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

NCT ID: NCT02916979

Last Updated: 2023-10-18

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-06
• Study Completion Date: 2022-02-11

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Conditioning Regimen

Fludarabine, Busulfan, Rabbit ATG, Methotrexate

Group Type: OTHER

Fludarabine

Intervention Type: DRUG

Fludarabine: 30 mg/m2 daily for 5 days

Busulfan

Intervention Type: DRUG

Busulfan: 100 mg/m2 daily for 4 days

Rabbit ATG

Intervention Type: 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

Methotrexate

Intervention Type: 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

Interventions

Fludarabine

Fludarabine: 30 mg/m2 daily for 5 days

Intervention Type: DRUG

Busulfan

Busulfan: 100 mg/m2 daily for 4 days

Intervention Type: DRUG

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

Intervention Type: BIOLOGICAL

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

Intervention Type: DRUG

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.

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Dartmouth-Hitchcock Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Kenneth Meehan

Director, Bone Marrow Transplant Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Kenneth Meehan, MD

Role: PRINCIPAL_INVESTIGATOR

Dartmouth-Hitchcock Medical Center

Locations

Dartmouth-Hitchcock Medical Center

Lebanon, New Hampshire, United States

Countries

United States

Other Identifiers

D16127

Identifier Type: -

Identifier Source: org_study_id