This study is examining a chemotherapy regimen and immune suppressive medications in the setting of an allogeneic stem cell transplant. A pilot clinical trial to characterize the incidence, prevalence and function of myeloid-derived suppressor cells (MDSCs) and immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation \[VISTA\], cytotoxic T-lymphocyte- associated protein 4 \[CTLA-4\], programmed death-ligand 1 \[PD-L1\]) during early immune recovery following an allogeneic stem cell transplant. The site will use a myeloablative regimen of fludarabine with busulfan, adopted from CALGB 100801, to define clinical endpoints, including engraftment, 100 day survival and one year survival (Objective #1). The site will characterize the incidence, prevalence and function of MDSCs and immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). The site will correlate these laboratory results with clinical outcomes and the incidence of graft-versus-host disease (GVHD). As an exploratory aim, in those patients experiencing GVHD and requiring treatment, the site will define the MDSCs frequency and checkpoint regulator expression and correlate these results with the patient's response to GVHD therapy.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
Fludarabine: 30 mg/m2 daily for 5 days
Busulfan: 100 mg/m2 daily for 4 days
Rabbit ATG: Related donors: 1.5 mg/kg daily x 2 days (on days -6 and -5) Unrelated donors: 1.5 mg/kg on day - 6 2 mg/kg on day -5 2.5 mg/kg on day -4
Methotrexate: Related donors: 5 mg/m2 on days 1, 3 and 6 Unrelated donors: 5 mg/m2 on days 1, 3, 6 and 11
Dartmouth-Hitchcock Medical Center
Lebanon, New Hampshire, United States
Number of patients who are surviving at 100-Days post-transplant
100-Day survival of patients
Time frame: 100 Days
Time to marrow engraftment
Time to marrow engraftment (defined as absolute neutrophil count \> 500/mm3 and platelets \> 20,000/mcl for three consecutive days (count first day as engraftment)
Time frame: 100 Days
Assessing all subjects' response to treatment at 100 days post-transplant
Response to treatment at 100 days using standard international response criteria, based on CIBMTR definitions.
Time frame: 100 Days
Assessing all subjects' response to treatment at 1 year post-transplant
Response to treatment at one year using standard international response criteria, based on CIBMTR definitions.
Time frame: 365 Days
Assessing all subjects' survival at 1 year post-transplant
One year survival
Time frame: 365 Days
Assessing the mortality rate of patients in the first 100 days post-transplant
Treatment-related mortality in the first 100 days
Time frame: 100 Days
Assessing the number of treatment-related adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 365 Days
Collecting the incidents of GvHD experienced by patients post-transplant
Incidence of acute and chronic GVHD
Time frame: 365 Days
Assessing the donor-chimerism at 30, 60 and 90 days post-transplant
Donor-recipient chimerism following transplant at Days 30, 60 and 90.
Time frame: 30, 60, and 90 Days
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