Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant
- Conditions
- LeukemiaMyelodysplastic Syndromes
- Interventions
- Biological: anti-thymocyte globulinBiological: peripheral blood lymphocyte therapyProcedure: allogeneic hematopoietic stem cell transplantationProcedure: in vitro-treated peripheral blood stem cell transplantationRadiation: total-body irradiation
- Registration Number
- NCT00376480
- Lead Sponsor
- Dana-Farber Cancer Institute
- 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 patient's immune system from rejecting the donor's stem cells. When the healthy stem cells from a donor are infused into the patient they may help the patient's 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 body's 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 19
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description administration of adoptive donor lymphocyte infusion allogeneic hematopoietic stem cell transplantation administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion in vitro-treated peripheral blood stem cell transplantation administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion total-body irradiation administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion anti-thymocyte globulin administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion peripheral blood lymphocyte therapy administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion fludarabine phosphate administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion thiotepa administration of donor lymphocytes made using costimulatory blockade ex vivo administration of adoptive donor lymphocyte infusion methylprednisolone administration of donor lymphocytes made using costimulatory blockade ex vivo
- Primary Outcome Measures
Name Time Method Feasibility of making and administering the adoptive T cell product from conditioning through administration of anergized cells on day 35-42 ability to collect sufficient cells, make anergized product with good viability, without contamination and infuse per study toxicity of the conditioning regimen, the likelihood of engraftment, and the subsequent percentage of individuals who would be eligible to receive aDLI were determined.
Safety of administering the adoptive T cell product on day 35-42 post haploidentical transplant the period from aDLI infusion through D100 rates of graft failure with CD34 selected product, adverse and severe adverse reactions attributable to infusion of anergized donor cells, including fever, hypotension, acute graft vs host disease, organ dysfunction
Alloreactivity engendered by administering the adoptive T cell product from cell infusion through day 100 occurrence and severity of acute GVHD
- Secondary Outcome Measures
Name Time Method Efficacy in restoring adaptive immunity from aDLI thorough 1 year incidence of viral infection and type of immune reconstitution by phenotype and function of T cells
Trial Locations
- Locations (6)
M. D. Anderson Cancer Center at University of Texas
🇺🇸Houston, Texas, United States
University of Florida Health Science Center - Gainesville
🇺🇸Gainesville, Florida, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Childrens Hospital Los Angeles
🇺🇸Los Angeles, California, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States