Ignite Creation Date:
2024-05-05 @ 7:02 PM
Last Modification Date:
2024-10-26 @ 9:40 AM
Study NCT ID:
NCT00590460
Status:
TERMINATED
Last Update Posted:
2018-05-24
First Post:
2007-12-26
Brief Title:
Antibody Conditioning Regimen For Allogeneic Donor Stem Cell Transplantation Of Patients With Fanconi Anemia
Sponsor:
Baylor College of Medicine
Organization:
Baylor College of Medicine
Study Overview
Official Title:
Cd45 Yth-24 and Yth 54 and Cd52 Campath-1H Monoclonal Antibody Conditioning Regimen for Allogeneic Donor Stem Cell Transplantation of Patients With Fanconi Anemia
Status:
TERMINATED
Status Verified Date:
2018-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
slow accrual
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Mafia
Brief Summary:
The purpose of this study is to discover whether children and adults with Fanconi anemia FA can be safely and effectively transplanted with Human Leukocyte Antigen HLA mismatched up to one haplotype HLA-matched sibling or unrelated donor stem cells when leukocytolytic monoclonal antibodies are the sole conditioning agents patients receiving an HLA mismatched transplant will receive Fludarabine as part of the conditioning regimen Three monoclonal antibodies MAb will be used in combination Two of them YTH 24 and YTH 54 are rat antibodies directed against two contiguous epitopes on the CD45 common leucocyte antigen They have been safely administered as part of the conditioning regimen for 12 patients receiving allografts HLA matched and mismatched at this center They produce a transient depletion of 90 circulating leucocytes The third MAb is Campath 1H a humanized rat anti-CD52 MAb This MAb has been widely used to treat B cell chronic lymphocytic leukemia B-CLL and more recently has been safely given at this and other centers as part of a sub-ablative conditioning regimen to patients with malignant disease Because these MAb produce both profound immunosuppression and significant though transient myelodestruction we believe they may be useful as the sole conditioning regimen in patients with Fanconi anemia in whom the use of conventional chemotherapeutic agents for conditioning produces a high rate of short and long term toxicity We anticipate MAb mediated subablative conditioning will permit engraftment in a high percentage of these patients with little or no immediate or long term toxicity Campath IH persists in vivo for several days after administration and so will be present over the transplant period to deplete donor T cells as partial graft versus host disease GvHD prophylaxis Additional GvHD prophylaxis will be provided by administration of the medication FK506
Detailed Description:
If clinically feasible no aplasia no active malignancy the recipients marrow will be harvested and cryopreserved as a back up for use if non-engraftmentrejection is followed by failure to undergo autologous reconstitution
For HLA Mismatched donors harvested peripheral blood stem cells will be enriched for CD34 cells using the Clinimacs CD34 Reagent system
Fludarabine will be given as 5 daily intravenous infusions Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion Diphenydramine will be administered intravenously every 4 hours during the period of the course of each infusion
Day -8 Campath 1H as per CAGT SOP Fludarabine 30 mgm2 -7 Campath 1H as per CAGT SOP Fludarabine 30 mgm2 -6 Campath 1H as per CAGT SOP Fludarabine 30 mgm2 -5 YTH 2454 400ugkg over 6 hr Fludarabine 30 mgm2 -4 YTH 2454 400ugkg over 6 hr Fludarabine 30 mgm2 -3 YTH 2454 400ugkg over 6 hr -2 YTH 2454 400ugkg over 6 hr -1 -0 Stem Cell Infusion
GVHD prophylaxis will be achieved through positive selection for CD34 resulting in 3 log T cell depletion Previous reports have indicated that there is a low frequency of severe Grade IIIV GvHD after haploidentical transplants if recipients receive stem cell populations containing 5 x 10e4 CD3 positive T cells We hope to achieve such levels with our CD34 enrichment protocol However pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10e4 CD3ve T cellskg recipient weight In addition Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity in vivo
For HLA Mismatched donors harvested peripheral blood stem cells will be enriched for CD34 cells using the Clinimacs CD34 Reagent system
Fludarabine will be given as 5 daily intravenous infusions Campath-1H will be given as 3 daily intravenous infusions and will be followed by Anti-CD45 which will be given as four daily intravenous infusions that will be completed two days prior to stem cell infusion Diphenydramine will be administered intravenously every 4 hours during the period of the course of each infusion
Day -8 Campath 1H as per CAGT SOP Fludarabine 30 mgm2 -7 Campath 1H as per CAGT SOP Fludarabine 30 mgm2 -6 Campath 1H as per CAGT SOP Fludarabine 30 mgm2 -5 YTH 2454 400ugkg over 6 hr Fludarabine 30 mgm2 -4 YTH 2454 400ugkg over 6 hr Fludarabine 30 mgm2 -3 YTH 2454 400ugkg over 6 hr -2 YTH 2454 400ugkg over 6 hr -1 -0 Stem Cell Infusion
GVHD prophylaxis will be achieved through positive selection for CD34 resulting in 3 log T cell depletion Previous reports have indicated that there is a low frequency of severe Grade IIIV GvHD after haploidentical transplants if recipients receive stem cell populations containing 5 x 10e4 CD3 positive T cells We hope to achieve such levels with our CD34 enrichment protocol However pharmacologic prophylaxis will be added if the CD34 selected product contains more than 5 x 10e4 CD3ve T cellskg recipient weight In addition Campath 1H persists in the recipient circulation through the immediate transplant period and will contribute anti-GVHD activity in vivo
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