Brief Title
Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG
Official Title
A Pilot Trial Examining Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic Stem Cell Transplant Recipients Using Myeloablative Busulfan and Fludarabine
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.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
Number of patients who are surviving at 100-Days post-transplant
Secondary Outcome
Time to marrow engraftment
Condition
Leukemia, Lymphoid
Intervention
Fludarabine
Study Arms / Comparison Groups
Conditioning Regimen
Description: Fludarabine, Busulfan, Rabbit ATG, Methotrexate
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
September 6, 2016
Completion Date
June 2022
Primary Completion Date
December 2020
Eligibility Criteria
Inclusion Criteria:
1. Age less than or equal to 75 years
2. 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.
3. 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:
1. Acute leukemia AML (Acute Myeloid Leukemia), ALL (Acute Lymphoid Leukemia)
2. Chronic leukemia CML (Chronic Myeloid Leukemia), CLL (Chronic Lymphoid Leukemia)
3. Myelodysplasia
4. Myelofibrosis
5. Lymphoma NHL (Non-Hodgkin's Lymphoma) and Hodgkin's disease
6. Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia
4. Donor availability- the patient must have an identified donor
1. Sibling Availability of a 6 out of 6 identical donor
2. Unrelated donor: Availability of a 6 out of 6 unrelated donor
5. No human immunodeficiency virus (HIV) infection or active hepatitis B or C
6. Easter Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
7. Diffusing capacity of the lungs for carbon monoxide DLCO more than or equal to 40
percent predicted
8. Left ventricular ejection fraction more than or equal to 35 percent
9. Serum bilirubin less than 2x upper limit of normal transaminases less than 3x normal
at the time of transplant
10. No active or uncontrollable infection
11. In female, a negative pregnancy test if experiencing menstrual periods
12. No major organ dysfunction precluding transplantation
13. No evidence of an active malignancy that would limit the patient's survival to less
than 2 years. If there is any question, the principal investigator can make a
decision.
Exclusion Criteria:
1. 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.
2. Major anticipated illness or organ failure incompatible with survival from bone marrow
transplant.
3. History of refractory systemic infection
Donor eligibility
1. Human leukocyte antigen (HLA) 6 out of 6 matched related or unrelated donor.
2. The donor must be healthy and must be willing to serve as a donor, based on standard
guidelines
3. The donor must have no significant comorbidities that would put the donor at marked
increased risk
4. There is no age restriction for the donor
5. Informed consent must be signed by donor, if sibling donor, or by third party if
unrelated donor.
Donor Exclusion Criteria
6. The National Marrow Donor Program (NMDP) guidelines for exclusion criteria will be
used. In addition, the following donors are NOT eligible:
7. Syngeneic donor
8. Pregnant or lactating donor
9. Human immunodeficiency virus (HIV) or active HepB or C in the donor
10. Donor unfit to receive Granulocyte-colony stimulating factor (GCSF) and undergo
apheresis
11. A donor with a psychiatric disorder or mental deficiency that makes compliance with
the procedure unlikely and informed consent impossible
Gender
All
Ages
18 Years - 75 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Contacts
Kenneth Meehan, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT02916979
Organization ID
D16127
Responsible Party
Principal Investigator
Study Sponsor
Dartmouth-Hitchcock Medical Center
Study Sponsor
Kenneth Meehan, MD, Principal Investigator, Dartmouth-Hitchcock Medical Center
Verification Date
April 2022