Laboratory-Treated Lymphocyte Infusion After Haploidentical Donor Stem Cell Transplant
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00376480|
Recruitment Status : Completed
First Posted : September 15, 2006
Last Update Posted : July 3, 2019
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.
|Condition or disease||Intervention/treatment||Phase|
|Leukemia Myelodysplastic Syndromes||Biological: anti-thymocyte globulin Biological: peripheral blood lymphocyte therapy Drug: fludarabine phosphate Drug: methylprednisolone Drug: thiotepa Procedure: allogeneic hematopoietic stem cell transplantation Procedure: in vitro-treated peripheral blood stem cell transplantation Radiation: total-body irradiation||Phase 1|
- 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.
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||19 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
|Actual Study Start Date :||June 2005|
|Actual Primary Completion Date :||June 2010|
|Actual Study Completion Date :||May 16, 2018|
Experimental: administration of adoptive donor lymphocyte infusion
administration of donor lymphocytes made using costimulatory blockade ex vivo
Biological: anti-thymocyte globulin
Biological: peripheral blood lymphocyte therapy
Drug: fludarabine phosphate
Procedure: allogeneic hematopoietic stem cell transplantation
Procedure: in vitro-treated peripheral blood stem cell transplantation
Radiation: total-body irradiation
- Feasibility of making and administering the adoptive T cell product [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: from cell infusion through day 100 ]occurrence and severity of acute GVHD
- Efficacy in restoring adaptive immunity [ Time Frame: from aDLI thorough 1 year ]incidence of viral infection and type of immune reconstitution by phenotype and function of T cells
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00376480
|United States, California|
|Childrens Hospital Los Angeles|
|Los Angeles, California, United States, 90027-0700|
|United States, Florida|
|University of Florida Health Science Center - Gainesville|
|Gainesville, Florida, United States, 32610|
|United States, Massachusetts|
|Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|Dana Farber Cancer Institute|
|Boston, Massachusetts, United States, 02115|
|United States, Texas|
|M. D. Anderson Cancer Center at University of Texas|
|Houston, Texas, United States, 77030-4009|
|Study Chair:||Eva Guinan, MD||Dana-Farber Cancer Institute|