This research is being done to learn more about nonmyeloablative bone marrow transplantation (BMT), also known as a "mini" transplant for patients with blood cancers, using bone marrow from a relative.
The main goal is to learn whether a drug called tacrolimus, which is an immune-lowering drug (an immunosuppressant) given after transplant to help prevent certain complications, can be given safely for a shorter period of time than it has been in the past. At the present time there are few or no cures for your type of disease outside of a bone marrow transplant. The bone marrow for this transplant comes from a relative who is a half-match or "haplo" match to you. Possible donors include parents, siblings, and children. In order to help the bone marrow grow, or "take", inside your body, you will receive chemotherapy and radiation before the transplant. After the transplant you will receive high doses of cyclophosphamide (Cytoxan®) along with other medications to lower the immune system, tacrolimus. These medications may lower the risk of graft versus host disease (GVHD) and of your body rejecting the bone marrow graft.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
127
Days -6 and -5: 14.5 mg/kg/day IV. Days 3 and 4: 50 mg/kg/day IV.
Days -6, -5, -4, -3, and -2: 30 mg/m\^2/day IV.
Day -1: 200 centigray in one fraction.
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland, United States
Safety of reduced-dose tacrolimus as assessed by Percentage of Participants with severe graft versus host disease (GVHD)
Percentage of participants with severe graft versus host disease (GVHD) defined as grade III-IV acute GVHD or extensive chronic GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+). Chronic GVHD is defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity. Higher scores indicate more severe disease. Scores are not totaled or added up.
Time frame: Day 5 - Day 120
Tolerability of tacrolimus as assessed by percentage of participants with treatment-emergent adverse events
Percentage of participants with grade 3-4 toxicity by CTCAE 4.0 attributable to tacrolimus.
Time frame: Up to 120 days
Percentage of participants experiencing acute GVHD
Percentage of participants with grade II-IV and III-IV acute GVHD. Acute GVHD is defined by the Przepiorka criteria, which stages the degree of organ involvement in the skin, liver, and gastrointestinal (GI) tract, based on severity, with Stage 1+ being least severe and stage 4+ being the most severe. Grading of acute GVHD is as follows: Grade I (skin involvement stages 1+ to 2+, with no liver or GI involvement), Grade II (skin involvement stages 1+ to 3+, liver 1+, GI tract 1+), Grade III (skin involvement stages 2+ to 3+, liver 1+, GI tract 2+ to 4+), Grade IV (skin involvement stages 4+, Liver 4+).
Time frame: Up to 7 years
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Days 5 to 35: 15 mg/kg PO three times per day; max daily dose 1 g.
Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 60.
Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 90.
Begin dosing at 1 mg IV daily on Day 5. Dose is titrated according to serum levels. Stop at Day 120.
Donor stem cells infused IV on Day 0.
Percentage of participants experiencing chronic GVHD
Percentage of participants with chronic GVHD. Chronic GVHD is defined by the NIH consensus criteria. This system gives scores from 0 to 3 for Karnofsky performance score, skin, mouth, eyes, gastrointestinal, liver, lungs, joints, and genitals, as well as an overall severity (mild, moderate, or severe). Higher scores indicate more severe disease. Scores are not totalled or added up.
Time frame: Up to 7 years
Disease relapse
Percentage of participants experiencing disease relapse or progression.
Time frame: Up to 7 years
Non-relapse mortality
Percentage of participants who died for any reason other than disease relapse or progression.
Time frame: Up to 7 years
Use of immunosuppression
Percentage of participants who: required use of steroids; required use of non-steroid immunosuppression; and who were able to discontinue immunosuppression after starting treatment.
Time frame: Up to 2 years
Survival
Percentage of participants who are alive with and without disease relapse or progression.
Time frame: Up to 7 years
Chimerism
Percentage of participants who had \>=95% donor chimerism.
Time frame: 30 and 60 days
Engraftment
Percentage of participants who had successful engraftment of neutrophils and platelets.
Time frame: 30 and 60 days