Study of US-ATG-F to Prevent Chronic Graft Versus Host Disease (GVHD)

Phase 3 Study of US-ATG-F to Prevent Moderate to Severe Chronic GVHD in Adult Acute Myeloid Leukemia, Acute Lymphoid Leukemia, and Myelodysplastic Syndrome Patients After Allogeneic Stem Cell Transplantation From Unrelated Donors

The study objective is to compare the efficacy and safety of US-ATG-F as a supplement to standard of care prophylaxis versus standard of care prophylaxis alone in moderate to severe chronic GVHD-free survival.

Study Overview

• Status: Completed
• Conditions: Myelodysplastic Syndrome; GVHD; Adult Acute Myeloid Leukemia; Adult Acute Lymphoid Leukemia
• Intervention / Treatment: Biological: US-ATG-F; Biological: Placebo

Detailed Description

This study is randomized, prospective, double-blind, placebo-controlled, phase 3 study evaluating the prevention of moderate to severe chronic GVHD in patients undergoing bone marrow or peripheral blood stem cell transplantation from matched, unrelated donors for acute leukemia and myelodysplastic syndrome during the first year after transplant.

Patients meeting all the inclusion and none of the exclusion criteria will be randomized (1:1). All patients will receive premedication and study drug 3 days prior to transplantation.

• Study Type: Interventional
• Enrollment (Actual): 260
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • South Australia
    • Adelaide, South Australia, Australia, 5000
      • Royal Adelaide Hospital
  • Victoria
    • Parkville, Victoria, Australia, 03050
      • Royal Melbourne Hospital
• United States
  • California
    • Duarte, California, United States, 91019
      • City of Hope
    • Stanford, California, United States, 94305
      • Stanford University Medical Center, BMT
  • Florida
    • Gainesville, Florida, United States, 32610
      • University of Florida Shands Cancer Center
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
    • Maywood, Illinois, United States, 60153
      • Loyola University Medical Center
  • Kansas
    • Westwood, Kansas, United States, 66205
      • University of Kansas Medical Center
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University Health Sciences Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
    • Boston, Massachusetts, United States, 02215
      • Dana-Farber Cancer Institute
    • Boston, Massachusetts, United States, 02215
      • Massachusetts General Hospital
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University Medical Center
  • New York
    • New York, New York, United States, 10065
      • Weill Cornell Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina Hospitals
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma Health Sciences Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health and Science University
  • Pennsylvania
    • Hershey, Pennsylvania, United States, 17033
      • Penn State Hershey Cancer Institute
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center of the University at Perlman Center for Advanced Medicine
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center, Vanderbilt Ingram Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • San Antonio, Texas, United States, 78229
      • Texas Transplant Physician'S Group
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah School of Medicine
  • Washington
    • Seattle, Washington, United States, 98109
      • Fred Hutchinson Cancer Research Center
    • Seattle, Washington, United States, 98108
      • VA Puget Sound Healthcare System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Key Inclusion Criteria:

• Patients designated to undergo allogeneic peripheral blood or bone marrow stem cell transplantation following the diagnosis of one of the primary diseases in early or intermediate disease status (i.e., acute myeloid leukemia, acute lymphoid leukemia, and myelodysplastic syndrome)
• Patients with an unrelated HLA-A,-B, -C and -DRBI matched donor
• Patients with a Karnofsky Performance Score ≥ 70%

Key Exclusion Criteria:

• Clinically significant concomitant diseases (i.e., cardiac, pulmonary, renal and CNS)
• Bacterial, viral, or fungal infections
• Known positive for Hepatitis B surfaces antigen, or Hepatitis C antibody, or who have been tested positive for HIV
• Patients with any concurrent malignancy. Cancer treated with curative intent < 5 years previously will not be allowed except for patients with resected basal cell carcinoma or treated cervical carcinoma in situ
• Known contraindications to the administration of rabbit immunoglobulin antibodies
• Hypersensitivity to methylprednisolone, tacrolimus, methotrexate or any excipients contains in these products

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: US-ATG-F; 20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	Biological: US-ATG-F; 20 mg/kg body weight per day, diluted in 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation; Other Names: Anti-human-T-lymphocyte Immune Globulin, Rabbit
Placebo Comparator: Placebo; 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation	Biological: Placebo; 250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With First Occurrence of Moderate to Severe Chronic GVHD According to 2005 NIH Criteria as Determined by the Independent Endpoint Committee or Death From Any Cause After Allogeneic Stem Cell Transplantation	Participants with first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee or death from any cause after allogeneic stem cell transplantation, with a target of 124 total events of moderate or severe chronic GVHD, or death from any cause	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Independent Endpoint Committee, or death from any cause, assessed up to 48 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival	Incidence of death from any cause	Time from first study drug administration until the occurrence of death from any cause, assessed up to 48 months
Number of Participants With Chronic GVHD Mild to Severe	Participants with the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks	Time from first study drug administration until the first occurrence of mild to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months
Number of Participants With Chronic GVHD Moderate to Severe	Participants with the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks	Time from first study drug administration until the first occurrence of moderate to severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months
Number of Participants With Chronic GVHD Severe	Participants with the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks	Time from first study drug administration until the first occurrence of severe chronic GVHD according to 2005 NIH criteria as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months
Number of Participants With Acute GVHD Grade I-IV	Participants with the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks	Time from first study drug administration until the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months
Number of Participants With Acute GVHD Grade II-IV	Participants with the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks	Time from first study drug administration until the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months
Number of Participants With Acute GVHD Grade III-IV	Participants with the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks	Time from first study drug administration until the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks, assessed up to 48 months
Number of Participants With Relapse	Participants with relapse or disease recurrence, with death as competing risk	Time from first study drug administration until the occurrence of relapse, with death as competing risk, assessed up to 48 months
Disease-free Survival	Incidence of relapse or death	Time from first study drug administration until the occurrence of relapse or death, assessed up to 48 months
Number of Participants With Transplant Related Mortality	Participants with transplant related mortality	Time from first study drug administration until the occurrence of transplant related mortality, assessed up to 48 months
Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD	Participants who started on systemic immunosuppressive medicine for treatment of moderate to severe chronic GVHD as determined by the Investigator, with death and re-transplantation as competing risks	Time from first study drug administration until start of systemic immunosuppressive medicine for treatment of moderate to severe chronic GVHD as determined by the Investigator, with death and re-transplantation as competing risks, assessed up to 48 months

Collaborators and Investigators

• Sponsor: Neovii Biotech
• Investigators: Study Director: Anne Kuan, Neovii Biotech

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2011
• Primary Completion (Actual): October 15, 2015
• Study Completion (Actual): October 15, 2015

Study Registration Dates

• First Submitted: February 9, 2011
• First Submitted That Met QC Criteria: February 11, 2011
• First Posted (Estimate): February 14, 2011

Study Record Updates

• Last Update Posted (Actual): April 9, 2019
• Last Update Submitted That Met QC Criteria: March 29, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: GVHD; adult acute myeloid leukemia; unrelated donor; allogenic stem cell transplantation; adult acute lymphoid leukemia; adult myelodysplastic syndrome; US-ATG-F (Anti-human-T-lymphocyte Immune Globulin, Rabbit)
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Leukemia, Lymphoid; Physiological Effects of Drugs; Immunosuppressive Agents; Immunologic Factors; Immunoglobulins; Antilymphocyte Serum
• Other Study ID Numbers: IV-ATG-SCT-01