Severe Aplastic Anemia Clinical Trial
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
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.
If clinically feasible (no aplasia, no active malignancy), the recipients marrow will be
harvested and cryopreserved as a back up for use if non-engraftment/rejection 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 mg/m2 -7 Campath 1H as per CAGT SOP
Fludarabine 30 mg/m2 -6 Campath 1H as per CAGT SOP Fludarabine 30 mg/m2 -5 YTH 24/54 400ug/kg
over 6 hr Fludarabine 30 mg/m2 -4 YTH 24/54 400ug/kg over 6 hr Fludarabine 30 mg/m2 -3 YTH
24/54 400ug/kg over 6 hr -2 YTH 24/54 400ug/kg 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 II/IV) 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 CD3+ve T cells/kg recipient weight. In addition,
Campath 1H persists in the recipient circulation through the immediate transplant period and
will contribute anti-GVHD activity, in vivo.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT02828592 -
Haploidentical Bone Marrow Transplant With Post-Transplant Cyclophosphamide for Patients With Severe Aplastic Anemia
|
Phase 2 | |
Completed |
NCT02833805 -
NMA Haplo or MUD BMT for Newly Diagnosed Severe Aplastic Anemia
|
Phase 2 | |
Terminated |
NCT01319851 -
Alefacept and Allogeneic Hematopoietic Stem Cell Transplantation
|
N/A | |
Completed |
NCT00004143 -
Allogeneic Mixed Chimerism Stem Cell Transplant Using Campath for Hemoglobinopathies & Bone Marrow Failure Syndromes
|
Phase 2 | |
Recruiting |
NCT05012111 -
Natural History of Acquired and Inherited Bone Marrow Failure Syndromes
|
||
Recruiting |
NCT03836690 -
Transfer of Effector Memory T Cells (Tem) Following Allogeneic Stem Cell Transplantation
|
Phase 1 | |
Recruiting |
NCT06039436 -
Conditioning Regimen Containing Low Dose ATG for The Treatment of Acquired SAA Receiving sUCBT
|
||
Enrolling by invitation |
NCT05049668 -
RACE 2: a Long Term Follow-up of Patients Participating in the RACE Trial
|
||
Recruiting |
NCT01472055 -
Pharmacokinetic Study of Fludarabine in Pediatric Hematopoietic Stem Cell Transplantation
|
Phase 2 | |
Recruiting |
NCT01351545 -
A Multicenter Access and Distribution Protocol for Unlicensed Cryopreserved Cord Blood Units (CBUs)
|
||
Completed |
NCT01703169 -
Efficacy and Safety of Eltrombopag In Patients With Severe and Very Severe Aplastic Anemia
|
Phase 2 | |
Withdrawn |
NCT01129323 -
Reduced-Intensity Preparative Regimen for Allogeneic Stem Cell Transplantation in Patients With Severe Aplastic Anemia
|
N/A | |
Completed |
NCT00516152 -
Phase II Study Evaluating Busulfan and Fludarabine as Preparative Therapy in Adults With Hematopoietic Disorders Undergoing MUD SCT
|
Phase 2 | |
Recruiting |
NCT06069180 -
The Optimization of Conditioning Regimen for HLA Matched HSCT in SAA
|
Phase 4 | |
Recruiting |
NCT03579875 -
Alpha/Beta TCD HCT in Patients With Inherited BMF Disorders
|
Phase 2 | |
Recruiting |
NCT05720234 -
Avatrombopag Combined With IST as First-line Treatment for SAA
|
Phase 2 | |
Recruiting |
NCT04304820 -
Early Initiation of Oral Therapy With Cyclosporine and Eltrombopag for Treatment Naive Severe Aplastic Anemia (SAA)
|
Phase 2 | |
Terminated |
NCT00358657 -
Fludarabine Phosphate, Cyclophosphamide, and Total-Body Irradiation Followed by Donor Bone Marrow Transplant and Cyclophosphamide, Mycophenolate Mofetil, Tacrolimus, and Sirolimus in Treating Patients With Primary Immunodeficiency Disorders or Noncancerous Inherited Disorders
|
Phase 2 | |
Completed |
NCT02998645 -
Eltrombopag Combined With Cyclosporine as First Line Therapy in Patients With Severe Acquired Aplastic Anemia
|
Phase 2 | |
Active, not recruiting |
NCT03825744 -
Hetrombopag or Placebo in Treatment-Naive Severe Aplastic Anemia
|
Phase 3 |