Ignite Creation Date:
2024-05-05 @ 11:04 PM
Last Modification Date:
2024-10-26 @ 10:28 AM
Study NCT ID:
NCT01247701
Status:
COMPLETED
Last Update Posted:
2022-06-08
First Post:
2010-11-22
Brief Title:
Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Umbilical Cord Blood Transplant for Children With Myeloid Hematological Malignancies UCAML
Status:
COMPLETED
Status Verified Date:
2022-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
UCAML
Brief Summary:
In this study the investigators will use busulfan and cyclophosphamide BuCy backbone with the addition of fludarabine as the preparative Stem Cell Transplant SCT regimen As an attempt to improve engraftment rate and reduce infections the investigators are going to incorporate fludarabine in the conditioning regimen The use of a BuCy backbone has been widely used and comparable to total body irradiation and cyclophosphamide CyTBI regimen
Encouraging data on adding fludarabine to the SCT regimen have been reported A fludarabine-based conditioning regimen with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality Regimen-related toxicity is believed to be a major contributing factor to GVHD Therefore this approach may also lead to reduced GVHD as some investigators have suggested
In an attempt to decrease the rate of viral infection and reactivation the investigators will avoid ATG Thymoglobulin Campath anti-CD52 and instead administer Mycophenolate Mofetil MMF The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATGCampath The investigators anticipate that the removal of ATGCampath will facilitate immune reconstitution more efficiently after receiving a UCBT
Encouraging data on adding fludarabine to the SCT regimen have been reported A fludarabine-based conditioning regimen with adequate immunosuppressive activity could conceivably allow engraftment of stem cells from alternative donors in hematologic malignancies patients with acceptable engraftment rates and low transplant-related mortality Regimen-related toxicity is believed to be a major contributing factor to GVHD Therefore this approach may also lead to reduced GVHD as some investigators have suggested
In an attempt to decrease the rate of viral infection and reactivation the investigators will avoid ATG Thymoglobulin Campath anti-CD52 and instead administer Mycophenolate Mofetil MMF The addition of fludarabine should compensate any increase risk of graft failure with the removal of the ATGCampath The investigators anticipate that the removal of ATGCampath will facilitate immune reconstitution more efficiently after receiving a UCBT
Detailed Description:
The following will be given as the conditioning regimen for the transplant
BUSULFAN Busulfan intravenous BUSULFEX dosing will be as follows patients 12 kg 11 mgkgdose IV every 6 hours for 16 doses total patients 12 kg 08 mgkgdose IV every 6 hours for 16 doses Administration and pharmacokinetic monitoring will be performed as per standard practice Anticonvulsants will be given in accordance with standard Blood and Marrow Transplant Program recommendations
CYCLOPHOSPHAMIDE Cyclophosphamide 50 mgkgdose will be given IV on Days -5 - 4 -3 and -2 over 1 hour The total dose to be given over 4 days is 200 mgkg Mesna will be given in accordance with standard Blood and Marrow Transplant
FLUDARABINE Fludarabine will be given IV daily over 1 hour for 3 days Dosing will be as follows for patients 10 kg 13 mgkg for patients 10 kg 40 mgm2 Preparation administration and monitoring will be according to standard practice procedure
POST-TRANSPLANT IMMUNOSUPPRESSION
CSA will begin on Day -3 For children 40 kg the initial dose will be 25 mgkg IV over 2 hours every 12 hours Dose adjustments will be made to maintain levels above 200 ngmL Levels will be done on Day 0 and then as clinical indicated CSA will be tapered per institutional SOP Once the patient can tolerate oral medications and has a normal gastrointestinal transit time CSA will be converted to an oral form
MMF will begin on Day 0 at a dose of 15 mgKg IV or orally TID and will be discontinued on Day 45 unless GVHD is present
CNS Disease Patients with CNS relapse or primary CNS disease that is symptomatic or associated to radiological changes will receive additional irradiation to the craniospinal axis
SUPPORTIVE CARE
Supportive care will be provided as per standard practice of the Blood and Marrow Stem Cell Transplant program at the Texas Childrens Hospital including all prophylactic and therapeutic clinical care issues These practices may be modified if necessary for any individual patient in order to provide optimum care for that particular patient
IVIG Intravenous immunoglobulin 500 mgkg per dose will be given monthly until discontinuation of GVHD therapy and documentation of antibody production
CB-CTLs Patients enrolled in this protocol may also be eligible for infusion of CB-derived multivirus-specific CTL to provide virus-specific immune reconstitution and treatment of viral infections after CBT
EVALUATIONS DURING THE STUDY
