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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

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

Intervention / Treatment
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* Biological: US-ATG-F
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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adult acute myeloid leukemia, adult acute lymphoid leukemia, adult myelodysplastic syndrome, allogenic stem cell transplantation, unrelated donor, GVHD, US-ATG-F (Anti-human-T-lymphocyte Immune Globulin, Rabbit)