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

Phase 3

Completed

Conditions: Adult Acute Myeloid Leukemia
Adult Acute Lymphoid Leukemia
Myelodysplastic Syndrome
GVHD

Interventions: Biological: US-ATG-F
Biological: Placebo

Registration Number: NCT01295710

Lead Sponsor: Neovii Biotech

Brief Summary: 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.

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 260

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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
US-ATG-F	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
Placebo	Placebo	250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation

Primary Outcome Measures

Name	Time	Method
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	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	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

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Acute GVHD Grade III-IV	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	Participants with the first occurrence of acute GVHD grade III-IV as determined by the Investigators, with death and re transplantation as competing risks
Number of Participants With Relapse	Time from first study drug administration until the occurrence of relapse, with death as competing risk, assessed up to 48 months	Participants with relapse or disease recurrence, with death as competing risk
Number of Participants With Transplant Related Mortality	Time from first study drug administration until the occurrence of transplant related mortality, assessed up to 48 months	Participants with transplant related mortality
Systemic Immunosuppressive Medication for Treatment of Moderate to Severe Chronic GVHD	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	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
Overall Survival	Time from first study drug administration until the occurrence of death from any cause, assessed up to 48 months	Incidence of death from any cause
Number of Participants With Chronic GVHD Mild to Severe	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	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
Number of Participants With Chronic GVHD Moderate to Severe	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	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
Number of Participants With Chronic GVHD Severe	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	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
Number of Participants With Acute GVHD Grade I-IV	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	Participants with the first occurrence of acute GVHD grade I-IV as determined by the Investigators, with death and re transplantation as competing risks
Number of Participants With Acute GVHD Grade II-IV	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	Participants with the first occurrence of acute GVHD grade II-IV as determined by the Investigators, with death and re transplantation as competing risks
Disease-free Survival	Time from first study drug administration until the occurrence of relapse or death, assessed up to 48 months	Incidence of relapse or death

Trial Locations

Locations (28): City of Hope
🇺🇸
Duarte, California, United States
University of Florida Shands Cancer Center
🇺🇸
Gainesville, Florida, United States
Stanford University Medical Center, BMT
🇺🇸
Stanford, California, United States
Loyola University Medical Center
🇺🇸
Maywood, Illinois, United States
Washington University Medical Center
🇺🇸
Saint Louis, Missouri, United States
Weill Cornell Medical Center
🇺🇸
New York, New York, United States
Royal Adelaide Hospital
🇦🇺
Adelaide, South Australia, Australia
University of North Carolina Hospitals
🇺🇸
Chapel Hill, North Carolina, United States
University of Chicago Medical Center
🇺🇸
Chicago, Illinois, United States
Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Beth Israel Deaconess Medical Center
🇺🇸
Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸
Boston, Massachusetts, United States
Duke University Medical Center
🇺🇸
Durham, North Carolina, United States
University of Oklahoma Health Sciences Center
🇺🇸
Oklahoma City, Oklahoma, United States
Oregon Health and Science University
🇺🇸
Portland, Oregon, United States
Abramson Cancer Center of the University at Perlman Center for Advanced Medicine
🇺🇸
Philadelphia, Pennsylvania, United States
Texas Transplant Physician's Group
🇺🇸
San Antonio, Texas, United States
VA Puget Sound Healthcare System
🇺🇸
Seattle, Washington, United States
Vanderbilt University Medical Center, Vanderbilt Ingram Cancer Center
🇺🇸
Nashville, Tennessee, United States
University of Texas Southwestern Medical Center
🇺🇸
Dallas, Texas, United States
University of Utah School of Medicine
🇺🇸
Salt Lake City, Utah, United States
Fred Hutchinson Cancer Research Center
🇺🇸
Seattle, Washington, United States
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Mayo Clinic
🇺🇸
Rochester, Minnesota, United States
Tulane University Health Sciences Center
🇺🇸
New Orleans, Louisiana, United States
Penn State Hershey Cancer Institute
🇺🇸
Hershey, Pennsylvania, United States
Royal Melbourne Hospital
🇦🇺
Parkville, Victoria, Australia
University of Kansas Medical Center
🇺🇸
Westwood, Kansas, United States