A Study of Acute Graft-Versus-Host Disease (GVHD) in Patients Undergoing Allogeneic Stem-Cell Transplantation
- Registration Number
- NCT02737306
- Lead Sponsor
- CytoDyn, Inc.
- Brief Summary
This is a Phase II, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study of the Safety and Efficacy of PRO 140 for Prophylaxis of Acute Graft-Versus-Host Disease in Patients with Acute Myeloid Leukemia (AML) or Myelodysplastic Syndromes (MDS) Undergoing Allogeneic Stem-Cell Transplantation.
- Detailed Description
This is a Phase II, randomized, double-blind, placebo-controlled, multi-center study to evaluate the feasibility of the use of PRO 140 as an add-on therapy to standard GVHD prophylaxis treatment for prevention of acute GVHD in adult patients with AML or MDS undergoing allogeneic HCT.
In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e., 30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection on Day -3 or Day -2 prior to stem cell infusion, on the day of stem cell infusion (Day 0), and then weekly for 30 days (at Week 1, Week 2, Week 3 and Week 4) after which it will be administered every two weeks for up to 100±7 days (at Week 6, Week 8, Week 10, Week 12 and Week 14). Subjects will return to clinic for two Follow-up visits at 2 weeks after the last treatment visit, and one year after the first treatment visit.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 11
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e. 30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection. Placebo will be administered -2/-3 days before the stem cell infusion, on the day of stem cell infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study schedule of assessments. Each vial of the Placebo contains 5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5. Each 350 mg dose of placebo consist of 2 SC injections of placebo (5mM Histidine, 15 mM Glycine, 95 mM Sodium Chloride, 0.3% (w/v) Sorbitol, 0.005% (w/v) Polysorbate 20 at a pH of 5.5) of 2 X 1 mL/inj. on opposite sides of abdomen. 350 mg Pro140 PRO 140 In this study, 60 subjects will be randomized to receive either PRO 140 or placebo in a 1:1 ratio (i.e.,30 subjects per arm). PRO 140 or placebo will be administered as a 350 mg subcutaneous injection. PRO 140 will be administered -2/-3 days before the stem cell infusion, on the day of stem cell infusion (Day 0) and thereafter on days 7, 14, 21, 28, 42, 56, 70, 84 and 98 as per the study schedule of assessments. Each vial of the PRO 140 product contains 1.4 mL antibody at 175 mg/ml in a buffer containing 5 mM L-histidine, 15.0 mM glycine, 95 mM sodium chloride, 0.3% (w/v) sorbitol, 0.005% (w/v) polysorbate 20 (Tween 20®), and sterile water for injection, at pH of 5.5. Each 350 mg dose of PRO 140 will consist of 2 SC injections of PRO 140 (2 X 1 mL/inj.) on opposite sides of abdomen.
- Primary Outcome Measures
Name Time Method Incidence of Acute GVHD by Day 100 100 days from first treatment (100 Days post treatment) Incidence of Grade II, Grade III or Grade IV acute GVHD by Day-100
- Secondary Outcome Measures
Name Time Method Changes and Shifts in Laboratory Measurements Over Time 365 days post-treatment (+/- 14 days) Safety Assessment- The laboratory measurements will include Routine CBC, Biochemistry and Urinalysis.
* Routine CBC includes hemoglobin, hematocrit (HCT), red blood cell (RBC) count, white blood cell (WBC) count, WBC differential count (%), absolute neutrophils count (ANC) and platelets count.
* Biochemistry profile includes assessment of Hepatic function indicators: total and direct bilirubin, alkaline phosphatase (ALP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein, Lactate dehydrogenase (LDH); Renal function indicators: Blood Urea Nitrogen (BUN), creatinine; Electrolytes: sodium, potassium, chloride, calcium and bicarbonate; Other: glucose (random), cholesterol (total)
* Urinalysis for color, appearance, specific gravity, pH, protein, glucose, occult blood, ketones, RBC, WBC, epithelial cells, bacteria, casts, crystalsIncidence of Organ-specific Acute GVHD by Day-100 100 Days post-treatment The number and percentages of subjects with organ-specific acute GVHD by Day-100 will be presented by organ category. Chi-square/ Fisher's exact test will be used to compare the incidence between the treatment groups.
Frequency of Treatment Emergent Adverse Events and Serious Adverse Events 100 Days post treatment Frequency of treatment emergent adverse events and treatment emergent serious adverse events.
AML or MDS Relapse Rate by Day-100 100 Days post treatment AML or MDS relapse rate by Day-100 will be summarized and present by treatment groups.
Incidence of Severe and Life-threatening (Grade III and Grade IV) Acute GVHD by Day-100 100 Days post-treatment The number and percentages of subjects with severe and life-threatening (Grade III and Grade IV) acute GVHD by Day-100 will be presented. Chi-square/ Fisher's exact test will be used to compare the incidence between the treatment groups.
GVHD-free Survival (GFS) 100 Days post treatment visit T1 GFS will be defined as the elapsed time between the date of transplant until GVHD related death. GVHD-free survival will be compared between the treatment groups using Log-rank test and Kaplan-Meier methods will be used to depict the survival curves.
Tolerability of Repeated Subcutaneous Administration of PRO 140 as Assessed by Study Participants (Using Visual Analogue Scale) and by Investigator-evaluation of Injection Site Reactions 365 days post-treatment (+/- 14 days) All data from tolerability assessments of repeated subcutaneous administration of PRO 140 as assessed by study participants and by investigator-evaluation of injection site reactions will be summarized using n, mean, Standard Deviation (SD), minimum and maximum values.
Neutrophil and Platelet Count Recovery 100 Days post treatment The number and percentages of subjects with neutrophil and platelet count recovery will be presented. Chi-square/ Fisher's exact test will be used to compare the incidence of neutrophil recovery and of platelet recovery between treatment groups.
Donor Engraftment Evaluated by T-cell and Myeloid Chimerism in Peripheral Blood 365 days post-initial treatment (T1 Visit) (+/- 14 days) The number and percentages of subjects with donor engraftment failure evaluated by T-cell and myeloid chimerism in peripheral blood will be presented by different treatment groups. Chi-square/ Fisher's exact test will be used to compare the incidence of donor engraftment failure.
Changes in ECOG Performance Score 100 Days post treatment visit 1 The raw and change from baseline in ECOG performance score will be summarized for each assessment scheduled visit (i.e., Screening visit, Treatment Visits 1, 4, 7, 9, 11, Follow-up Visit 1and Unscheduled Visit(s)). Descriptive statistics (n, mean, standard deviation, median, minimum and maximum) will be presented by treatment group. If the Normality assumption is met, t-test will be used to compare the mean of ECOG performance score between the treatment groups and if the Normality assumption is not met, a non-parametric method will be used.
Changes in Electrocardiogram (ECG) Parameters Over Time 365 days post-treatment (+/- 14 days) Safety Assessment-The following ECG parameters will be evaluated: ventricular rate (beats per minute), PR interval (msec), QRS interval (msec), QT interval (msec), and QTc interval (msec).
Trial Locations
- Locations (8)
University of Miami Sylvester Comprehensive Cancer Center
🇺🇸Miami, Florida, United States
Loyola University Medical Center Cardinal Bernardin Cancer Center
🇺🇸Maywood, Illinois, United States
West Virginia University Medicine
🇺🇸Morgantown, West Virginia, United States
Barbara Ann Karmanos Cancer Institute
🇺🇸Detroit, Michigan, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Texas Transplant Institute Methodist Hospital
🇺🇸San Antonio, Texas, United States
Wake Forest Baptist Health
🇺🇸Winston-Salem, North Carolina, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States