A Pilot Trial Examining Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic Stem Cell Transplant Recipients Using Myeloablative Busulfan and Fludarabine
Overview
- Phase
- Phase 1
- Intervention
- Methotrexate
- Conditions
- Leukemia, Lymphoid
- Sponsor
- Dartmouth-Hitchcock Medical Center
- Enrollment
- 20
- Locations
- 1
- Primary Endpoint
- Number of patients who are surviving at 100-Days post-transplant
- Status
- Completed
- Last Updated
- 2 years ago
Overview
Brief Summary
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.
Investigators
Kenneth Meehan
Director, Bone Marrow Transplant Program
Dartmouth-Hitchcock Medical Center
Eligibility Criteria
Inclusion Criteria
- •Age less than or equal to 75 years
- •The patient must be approved for transplant by the treating transplant physician. This includes completion of their pretransplant workup, as directed by standard Dartmouth-Hitchcock Medical Center (DHMC) Standard Operating Procedures (SOPs). DHMC SOP for Pretransplant Evaluation of allogeneic recipient.
- •The patient must have a disease, listed below, with treatment responsiveness that the treating transplant physician believes will benefit from an allogeneic stem cell transplant. The diseases include:
- •Acute leukemia AML (Acute Myeloid Leukemia), ALL (Acute Lymphoid Leukemia)
- •Chronic leukemia CML (Chronic Myeloid Leukemia), CLL (Chronic Lymphoid Leukemia)
- •Myelodysplasia
- •Myelofibrosis
- •Lymphoma NHL (Non-Hodgkin's Lymphoma) and Hodgkin's disease
- •Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia
- •Donor availability- the patient must have an identified donor
Exclusion Criteria
- •Psychiatric disorder or a mental deficiency of the patient that is sufficiently severe to make compliance with the treatment unlikely, and making informed consent impossible.
- •Major anticipated illness or organ failure incompatible with survival from bone marrow transplant.
- •History of refractory systemic infection
- •Donor eligibility
- •Human leukocyte antigen (HLA) 6 out of 6 matched related or unrelated donor.
- •The donor must be healthy and must be willing to serve as a donor, based on standard guidelines
- •The donor must have no significant comorbidities that would put the donor at marked increased risk
- •There is no age restriction for the donor
- •Informed consent must be signed by donor, if sibling donor, or by third party if unrelated donor.
- •Donor Exclusion Criteria
Arms & Interventions
Conditioning Regimen
Fludarabine, Busulfan, Rabbit ATG, Methotrexate
Intervention: Methotrexate
Conditioning Regimen
Fludarabine, Busulfan, Rabbit ATG, Methotrexate
Intervention: Rabbit ATG
Conditioning Regimen
Fludarabine, Busulfan, Rabbit ATG, Methotrexate
Intervention: Fludarabine
Conditioning Regimen
Fludarabine, Busulfan, Rabbit ATG, Methotrexate
Intervention: Busulfan
Outcomes
Primary Outcomes
Number of patients who are surviving at 100-Days post-transplant
Time Frame: 100 Days
100-Day survival of patients
Secondary Outcomes
- Time to marrow engraftment(100 Days)
- Assessing all subjects' response to treatment at 100 days post-transplant(100 Days)
- Assessing all subjects' response to treatment at 1 year post-transplant(365 Days)
- Collecting the incidents of GvHD experienced by patients post-transplant(365 Days)
- Assessing the donor-chimerism at 30, 60 and 90 days post-transplant(30, 60, and 90 Days)
- Assessing the mortality rate of patients in the first 100 days post-transplant(100 Days)
- Assessing all subjects' survival at 1 year post-transplant(365 Days)
- Assessing the number of treatment-related adverse events(365 Days)