## Protocol Section
### Identification Module
**NCT ID:** NCT02916979

**Acronym:** FluBuATG

**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

#### Organization Study ID Info
**ID:** D16127
#### Organization
**Class:** OTHER
**Full Name:** Dartmouth-Hitchcock Medical Center
### Status Module
#### Completion Date
**Date:** 2022-02-11

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2023-10-18

**Type:** ACTUAL

**Last Update Submit Date:** 2023-10-17

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2019-06-07

**Type:** ACTUAL

#### Start Date
**Date:** 2016-09-06

**Type:** ACTUAL

**Status Verified Date:** 2023-10

#### Study First Post Date
**Date:** 2016-09-28
**Type:** ESTIMATED
**Study First Submit Date:** 2016-08-15
**Study First Submit QC Date:** 2016-09-26
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Dartmouth-Hitchcock Medical Center

#### Responsible Party

**Investigator Affiliation:** Dartmouth-Hitchcock Medical Center

**Investigator Full Name:** Kenneth Meehan

**Investigator Title:** Director, Bone Marrow Transplant Program

**Type:** PRINCIPAL_INVESTIGATOR

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**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 Module

**Conditions:**

- Leukemia, Lymphoid

- Leukemia, Myeloid

- Myelodysplastic Syndromes

- Myelofibrosis

- Lymphoma, Malignant

- Multiple Myeloma

- Waldenstrom Macroglobulinemia

### Design Module

#### Design Info

**Allocation:** NA

**Intervention Model:** SINGLE_GROUP

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 20

**Type:** ACTUAL

**Phases:**

- PHASE1

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Fludarabine, Busulfan, Rabbit ATG, Methotrexate

**Intervention Names:**

- Drug: Fludarabine

- Drug: Busulfan

- Biological: Rabbit ATG

- Drug: Methotrexate

**Label:** Conditioning Regimen

**Type:** OTHER

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Conditioning Regimen

**Description:** Fludarabine: 30 mg/m2 daily for 5 days

**Name:** Fludarabine

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Conditioning Regimen

**Description:** Busulfan: 100 mg/m2 daily for 4 days

**Name:** Busulfan

**Type:** DRUG

#### Intervention 3

**Arm Group Labels:**

- Conditioning Regimen

**Description:** 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

**Name:** Rabbit ATG

**Type:** BIOLOGICAL

#### Intervention 4

**Arm Group Labels:**

- Conditioning Regimen

**Description:** Methotrexate:

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

**Name:** Methotrexate

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 100-Day survival of patients

