The standard Johns Hopkins' regimen will be used in study subjects, with the use of donor peripheral blood stem cells, rather than marrow. Clinical outcomes will be defined while focusing efforts on immune reconstitution focusing on immune checkpoint regulators after a related haploidentical stem cell transplant.
We propose a clinical trial to define clinical endpoints, including engraftment, 100-day survival and one year survival (Objective #1). We will characterize the incidence, prevalence and function of immune checkpoint regulators in patients' blood and bone marrow following transplantation (Objective #2). We will correlate these laboratory results with clinical outcomes and the incidence of GVHD. As an exploratory aim, in those patients experiencing GVHD and requiring treatment, we will define the frequency/expression of 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
21
14.5 mg/kg for 2 days (days -6, -5) and then 50 mg/kg for two days (days 3, 4)
30 mg/m2 daily for 5 days
200 centigray (cGy) for one day (day -1)
1 mg IV daily, (or the oral equivalent) adjusted to achieve a level between 5 and 15 ng/ml. If there is no evidence of GVHD, discontinue Tacrolimus by Day 180.
dose at 15 mg/kg po three times per day (maximum dose of 3 grams/day). Stop Cellcept at Day 35 following transplantation.
5 mcg/kg/d starting day 5 and continue until Absolute Neutrophil Count (ANC) \> 1000/mcL for 3 days.
cell dose goal: \< 5 x 106 Hematopoietic progenitor cell antigen CD34+ cells/kg recipient weight
Dartmouth Hitchcock Medical Center, Norris Cotton Cancer Center
Lebanon, New Hampshire, United States
Number of Participants Who Survived to 100-Days Post-transplant
Define 100-day survival of subjects
Time frame: 100 days post date of peripheral blood transplant
Number of Participants Who Survived to One Year Post-Transplant.
Define one year survival of subjects
Time frame: One year post date of peripheral blood transplant
Number of Participants Who Experienced a Successful Engraftment
Define number of subjects who experience a successful engraftment: Defined as absolute neutrophil count \> 500/mm3 and platelets \> 20,000/mcl for three consecutive days (count first day as engraftment)
Time frame: Post-peripheral blood transplant
Number of Participants Who Achieved a Response to Treatment at 100 Days
Define response to treatment at 100 days post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
Time frame: 100 days post-peripheral blood transplant
Number of Participants Who Achieved a Response to Treatment at One Year
Define response to treatment at one year post-peripheral blood transplant. The Standard International Criteria for responses for each disease will be used, based on CIBMTR (Center for International Blood and Marrow Transplant Research) criteria.
Time frame: One year post-peripheral blood transplant
Number of Participants Who Experienced Toxicities Associated With This Treatment Regimen
Define subjects who experienced toxicities associated with this treatment regimen
Time frame: Post-peripheral blood transplant
Number of Participants Who Had Incidence of Acute GVHD
Define subjects who had incidence of acute GVHD
Time frame: Post-peripheral blood transplant
Number of Participants Who Had Incidence of Chronic GVHD
Define subjects who had incidence of chronic GVHD
Time frame: Post-peripheral blood transplant
Number of Participants Who Experienced Donor-Recipient Chimerism Following Transplant at Days 30, 60, and 90.
Define subjects who experience donor-recipient chimerism following transplant at days 30, 60 and 90. All patients were assessed for donor-recipient chimerism at days 30, 60, and 90, but only one patient experienced chimerism. Day 90 for this patient is reported.
Time frame: Days 30, 60, and 90 post-peripheral blood transplant
Number of Participants Who Experienced Treatment-Related Mortality Within the First 100 Days
Define subjects who experienced treatment-related mortality within the first 100 days post-peripheral blood transplant
Time frame: 100 days post-peripheral blood transplant
Immune Checkpoint Regulators - Incidence
To characterize the incidence of immune checkpoint regulators (V-domain Ig Suppressor of T-cell Activation, cytotoxic T-lymphocyte-associated protein 4 \[CTLA\], Programmed cell death protein 1 \[PD-1\]) during early immune recovery following an allogeneic stem cell transplant.
Time frame: Days 30, 60, and 90 post-transplant
Myeloid-derived Suppressor Cells (MDSCs) After Graft vs. Host Disease (GVHD) Diagnosis - Checkpoint Regulator Expression
In those patients experiencing GVHD, the study team will define the checkpoint regulator expression on MDSCs
Time frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
MDSCs After GVHD Diagnosis - Peripheral Blood Mononuclear Cells
In those patients experiencing GVHD, the study team will define the peripheral blood mononuclear cells and myeloid subsets.
Time frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
MDSCs After GVHD Diagnosis - Myeloid Subsets Using Flow Cytometry
In those patients experiencing GVHD, the study team will define the myeloid subsets.
Time frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
MDSCs After GVHD Diagnosis - Frequency
In those patients experiencing GVHD, the study team will define the MDSCs frequency.
Time frame: Post-transplant through study completion or death, assessed up to 3 years post-transplant
Immune Checkpoint Regulators - Prevalence
To characterize the prevalence of immune checkpoint regulators (VISTA, CTLA-4, PD-1) during early immune recovery following an allogeneic stem cell transplant.
Time frame: Days 30, 60, and 90 post-transplant
Immune Checkpoint Regulators - Function
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Flow cytometry will be used to characterize the function of immune checkpoint regulators (VISTA, CTLA-4, PD-1) during early immune recovery following an allogeneic stem cell transplant.
Time frame: Days 30, 60, and 90 post-transplant