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

Myelodysplastic Syndrome Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01295710
• Other study ID #: IV-ATG-SCT-01
• Status: Completed
• Phase: Phase 3
• Start date: October 10, 2011
• Est. completion date: October 15, 2015

Study information

• Verified date: March 2019
• Source: Neovii Biotech
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 260
• Est. completion date: October 15, 2015
• Est. primary completion date: October 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Adult Acute Lymphoid Leukemia
• Adult Acute Myeloid Leukemia
• GVHD
• Leukemia
• Leukemia, Lymphoid
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Precursor Cell Lymphoblastic Leukemia-Lymphoma
• Preleukemia
• Syndrome

Intervention

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
• Placebo
250 mL normal saline, IV infusion over 6-16 hours 3 days prior to transplantation

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Neovii Biotech

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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