Our primary objective is to determine if it is feasible for SAA patients to be transplanted using non-myeloablative conditioning and post transplantation cyclophosphamide with partially HLA-mismatched donors.
This research is being done to find out if bone marrow transplantation (BMT) followed by chemotherapy will help people with aplastic anemia who have failed other treatments. You have a severe, life threatening disease (severe aplastic anemia) in your bone marrow. Your disease has come back or not responded after receiving one or more immunosuppressive treatments. High dose chemotherapy followed by bone marrow transplantation (BMT) has been used to treat blood diseases like yours but complications from Graft vs. Host disease (GVHD) and graft failure have limited the survival for those people. A small study done at Johns Hopkins has shown that in subjects with other diseases (blood cancers) some immunosuppressive drugs given after the BMT have decreased how often subjects had complications of GVHD and engraftment failure. People with aplastic anemia who have refractory disease (not responding to standard treatment) may join.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
18
Day 0
0.5 mg/kg IV on Day -9 2 mg/kg IV on Days -8, -7
30 mg/M2 IV on days -6 to -2
The Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Medical College of Wisconsin/Children's Hospital of Wisconsin
Milwaukee, Wisconsin, United States
Is This Type of Transplantation for Severe Aplastic Anemia Feasible and Safe?
Feasibility will be met with the following conditions: the patient has the transplant, is assessed for the safety endpoint, and survives one year. The safety monitoring plan is included to monitor graft failure (day 60), grade 2-4 acute graft versus host disease (day100), 6 month mortality (day 180), and chronic graft versus host disease (day 180).
Time frame: 1 year
Number of Patients That Have Survived at One Year
Time frame: 1 year
Number of Patients That Have Acheived Full Donor Chimerism by Day 60 After Transplant
Donor chimerism will be measured in the peripheral blood around day 30 and day 60. Patients with \>5% donor chimerism around day 60 will be considered as having engrafted.
Time frame: 60 days
Number of Patients That Expired Due to Non-relapsed-related Mortality Following Transplant
Time frame: 1 year
Number of Participants With Major Toxicities Related to Transplant
Time frame: 1 year
Number of Patients That Expired Due to Transplant Related Mortality
Time frame: 1 year
Number of Patients With Primary or Secondary Graft Failure Following Transplant
Graft failure: \< 5% donor chimerism in blood and/or bone marrow on \~Day 30 or after and on all subsequent measurements. Primary graft failure: \< 5% donor chimerism in blood and/or bone marrow by \~ Day 56 Secondary graft failure: achievement of \> 5% donor chimerism, followed by sustained \<5% donor chimerism in blood and/or bone marrow.
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14.5 mg/kg IV on days -6, -5, 3, 4
200 cGy on day -1
40 mg/kg IV on days 3, 4
For patients 18 years or older, tacrolimus will be given per institutional standards; may be increased or later changed to a PO BID schedule. Treatment to continue until Day 365 or longer if GVHD present
15 mg/kg PO/IV TID beginning on day 5 through day 35
Time frame: 1 year
Number of Participants With Grade II-IV or Grade III-IV Acute GVHD
Participants were graded during clinical visits based on evidence and extent of skin rash, liver involvement, and GI tract involvement
Time frame: 1 year
Participants With Chronic GVHD at One Year
Time frame: 1 year
Length of Time Required for Patients to Recover ANC and Platelet Counts After Transplant
CBC drawn daily with a WBC differential once the total WBC is greater than 100 until ANC \> 500 for three days or two consecutive measurements over a three day period; then CBC drawn weekly with differential.
Time frame: 1 year
Participants That Were GVHD Free, Relapse Free Survival (GRFS)
Time frame: 1 year