The participants are being asked to take part in this clinical trial because the participant have a lymphoid or myeloid based cancer diagnosis that requires a bone marrow transplant. Primary Objectives To estimate the incidence of severe acute GVHD (saGVHD) using a prophylaxis regimen with no calcineurin inhibitors after day +60 post first allogeneic Human Leukocyte antigen (HLA)-matched sibling or unrelated donor HCT for hematological malignancies. Secondary objective Determine the cumulative incidence of relapse, NRM, chronic GVHD, and OS in study participants at one year post-transplant. Exploratory objectives * To evaluate the pharmacokinetic/pharmacodynamic (PK/PD) profiles of ruxolitinib, fludarabine, and rATG. * To assess immune reconstitution in study participants within the first year post-HCT.
The investigator propose to employ two preparative regimens based on the underlying hematological malignancy. For hematological malignancies of the lymphoid lineage we will use a standard preparative regimen consisting of Total Body Irradiation and cyclophosphamide (TBI/Cy), unless TBI is contraindicated. For myeloid malignancies we will use thiotepa, busulfan, and fludarabine (TBF), a preparative regimen that has been associated with a reduced risk of relapse and trend for improved survival with comparable NRM in comparison to busulfan and cyclophosphamide (BuCy), our current regimen. All HCT recipients will receive cyclosporine in combination with methotrexate and ruxolitinib as GVHD prophylaxis. Recipients of MUD HCT will receive rATG for additional immunosuppression as is standard for unrelated donor transplants
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
3
Day +40 Dosage and Route of Administration-Ruxolitinib tablets should be administered orally BID, approximately every 12 hours, continuously, Oral
Days -3 and -2 Dosage and Route of Administration-Mesna is dosed based on the cyclophosphamide dose and generally administered in fractionated doses at approximately 20% of the total cyclophosphamide dose, Intravenous.
Days -3, -2 and -1 Dosage and Route of Administration-(7 mg/kg total dose); intravenous.
Day -1 Dosage and Route of Administration-3 mg/kg; dose will be adjusted to maintain a steady concentration between 250-350 ng/mL or trough concentration between 175-250 ng/mL when transitioned to intermittent dosing.
Days -3 and -2 Dosage and Route of Administration-60 mg/kg for 2 consecutive days, (120 mg/kg total dose); intravenous.
Days -4, -3 and -2 Dosage and Route of Administration-50 mg/m2 daily for 3 consecutive days (150 mg/m2 total dose) intravenous
Days +1, +3, +6 and +11 Dosage and Route of Administration-10 mg/m2/dose, intravenous
Days -7, -6, -5 and -4 6.2.3 Target Dose 1200 cGy total dose delivered 150 cGy per treatment fraction delivered BID over 4 days with 6 MV photons. Dose rate should be \< 10 cGy/min in patients treated at extended SSD (450-500 cm) in the TBI couch and will be less than 15 cGy/min in young children and infants treated at extended SSD (200-220 cm) on the floor. Intra-fraction interval should be 6 hours. Custom posteriorly placed (PA only) partial transmission lung shields (blocks) will be used to reduce the average dose to the lung to approximately 1000 cGy total dose. An additional 400 cGy supplemental testicular radiation delivered in 2 fractions of 200 cGy delivered for males with lymphoid lineage leukemia.
Day 0
Days -4, -3 and -2 Dosage and Route of Administration-3.2 mg/kg/day; intravenous.
Days -6 and -5 Dosage and Route of Administration-(10 mg/kg total dose); intravenous
St. Jude Children's Research Hospital
Memphis, Tennessee, United States
Proportion of saGVHD Using a ProphylaxisRegimen With no Calcineurin Inhibitors After Day 100 Post First Allogeneic HLA-Matched Sibling or Unrelated Donor HCT for Hematological Malignancies.
Development of Severe Acute GVHD (saGVHD) at or before Day 100 post transplant is considered as an event. Severe acute GVHD is defined as grade II-IVGVHD. Acute graft-vs-host disease will be evaluated using the standard grading criteria.
Time frame: 100 days post transplant
Cumulative Incidence of Overall Survival (OS)
The one-year survival is defined by the participant who has not died within one year after post transplantation. The rate is calculated by computing the ratio between total number of one year survival patients and the total number of patients.
Time frame: One-year post-transplantation.
Cumulative Incidence of Relapse
Bone marrow studies for disease status evaluation will be performed at 1-year post-transplant. Testing will include a research evaluation for minimal residual disease.
Time frame: One-year post-transplantation.
Cumulative Incidence of Non Relapse Mortality (NRM)
Non-relapse mortality is death without evidence of disease relapse or progression. The rate is calculated by computing the ratio between total number of NRM patients and the total number of patients.
Time frame: One-year post-transplantation.
Cumulative Incidence of Chronic GVHD
Chronic graft-vs-host disease will be evaluated using the standard grading criteria.
Time frame: One-year post-transplantation.
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