Screening Procedures Pre-HCT
Physical examination
Pregnancy test
Complete blood count and chemistries
Electrocardiogram
Echocardiograph
PTPTTFibrinogenAnti-Thrombin IIIvon Willebrand Factor
Viral tests
Bone marrow aspirate and biopsyLumbar puncture
Renal Function GFR
Lumbar puncture will be performed
Pulmonary Function test
EVALUATIONS BETWEEN DAY 0 AND DAY 100
Physical examination
Complete blood count and chemistries
LytesBUNCr
Peripheral blood for STRs or FISH analysis for molecular diagnostics
Lymphocyte phenotype testing and lymphoproliferative responses
Bone marrow aspirate and biopsy for assessment of leukemia status and UCB engraftment
Lumbar puncture
Immunoglobulins
EVALUATIONS AFTER DAY 100
Physical examination
Complete blood count and chemistries
LytesBUNCr
Serum chemistries
Peripheral blood with assessment of engraftment by STRs or FISH analysis and enzyme levels
Echocardiograph with LVEF
Bone marrow aspirate and biopsy assessment of leukemia status and UCB engraftment
Lymphocyte phenotype testing CD3 CD4 CD8 CD19 and CD56 and lymphoproliferative responses
Immunoglobulins
FOLLOW-UP INTERVAL
Patients will be seen in the hospital everyday until discharge After discharge from the hospital the patient will be following on the BMT clinics on a regular basis as recommended by the primary physician
BUSULFAN Busulfan intravenous BUSULFEX dosing will be as follows patients 12 kg 11 mgkgdose IV every 6 hours for 16 doses total patients 12 kg 08 mgkgdose IV every 6 hours for 16 doses Administration and pharmacokinetic monitoring will be performed as per standard practice Anticonvulsants will be given in accordance with standard Blood and Marrow Transplant Program recommendations
CYCLOPHOSPHAMIDE Cyclophosphamide 50 mgkgdose will be given IV on Days -5 - 4 -3 and -2 over 1 hour The total dose to be given over 4 days is 200 mgkg Mesna will be given in accordance with standard Blood and Marrow Transplant
FLUDARABINE Fludarabine will be given IV daily over 1 hour for 3 days Dosing will be as follows for patients 10 kg 13 mgkg for patients 10 kg 40 mgm2 Preparation administration and monitoring will be according to standard practice procedure
POST-TRANSPLANT IMMUNOSUPPRESSION
CSA will begin on Day -3 For children 40 kg the initial dose will be 25 mgkg IV over 2 hours every 12 hours Dose adjustments will be made to maintain levels above 200 ngmL Levels will be done on Day 0 and then as clinical indicated CSA will be tapered per institutional SOP Once the patient can tolerate oral medications and has a normal gastrointestinal transit time CSA will be converted to an oral form
MMF will begin on Day 0 at a dose of 15 mgKg IV or orally TID and will be discontinued on Day 45 unless GVHD is present
CNS Disease Patients with CNS relapse or primary CNS disease that is symptomatic or associated to radiological changes will receive additional irradiation to the craniospinal axis
SUPPORTIVE CARE
Supportive care will be provided as per standard practice of the Blood and Marrow Stem Cell Transplant program at the Texas Childrens Hospital including all prophylactic and therapeutic clinical care issues These practices may be modified if necessary for any individual patient in order to provide optimum care for that particular patient
IVIG Intravenous immunoglobulin 500 mgkg per dose will be given monthly until discontinuation of GVHD therapy and documentation of antibody production
CB-CTLs Patients enrolled in this protocol may also be eligible for infusion of CB-derived multivirus-specific CTL to provide virus-specific immune reconstitution and treatment of viral infections after CBT
EVALUATIONS DURING THE STUDY
Screening Procedures Pre-HCT
Physical examination
Pregnancy test
Complete blood count and chemistries
Electrocardiogram
Echocardiograph
PTPTTFibrinogenAnti-Thrombin IIIvon Willebrand Factor
Viral tests
Bone marrow aspirate and biopsyLumbar puncture
Renal Function GFR
Lumbar puncture will be performed
Pulmonary Function test
EVALUATIONS BETWEEN DAY 0 AND DAY 100
Physical examination
Complete blood count and chemistries
LytesBUNCr
Peripheral blood for STRs or FISH analysis for molecular diagnostics
Lymphocyte phenotype testing and lymphoproliferative responses
Bone marrow aspirate and biopsy for assessment of leukemia status and UCB engraftment
Lumbar puncture
Immunoglobulins
EVALUATIONS AFTER DAY 100
Physical examination
Complete blood count and chemistries
LytesBUNCr
Serum chemistries
Peripheral blood with assessment of engraftment by STRs or FISH analysis and enzyme levels
Echocardiograph with LVEF
Bone marrow aspirate and biopsy assessment of leukemia status and UCB engraftment
Lymphocyte phenotype testing CD3 CD4 CD8 CD19 and CD56 and lymphoproliferative responses
Immunoglobulins
FOLLOW-UP INTERVAL
Patients will be seen in the hospital everyday until discharge After discharge from the hospital the patient will be following on the BMT clinics on a regular basis as recommended by the primary physician
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None