Myeloid-Derived Suppressor Cells and Checkpoint Immune Regulators' Expression in Allogeneic SCT Using FluBuATG

Sponsor
Dartmouth-Hitchcock Medical Center (Other)
Overall Status
Active, not recruiting
CT.gov ID
NCT02916979
Collaborator
(none)
20
Enrollment
1
Location
1
Arm
64
Duration (Months)
0.3
Patients Per Site Per Month

Study Details

Study Description

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 Design

Study Type:
Interventional
Actual Enrollment :
20 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
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
Study Start Date :
Aug 1, 2016
Actual Primary Completion Date :
Dec 1, 2020
Anticipated Study Completion Date :
Dec 1, 2021

Arms and Interventions

ArmIntervention/Treatment
Other: Conditioning Regimen

Fludarabine, Busulfan, Rabbit ATG, Methotrexate

Drug: Fludarabine
Fludarabine: 30 mg/m2 daily for 5 days

Drug: Busulfan
Busulfan: 100 mg/m2 daily for 4 days

Biological: Rabbit ATG
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

Drug: Methotrexate
Methotrexate: Related donors: 5 mg/m2 on days 1, 3 and 6 Unrelated donors: 5 mg/m2 on days 1, 3, 6 and 11

Outcome Measures

Primary Outcome Measures

  1. Number of patients who are surviving at 100-Days post-transplant [100 Days]

    100-Day survival of patients

Secondary Outcome Measures

  1. Time to marrow engraftment [100 Days]

    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)

  2. Assessing all subjects' response to treatment at 100 days post-transplant [100 Days]

    Response to treatment at 100 days using standard international response criteria, based on CIBMTR definitions.

  3. Assessing all subjects' response to treatment at 1 year post-transplant [365 Days]

    Response to treatment at one year using standard international response criteria, based on CIBMTR definitions.

  4. Assessing all subjects' survival at 1 year post-transplant [365 Days]

    One year survival

  5. Assessing the mortality rate of patients in the first 100 days post-transplant [100 Days]

    Treatment-related mortality in the first 100 days

  6. Assessing the number of treatment-related adverse events [365 Days]

    Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  7. Collecting the incidents of GvHD experienced by patients post-transplant [365 Days]

    Incidence of acute and chronic GVHD

  8. Assessing the donor-chimerism at 30, 60 and 90 days post-transplant [30, 60, and 90 Days]

    Donor-recipient chimerism following transplant at Days 30, 60 and 90.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
Yes
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:

  4. Acute leukemia AML (Acute Myeloid Leukemia), ALL (Acute Lymphoid Leukemia)

  5. Chronic leukemia CML (Chronic Myeloid Leukemia), CLL (Chronic Lymphoid Leukemia)

  6. Myelodysplasia

  7. Myelofibrosis

  8. Lymphoma NHL (Non-Hodgkin's Lymphoma) and Hodgkin's disease

  9. Plasma cell disorder, including myeloma, Waldenstrom's Macroglobulinemia

  10. Donor availability- the patient must have an identified donor

  11. Sibling Availability of a 6 out of 6 identical donor

  12. Unrelated donor: Availability of a 6 out of 6 unrelated donor

  13. No human immunodeficiency virus (HIV) infection or active hepatitis B or C

  14. Easter Cooperative Oncology Group (ECOG) performance status 0, 1, or 2

  15. Diffusing capacity of the lungs for carbon monoxide DLCO more than or equal to 40 percent predicted

  16. Left ventricular ejection fraction more than or equal to 35 percent

  17. Serum bilirubin less than 2x upper limit of normal transaminases less than 3x normal at the time of transplant

  18. No active or uncontrollable infection

  19. In female, a negative pregnancy test if experiencing menstrual periods

  20. No major organ dysfunction precluding transplantation

  21. 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

  1. The National Marrow Donor Program (NMDP) guidelines for exclusion criteria will be used. In addition, the following donors are NOT eligible:

  2. Syngeneic donor

  3. Pregnant or lactating donor

  4. Human immunodeficiency virus (HIV) or active HepB or C in the donor

  5. Donor unfit to receive Granulocyte-colony stimulating factor (GCSF) and undergo apheresis

  6. A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Dartmouth-Hitchcock Medical CenterLebanonNew HampshireUnited States03756

Sponsors and Collaborators

  • Dartmouth-Hitchcock Medical Center

Investigators

  • Principal Investigator: Kenneth Meehan, MD, Dartmouth-Hitchcock Medical Center

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Kenneth Meehan, Director, Bone Marrow Transplant Program, Dartmouth-Hitchcock Medical Center
ClinicalTrials.gov Identifier:
NCT02916979
Other Study ID Numbers:
  • D16127
First Posted:
Sep 28, 2016
Last Update Posted:
Feb 1, 2021
Last Verified:
Jan 1, 2021

Study Results

No Results Posted as of Feb 1, 2021