of ex vivo anergized donor PBMC by establishing the maximum number of donor T cells that can be infused without unacceptable graft-versus-host disease
Secondary
Evaluate in vitro the induction and specificity of alloantigen hyporesponsiveness in donor PBMC after ex vivo anergization
Assess in vitro the function of immune cells engrafted in these patients
Assess in vitro whether alloantigen hyporesponsive donor T cells are present in these patients
Develop preliminarily in vitro data on the extent of pathogen-specific immunity and its rate of recovery
Describe the patterns of opportunistic infections in these patients
OUTLINE This is a multicenter dose-escalation study of ex vivo anergized allogeneic peripheral blood mononuclear cells PBMC Patients who are treated on any dose level except dose level 1 are stratified according to age under 17 pediatric vs 17 and over adult
Myeloablative conditioning regimen Patients undergo total-body irradiation twice daily on days -11 to -9 Patients also receive thiotepa IV over 4 hours on days -8 and -7 fludarabine phosphate IV over 30 minutes on days -7 to -3 and anti-thymocyte globulin IV over 8 hours and methylprednisolone IV over 15-30 minutes on days -6 to -3
Allogeneic peripheral blood stem cell transplantation PBSCT Patients undergo CD34-selected PBSCT on day 0
Ex vivo anergized allogeneic PBMC infusion If cells have engrafted and patients are free of active uncontrolled infection and graft-vs-host disease patients undergo allogeneic or autologous PBMC infusion on day 35 or 42
Cohorts of 3-8 patients receive escalating doses of ex vivo anergized allogeneic PBMCs until the maximum tolerated dose MTD is determined The MTD is defined as the dose at which 2 of 5 or 3 of 8 patients experience dose-limiting toxicity
After completion of study patients are followed periodically for 2 years
PROJECTED ACCRUAL A total of 40 patients will be accrued for this study
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
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 |
|---|---|---|---|
| MDA-2005-0695 | US NIH GrantContract | None | httpsreporternihgovquickSearchP30CA006516 |
| P01CA100265 | NIH | None | None |
| P30CA006516 | NIH | None | None |