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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
220
Day -50 to -21: Hydroxyurea 30mg/kg PO q day Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... Day -8: Fludarabine 30mg/m2 IV... Day -7: Fludarabine 30mg/m2 IV... Day -6: Fludarabine 30mg/m2 IV... Day -5: Fludarabine 30mg/m2 IV... Day -4: Fludarabine 30mg/m2 IV... Day -3: Melphalan 140 mg/m2 IV... (dose modifications for patients \<10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion on Day 0...
Day -50 to -21: Hydroxyurea 30mg/kg PO q day… Day -22: Campath-1H 3 mg IV or SQ... Day -21: Campath-1H 10 mg IV or SQ... Day -20: Campath-1H 15 mg IV or SQ... Day -19: Campath-1H 20 mg IV or SQ... Day -8: Fludarabine 30mg/m2 IV... Day -7: Fludarabine 30mg/m2 IV... Day -6: Fludarabine 30mg/m2 IV... Day -5: Fludarabine 30mg/m2 IV... Day -4: Fludarabine 30mg/m2 IV... Day -4: Thiotepa 8mg/kg IV… Day -3: Melphalan 140 mg/m2 IV... (dose modifications for patients \<10 kgs) Procedure/Surgery: Hematopoietic stem cell infusion on day 0...
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +5: Abatacept 10mg/kg IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV
Day -3: Begin Tacrolimus or cyclosporine Begin MMF Day -1: Abatacept 10mg/kg IV Day +1: Methotrexate 7.5mg/m2 IV Day +3: Methotrexate 7.5mg/m2 IV Day +5: Abatacept 10mg/kg IV Day +6: Methotrexate 7.5mg/m2 IV Day +14: Abatacept 10mg/kg IV Day +28: Abatacept 10mg/kg IV Day +60: Abatacept 10mg/kg IV Day +100: Abatacept 10mg/kg IV Day +180: Abatacept 10mg/kg IV Day +270: Abatacept 10mg/kg IV Day +365: Abatacept 10mg/kg IV
Phoenix Children's Hospital
Phoenix, Arizona, United States
ACTIVE_NOT_RECRUITINGChildren's Hospital of Orange County
Orange, California, United States
ACTIVE_NOT_RECRUITINGUniversity of California
San Diego, California, United States
ACTIVE_NOT_RECRUITINGYale School of Medicine
New Haven, Connecticut, United States
ACTIVE_NOT_RECRUITINGDonor engraftment as measured by chimerism
Engraftment is measured in myeloid and lymphoid lineage cells
Time frame: 100 days post-transplant
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
Time frame: 100 days post-transplant
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
Time frame: Post transplant
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
Time frame: 100 days post-transplant
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.
Time frame: 2 years post-transplant
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.
Time frame: 2 years post-transplant
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.
Time frame: 1 year post-transplant
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.
Time frame: 2 years post-transplant
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
George Washington University School of Medicine
Washington D.C., District of Columbia, United States
ACTIVE_NOT_RECRUITINGNemours Children's Health
Jacksonville, Florida, United States
COMPLETEDUniversity of Miami
Miami, Florida, United States
ACTIVE_NOT_RECRUITINGMiami Children's Hospital
Miami, Florida, United States
COMPLETEDAll Children's Hospital
St. Petersburg, Florida, United States
COMPLETEDChildren's Memorial Hospital
Chicago, Illinois, United States
COMPLETED...and 18 more locations