A Phase II, Randomized, Double-Blind, Placebo-Controlled 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)
Overview
- Phase
- Phase 2
- Intervention
- Placebo
- Conditions
- Graft Vs Host Disease
- Sponsor
- CytoDyn, Inc.
- Enrollment
- 11
- Locations
- 8
- Primary Endpoint
- Incidence of Acute GVHD by Day 100
- Status
- Terminated
- Last Updated
- 2 years ago
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
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.
Intervention: Placebo
350 mg Pro140
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.
Intervention: PRO 140
Outcomes
Primary Outcomes
Incidence of Acute GVHD by Day 100
Time Frame: 100 days from first treatment (100 Days post treatment)
Incidence of Grade II, Grade III or Grade IV acute GVHD by Day-100
Secondary Outcomes
- Changes and Shifts in Laboratory Measurements Over Time(365 days post-treatment (+/- 14 days))
- Incidence of Organ-specific Acute GVHD by Day-100(100 Days post-treatment)
- Frequency of Treatment Emergent Adverse Events and Serious Adverse Events(100 Days post treatment)
- AML or MDS Relapse Rate by Day-100(100 Days post treatment)
- GVHD-free Survival (GFS)(100 Days post treatment visit T1)
- Incidence of Severe and Life-threatening (Grade III and Grade IV) Acute GVHD by Day-100(100 Days post-treatment)
- 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))
- Neutrophil and Platelet Count Recovery(100 Days post treatment)
- Donor Engraftment Evaluated by T-cell and Myeloid Chimerism in Peripheral Blood(365 days post-initial treatment (T1 Visit) (+/- 14 days))
- Changes in ECOG Performance Score(100 Days post treatment visit 1)
- Changes in Electrocardiogram (ECG) Parameters Over Time(365 days post-treatment (+/- 14 days))