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

NCT02916979 | Completed Phase 1 DMC

• 1 other identifier: D16127
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Leukemia, Lymphoid; Leukemia, Myeloid; Myelodysplastic Syndromes; Myelofibrosis; Lymphoma, Malignant; Multiple Myeloma; Waldenstrom Macroglobulinemia

Outcome Measures

Primary Outcomes (1)

• Number of patients who are surviving at 100-Days post-transplant

  100-Day survival of patients

  100 Days

Secondary Outcomes (8)

• 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

• Assessing all subjects' survival at 1 year post-transplant

  365 Days

• Assessing the mortality rate of patients in the first 100 days post-transplant

  100 Days

Study Arms (1)

Conditioning Regimen

OTHER

Fludarabine, Busulfan, Rabbit ATG, Methotrexate

Drug: Fludarabine; Drug: Busulfan; Biological: Rabbit ATG; Drug: Methotrexate

Interventions

Fludarabine DRUG

Fludarabine: 30 mg/m2 daily for 5 days

Conditioning Regimen

Busulfan DRUG

Busulfan: 100 mg/m2 daily for 4 days

Conditioning Regimen

Rabbit ATG BIOLOGICAL

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

Conditioning Regimen

Methotrexate DRUG

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

Conditioning Regimen

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Sibling Availability of a 6 out of 6 identical donor
• Unrelated donor: Availability of a 6 out of 6 unrelated donor
• No human immunodeficiency virus (HIV) infection or active hepatitis B or C
• Easter Cooperative Oncology Group (ECOG) performance status 0, 1, or 2
• Diffusing capacity of the lungs for carbon monoxide DLCO more than or equal to 40 percent predicted

You may not qualify if:

• 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.
• Syngeneic donor
• Pregnant or lactating donor
• Human immunodeficiency virus (HIV) or active HepB or C in the donor
• Donor unfit to receive Granulocyte-colony stimulating factor (GCSF) and undergo apheresis
• A donor with a psychiatric disorder or mental deficiency that makes compliance with the procedure unlikely and informed consent impossible

Sponsors & Collaborators

• Dartmouth-Hitchcock Medical Center: lead

Study Sites (1)

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, 03756, United States

Location

MeSH Terms

Conditions

Leukemia, Lymphoid; Leukemia, Myeloid; Myelodysplastic Syndromes; Primary Myelofibrosis; Lymphoma; Multiple Myeloma; Waldenstrom Macroglobulinemia

Interventions

fludarabine; Busulfan; thymoglobulin; Methotrexate

Condition Hierarchy (Ancestors)

Leukemia; Neoplasms by Histologic Type; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases; Bone Marrow Diseases; Myeloproliferative Disorders; Neoplasms, Plasma Cell; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Butylene Glycols; Glycols; Alcohols; Organic Chemicals; Mesylates; Alkanesulfonates; Alkanesulfonic Acids; Alkanes; Hydrocarbons, Acyclic; Hydrocarbons; Sulfonic Acids; Sulfur Acids; Sulfur Compounds; Aminopterin; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kenneth Meehan, MD

  Dartmouth-Hitchcock Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bone Marrow Transplant Program

Study Record Dates

• First Submitted: August 15, 2016
• First Posted: September 28, 2016
• Study Start: September 6, 2016
• Primary Completion: June 7, 2019
• Study Completion: February 11, 2022
• Last Updated: October 18, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)