Chemotherapy, Antithymocyte Globulin, Total-Body Irradiation, and a Donor Umbilical Cord Blood Transplant and Donor Stem Cell Transplant in Treating Patients With Severe Aplastic Anemia or Myelodysplastic Syndromes - NCT00608413-20892(Clinical Trial 201569)
ClinicalConnection.com has recently undergone an update and this page may no longer be up-to-date. Please Search For Clinical Trials to view the most current clinical trials listings.
| City: |
|
Bethesda |
|
State:
|
|
MD |
| Zip Code: |
|
20892 |
| Conditions: |
|
Leukemia - Myelodysplastic Syndromes - Nonmalignant Neoplasm |
| Purpose: |
|
RATIONALE: Giving chemotherapy, antithymocyte globulin, and total-body irradiation before a
donor umbilical cord blood transplant and a donor peripheral stem cell transplant helps stop
the growth of abnormal cells. It also stops the patient's immune system from rejecting the
donor's stem cells. When the healthy stem cells from a donor are infused into the patient
they may help the patient's bone marrow make stem cells, red blood cells, white blood cells,
and platelets. Sometimes the transplanted cells from a donor can make an immune response
against the body's normal cells. Giving tacrolimus, mycophenolate mofetil, and prednisone or
methylprednisolone before and after transplant may stop this from happening.
PURPOSE: This phase II trial is studying how well giving cyclophosphamide together with
fludarabine, antithymocyte globulin, and total-body irradiation followed by donor umbilical
cord blood transplant and donor peripheral stem cell transplant works in treating patients
with severe aplastic anemia or myelodysplastic syndromes associated with severe neutropenia
that has not responded to immunosuppressive therapy.
|
| Study summary: |
|
OBJECTIVES:
Primary
- To evaluate the potential of > 80% of patients with severe aplastic anemia or
myelodysplastic syndromes associated with severe neutropenia refractory to
immunosuppressive therapy to achieve engraftment of the umbilical cord blood (UCB) unit
(defined as UCB-derived absolute neutrophil count [ANC] ≥ 500 cells/μL) by day 42 when
treated with a nonmyeloablative conditioning regimen comprising cyclophosphamide,
fludarabine phosphate, anti-thymocyte globulin, and total-body irradiation followed by
donor umbilical cord blood transplantation and haploidentical related donor CD34+
peripheral blood stem cell transplantation.
Secondary
- To evaluate ANC recovery rate (ANC ≥ 500 cells/μL) on day 22.
- To evaluate the safety of this novel transplant regimen (non-hematologic toxicities).
- To evaluate treatment-related mortality on day 100 and day 200.
- To determine the incidence and severity of acute and chronic graft-versus-host disease
(GVHD) following treatment with this transplant regimen.
OUTLINE:
- Nonmyeloablative preparative conditioning regimen: Patients receive cyclophosphamide IV
over 60 minutes once daily on days -7 and -6, fludarabine phosphate IV over 30 minutes
once daily on days -5 to -1, and anti-thymocyte globulin IV over 4 hours once daily on
days -5 to -2. Patients also receive a single dose of total-body irradiation over 30
minutes on day -1.
- Donor stem cell transplantation: Patients undergo donor umbilical cord blood
transplantation and haploidentical related donor CD34+ peripheral blood stem cell
transplantation on day 0.
- Graft-versus-host-disease (GVHD) prophylaxis: Patients receive tacrolimus IV
continuously over 24 hours or orally twice daily beginning on day -4 and continuing for
at least 6 months and mycophenolate mofetil IV or orally twice daily beginning on day 0
and continuing for 100 days. Patients also receive oral prednisone or
methylprednisolone IV beginning on day -5 (prior to the first dose of ATG) and
continuing until day 19.
After completion of study treatment, patients are followed every 3 months for 3 years, every
6 months for 2 years, and then annually thereafter. |
| Criteria: |
|
DISEASE CHARACTERISTICS:
- Diagnosed of 1 of the following:
- Severe aplastic anemia characterized by all of the following:
- Bone marrow cellularity < 30% (excluding lymphocytes)
- Transfusion dependence for platelets and/or RBCs
- Neutropenia (absolute neutrophil count [ANC] < 500 cells/μL)
- Failed at least two forms of immunosuppressive therapy
- Myelodysplastic syndromes characterized by all of the following:
- Refractory anemia (RA) OR RA with ringed sideroblasts (RARS)
- Neutropenia (ANC < 500 cells/μL)
- Refractory to one or more lines of therapy
- History of 1 or more opportunistic infections related to neutropenia
- At least one HLA-haploidentical (≥ 3/6 HLA matched) related donor (2-75 years old)
available
- No HLA identical or 5/6 HLA-matched related stem cell donor available
- At least 2 x 10^6 CD34+ cells/kg required from haploidentical related donor
- No haploidentical related donor with sickling hemoglobinopathies, including
HbSS, HbAS, or HbSC
- At least one 4/6 HLA-matched (HLA-A, B, and DR loci) umbilical cord blood (UCB) unit
from the National Marrow Donor Program available
- UCB unit must contain a minimum total nucleated cells (TNC) (prior to thawing)
of ≥ 1.5 x 10^7 cells/kg of recipient body weight
- UCB unit must contain ≥ 1.7 x 10^5 CD34+ cells/kg (prior to thawing) if the
minimum criterion of TNC is not met
- Not deemed to be a candidate for a 6/6 HLA-matched related or unrelated stem cell
transplantation
PATIENT CHARACTERISTICS:
- ECOG performance status 0-1
- Transaminases ≤ 5 times upper limit of normal
- Serum bilirubin ≤ 4 mg/dL
- Creatinine clearance ≥ 50 mL/min
- DLCO ≥ 40% predicted
- Left ventricular ejection fraction ≥ 40% by ECHO OR ≥ 30% by MUGA
- HIV-negative
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No major anticipated illness or organ failure incompatible with survival from
transplant
- No severe psychiatric illness or mental deficiency sufficiently severe as to make
compliance with the transplant regimen unlikely and make informed consent impossible
- No active infection not adequately responding to appropriate therapy
- No history of a malignant disease that is liable to relapse or progress within 5
years
PRIOR CONCURRENT THERAPY:
- At least 45 days since prior immunosuppressive therapy with horse anti-thymocyte
globulin (ATG) or rat-ATG |
|
|
|
|
|
|
|
|
If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
|
| Trials Alerts: |
|
If you would like to be
notified of new clinical trials as they become available please
register for a free account.
|
|
| Data Source: |
|
ClinicalTrials.gov |
| Date Processed: |
|
August 16, 2010 |
Modifications to
this listing: |
|
Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
|
|
|
|
|
|
|
|