**Measure:** Number of patients who are surviving at 100-Days post-transplant

**Time Frame:** 100 Days

#### Secondary Outcomes

**Description:** 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)

**Measure:** Time to marrow engraftment

**Time Frame:** 100 Days

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

**Measure:** Assessing all subjects' response to treatment at 100 days post-transplant

**Time Frame:** 100 Days

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

**Measure:** Assessing all subjects' response to treatment at 1 year post-transplant

**Time Frame:** 365 Days

**Description:** One year survival

**Measure:** Assessing all subjects' survival at 1 year post-transplant

**Time Frame:** 365 Days

**Description:** Treatment-related mortality in the first 100 days

**Measure:** Assessing the mortality rate of patients in the first 100 days post-transplant

**Time Frame:** 100 Days

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

**Measure:** Assessing the number of treatment-related adverse events

**Time Frame:** 365 Days

**Description:** Incidence of acute and chronic GVHD

**Measure:** Collecting the incidents of GvHD experienced by patients post-transplant

**Time Frame:** 365 Days

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

**Measure:** Assessing the donor-chimerism at 30, 60 and 90 days post-transplant

**Time Frame:** 30, 60, and 90 Days

### Eligibility Module

**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

**Healthy Volunteers:** True

**Maximum Age:** 75 Years

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Lebanon

**Country:** United States

**Facility:** Dartmouth-Hitchcock Medical Center

**State:** New Hampshire

**Zip:** 03756

#### Overall Officials

**Official 1:**

**Affiliation:** Dartmouth-Hitchcock Medical Center

**Name:** Kenneth Meehan, MD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**IPD Sharing:** NO

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009370

- Term: Neoplasms by Histologic Type

- ID: D000009369

- Term: Neoplasms

- ID: D000006402

- Term: Hematologic Diseases

- ID: D000054219

- Term: Neoplasms, Plasma Cell

- ID: D000020141

- Term: Hemostatic Disorders

- ID: D000014652

- Term: Vascular Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000010265

- Term: Paraproteinemias

- ID: D000001796

- Term: Blood Protein Disorders

- ID: D000006474

- Term: Hemorrhagic Disorders

- ID: D000008232

- Term: Lymphoproliferative Disorders

- ID: D000007160

- Term: Immunoproliferative Disorders

- ID: D000007154

- Term: Immune System Diseases

- ID: D000001855

- Term: Bone Marrow Diseases

- ID: D000008206

- Term: Lymphatic Diseases

### Condition Browse Module - Browse Branches

- Abbrev: BC04

- Name: Neoplasms

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: BC15

- Name: Blood and Lymph Conditions

- Abbrev: BC20

- Name: Immune System Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M12058

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: M27588

- Name: Neoplasms, Plasma Cell

- Relevance: LOW

- As Found: Unknown

- ID: M10945

- Name: Leukemia

- Relevance: HIGH

- As Found: Leukemia

- ID: M10955

- Name: Leukemia, Myeloid

- Relevance: HIGH

- As Found: Leukemia, Myeloid

- ID: M10951

- Name: Leukemia, Lymphoid

- Relevance: HIGH

- As Found: Leukemia, Lymphoid

- ID: M16355

- Name: Syndrome

- Relevance: LOW

- As Found: Unknown

- ID: M11220

- Name: Lymphoma

- Relevance: HIGH

- As Found: Lymphoma, Malignant

- ID: M14164

- Name: Preleukemia

- Relevance: LOW

- As Found: Unknown

- ID: M12145

- Name: Myelodysplastic Syndromes

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: M28312

- Name: Primary Myelofibrosis

- Relevance: LOW

- As Found: Unknown

- ID: M11251

- Name: Waldenstrom Macroglobulinemia

- Relevance: HIGH

- As Found: Waldenstrom Macroglobulinemia

- ID: M12315

- Name: Neoplasms by Histologic Type

- Relevance: LOW

- As Found: Unknown

- ID: M9490

- Name: Hematologic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M21977

- Name: Hemostatic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M5059

- Name: Blood Coagulation Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M17400

