Campath/Fludarabine/Melphalan Transplant Conditioning for Non-Malignant Diseases
- Conditions
- Hematologic, Immune, or Bone Marrow DisordersHemoglobinopathiesMetabolic DisordersNon-malignant Disorders
- Registration Number
- NCT00920972
- Lead Sponsor
- Washington University School of Medicine
- Brief Summary
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.
- Detailed Description
The study uses reduced intensity conditioning that is immune suppressive to achieve donor cell engraftment without exposure to radiation or high dose chemotherapy in children with non-malignant disorders. The intent is to minimize early and late regimen related toxicities in the context of a reduced intensity regimen.
In addition to maximizing opportunity for donor cell engraftment, the trial seeks to minimize toxicities associated with transplant such as graft versus host disease and employs GVHD prophylaxis that seeks to decrease rates of acute and chronic GVHD in the setting of matched and mismatched donor stem cell transplants from marrow and cord blood sources.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 220
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%
- HIV positive
- Invasive infection
- Pregnancy/lactating
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Primary Outcome Measures
Name Time Method Major toxicities as graded by the CTC v4 100 days post-transplant 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
Donor engraftment as measured by chimerism 100 days post-transplant Engraftment is measured in myeloid and lymphoid lineage cells
- Secondary Outcome Measures
Name Time Method Long-term donor engraftment by donor chimerism 2 years post-transplant 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.
Incidence of chronic graft-versus-host disease as measured by protocol grading scale 2 years post-transplant cGVHD classified per Schulman et al. Am J Med 69: 204-17, 1980.
Immune reconstitution by laboratory evaluations 1 year post-transplant 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.
Overall and disease free survival 2 years post-transplant 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.
Time to neutrophil and platelet engraftment as measured by complete blood counts Post transplant Defined as an ANC \>500/microliter and platelets \>20,000 or 50,000/microliter depending on disorder
Incidence of acute graft-versus-host disease as measured by protocol grading scale 100 days post-transplant aGVHD - involving the skin, gut and liver. Classified according to grading described by Thomas et al. NEJM 1975; 292:895-902
Trial Locations
- Locations (18)
Miami Children's Hospital
🇺🇸Miami, Florida, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
St. Louis University
🇺🇸Saint Louis, Missouri, United States
Carolinas Medical Center
🇺🇸Charlotte, North Carolina, United States
The University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
All Children's Hospital
🇺🇸Saint Petersburg, Florida, United States
George Washington University School of Medicine
🇺🇸Washington, District of Columbia, United States
University of Miami
🇺🇸Miami, Florida, United States
Phoenix Children's Hospital
🇺🇸Phoenix, Arizona, United States
University of Calgary
🇨🇦Calgary, Canada
Yale School of Medicine
🇺🇸New Haven, Connecticut, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
University of California
🇺🇸San Diego, California, United States
Children's Memorial Hospital
🇺🇸Chicago, Illinois, United States
Indiana University School of Medicine
🇺🇸Indianapolis, Indiana, United States
Washington University School of Medicine (in St. Louis)
🇺🇸Saint Louis, Missouri, United States
Columbia University Medical Center
🇺🇸New York, New York, United States
Texas Transplant Institute
🇺🇸San Antonio, Texas, United States