Hemoglobinopathies Clinical Trial
Official title:
A Study of Hematopoietic Stem Cell Transplantation (HSCT) in Non-Malignant Disease Using a Reduced-Intensity Preparatory Regime
The hypothesis for this study is that a preparative regimen that maximizes host immunosuppression without myeloablation will be well tolerated and sufficient for engraftment of donor hematopoietic cells. It is also to determine major toxicities from these conditioning regimens, within the first 100 days after transplantation.
Status | Recruiting |
Enrollment | 220 |
Est. completion date | December 2031 |
Est. primary completion date | December 2026 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 20 Years |
Eligibility | Inclusion Criteria: Stratum 1: Patient must have non-malignant disorder, excluding thalassemia. Must be receiving a 8/8 HLA-matched bone marrow, related or unrelated Stratum 2: Patient must have thalassemia receiving 8/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated. Stratum 3: Patient must have a hemoglobinopathy receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated. Stratum 4: Patient must have a non-malignant disorder (excluding hemoglobinopathy) receiving 7/8 HLA-matched bone marrow or 5-8/8 HLA-matched UCB. Related or unrelated. All strata: - Recipient age < 21 years - Lansky/Karnofsky >/= 40 - Adequate pulmonary, renal, liver, and other organ function as defined in protocol - Negative pregnancy test - Adequate total nucleated cell or CD34+ dose of product as defined in protocol - If sickle cell, Hemoglobin S <30% Exclusion Criteria: - HIV positive - Invasive infection - Pregnancy/lactating |
Country | Name | City | State |
---|---|---|---|
Canada | University of Calgary | Calgary | |
United States | Carolinas Medical Center | Charlotte | North Carolina |
United States | Children's Memorial Hospital | Chicago | Illinois |
United States | Hackensack University Medical Center | Hackensack | New Jersey |
United States | Indiana University School of Medicine | Indianapolis | Indiana |
United States | Miami Children's Hospital | Miami | Florida |
United States | University of Miami | Miami | Florida |
United States | Yale School of Medicine | New Haven | Connecticut |
United States | Columbia University Medical Center | New York | New York |
United States | The University of Oklahoma | Oklahoma City | Oklahoma |
United States | Children's Hospital of Orange County | Orange | California |
United States | Phoenix Children's Hospital | Phoenix | Arizona |
United States | St. Louis University | Saint Louis | Missouri |
United States | Washington University School of Medicine (in St. Louis) | Saint Louis | Missouri |
United States | All Children's Hospital | Saint Petersburg | Florida |
United States | Texas Transplant Institute | San Antonio | Texas |
United States | University of California | San Diego | California |
United States | George Washington University School of Medicine | Washington | District of Columbia |
Lead Sponsor | Collaborator |
---|---|
Washington University School of Medicine | St. Louis Children's Hospital |
United States, Canada,
Bhatla D, Davies SM, Shenoy S, Harris RE, Crockett M, Shoultz L, Smolarek T, Bleesing J, Hansen M, Jodele S, Jordan M, Filipovich AH, Mehta PA. Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syn — View Citation
Hansen MD, Filipovich AH, Davies SM, Mehta P, Bleesing J, Jodele S, Hayashi R, Barnes Y, Shenoy S. Allogeneic hematopoietic cell transplantation (HCT) in Hurler's syndrome using a reduced intensity preparative regimen. Bone Marrow Transplant. 2008 Feb;41( — View Citation
Rao A, Kamani N, Filipovich A, Lee SM, Davies SM, Dalal J, Shenoy S. Successful bone marrow transplantation for IPEX syndrome after reduced-intensity conditioning. Blood. 2007 Jan 1;109(1):383-5. doi: 10.1182/blood-2006-05-025072. Epub 2006 Sep 21. — View Citation
Shenoy S, Grossman WJ, DiPersio J, Yu LC, Wilson D, Barnes YJ, Mohanakumar T, Rao A, Hayashi RJ. A novel reduced-intensity stem cell transplant regimen for nonmalignant disorders. Bone Marrow Transplant. 2005 Feb;35(4):345-52. doi: 10.1038/sj.bmt.1704795. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Donor engraftment as measured by chimerism | Engraftment is measured in myeloid and lymphoid lineage cells | 100 days post-transplant | |
Primary | Major toxicities as graded by the CTC v4 | Toxicity monitoring includes unanticipated side effects (new) and all severe irreversible toxicities Grade 3 and above unexpected Grade 4 and above - all toxicities that are possibly, probably or definitely related to protocol therapy All deaths irrespective of attribution | 100 days post-transplant | |
Secondary | Time to neutrophil and platelet engraftment as measured by complete blood counts | Defined as an ANC >500/microliter and platelets >20,000 or 50,000/microliter depending on disorder | Post transplant | |
Secondary | Incidence of acute graft-versus-host disease as measured by protocol grading scale | aGVHD - involving the skin, gut and liver. Classified according to grading described by Thomas et al. NEJM 1975; 292:895-902 | 100 days post-transplant | |
Secondary | Incidence of chronic graft-versus-host disease as measured by protocol grading scale | cGVHD classified per Schulman et al. Am J Med 69: 204-17, 1980. | 2 years post-transplant | |
Secondary | Long-term donor engraftment by donor chimerism | Donor chimerism is determined by PCR analysis after cell separation into lymphoid and myeloid lineage cells using antibodies. Can also be detected by FISH analysis in the event of donor and recipient sex discrepancy. | 2 years post-transplant | |
Secondary | Immune reconstitution by laboratory evaluations | Immune reconstitution detected by absolute numbers of T cell phenotypes, B cells and NK cells. T cell function determined by proliferative response to mitogens. B cell function determined by evaluating anti-tetanus antibody titers. | 1 year post-transplant | |
Secondary | Overall and disease free survival | Overall survival is defined as survival with or without disease Event free survival is defined as disease free, severe GVHD free survival, monitoring quality of life and relevant parameters. | 2 years post-transplant |
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