- Name: Vascular Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M13178

- Name: Paraproteinemias

- Relevance: LOW

- As Found: Unknown

- ID: M5077

- Name: Blood Protein Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M9560

- Name: Hemorrhagic Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M11225

- Name: Lymphoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10206

- Name: Immunoproliferative Disorders

- Relevance: LOW

- As Found: Unknown

- ID: M10200

- Name: Immune System Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M5134

- Name: Bone Marrow Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M11203

- Name: Lymphatic Diseases

- Relevance: LOW

- As Found: Unknown

- ID: T3947

- Name: Multiple Myeloma

- Relevance: HIGH

- As Found: Multiple Myeloma

- ID: T3543

- Name: Lymphosarcoma

- Relevance: HIGH

- As Found: Lymphoma, Malignant

- ID: T3993

- Name: Myelodysplastic Syndromes

- Relevance: HIGH

- As Found: Myelodysplastic Syndrome

- ID: T4705

- Name: Primary Myelofibrosis

- Relevance: LOW

- As Found: Unknown

- ID: T5887

- Name: Waldenstrom Macroglobulinemia

- Relevance: HIGH

- As Found: Waldenstrom Macroglobulinemia

### Condition Browse Module - Meshes

- ID: D000007938

- Term: Leukemia

- ID: D000009101

- Term: Multiple Myeloma

- ID: D000008258

- Term: Waldenstrom Macroglobulinemia

- ID: D000007951

- Term: Leukemia, Myeloid

- ID: D000007945

- Term: Leukemia, Lymphoid

- ID: D000008223

- Term: Lymphoma

- ID: D000009190

- Term: Myelodysplastic Syndromes

### Intervention Browse Module - Ancestors

- ID: D000000020

- Term: Abortifacient Agents, Nonsteroidal

- ID: D000000019

- Term: Abortifacient Agents

- ID: D000012102

- Term: Reproductive Control Agents

- ID: D000045505

- Term: Physiological Effects of Drugs

- ID: D000000964

- Term: Antimetabolites, Antineoplastic

- ID: D000000963

- Term: Antimetabolites

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000000970

- Term: Antineoplastic Agents

- ID: D000003879

- Term: Dermatologic Agents

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000005493

- Term: Folic Acid Antagonists

- ID: D000007166

- Term: Immunosuppressive Agents

- ID: D000007155

- Term: Immunologic Factors

- ID: D000018501

- Term: Antirheumatic Agents

- ID: D000019384

- Term: Nucleic Acid Synthesis Inhibitors

- ID: D000000477

- Term: Alkylating Agents

- ID: D000018906

- Term: Antineoplastic Agents, Alkylating

- ID: D000019653

- Term: Myeloablative Agonists

### Intervention Browse Module - Browse Branches

- Abbrev: ANeo

- Name: Antineoplastic Agents

- Abbrev: ARhu

- Name: Antirheumatic Agents

- Abbrev: Derm

- Name: Dermatologic Agents

- Abbrev: Repr

- Name: Reproductive Control Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Micro

- Name: Micronutrients

- Abbrev: Hemat

- Name: Hematinics

- Abbrev: Vi

- Name: Vitamins

### Intervention Browse Module - Browse Leaves

- ID: M11703

- Name: Methotrexate

- Relevance: HIGH

- As Found: Breast Cancer

- ID: M2853

- Name: Immunomodulating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M283230

- Name: Fludarabine

- Relevance: HIGH

- As Found: Comparison

- ID: M255823

- Name: Thymoglobulin

- Relevance: HIGH

- As Found: Represent

- ID: M5336

- Name: Busulfan

- Relevance: HIGH

- As Found: Full

- ID: M225513

- Name: Fludarabine phosphate

- Relevance: LOW

- As Found: Unknown

- ID: M4281

- Name: Antimetabolites

- Relevance: LOW

- As Found: Unknown

- ID: M7074

- Name: Dermatologic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M8618

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: M17546

- Name: Vitamin B Complex

- Relevance: LOW

- As Found: Unknown

- ID: M8619

- Name: Folic Acid Antagonists

- Relevance: LOW

- As Found: Unknown

- ID: M10212

- Name: Immunosuppressive Agents

- Relevance: LOW

- As Found: Unknown

- ID: M10201

- Name: Immunologic Factors

- Relevance: LOW

- As Found: Unknown

- ID: M20604

- Name: Antirheumatic Agents

- Relevance: LOW

- As Found: Unknown

- ID: M3820

- Name: Alkylating Agents

- Relevance: LOW

- As Found: Unknown

- ID: M20942

- Name: Antineoplastic Agents, Alkylating

- Relevance: LOW

- As Found: Unknown

- ID: T447

- Name: Folinic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T446

- Name: Folic Acid

- Relevance: LOW

- As Found: Unknown

- ID: T448

- Name: Folate

- Relevance: LOW

- As Found: Unknown

- ID: T475

- Name: Vitamin B9

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000008727

- Term: Methotrexate

- ID: C000024352

- Term: Fludarabine

- ID: D000002066

- Term: Busulfan

- ID: C000512542

- Term: Thymoglobulin

### Misc Info Module

- Version Holder: 2024-05-24
