First-line risk-adapted treatment trials for aGVHD
| Study number . | GVHD risk category . | Study type/intervention . | Treatment target . | Transplant eligibility criteria . | Study status . | Primary outcome measures . |
|---|---|---|---|---|---|---|
| Standard-risk aGVHD | ||||||
| NCT02806947 BMT CTN 1501(19) | Standard-risk (Minnesota risk), previously untreated aGVHD requiring systemic therapy, AA score 1-2 biomarker assessment (performed at randomization) | Randomized, multicenter, phase 2 Sirolimus vs prednisone 2 mg/kg | mTOR inhibitor | Any donor type, conditioning Child, adult, older-adult ages | Completed | Day-28 CR/PR rates similar for sirolimus vs prednisone (64.8% vs 73%) Sirolimus associated with reduced steroid exposure and hyperglycemia, improved QOL, and increased risk for TMA |
| NCT03846479 | Low-risk aGVHD, Minnesota standard risk, AA score 1 | Single arm, monotherapy Itacitinib | JAK1 inhibitor | Any donor type, conditioning Ages 12-75 years | Recruiting | Day-28 Minnesota standard-risk clinical criteria (CR, PR, TRM) Day-28 AA score 1 |
| NCT04144036 | Standard-risk aGVHD, Minnesota risk, AA score 1-2 | Single-center nonrandomized phase 1 Neihulizumab dose escalation | Humanized monoclonal antibody binding to CD162 (PSGL-1) | Any donor type, conditioning Ages ≥18 years | Recruiting | Day-28 SAE, MTD of neihulizumab, plasma Cmax |
| High-risk aGVHD | ||||||
| NCT02133924 | High-risk aGVHD, AA score 3 | Multicenter, phase 2 Natalizumab + prednisone | Humanized recombinant antibody binding to alpha-4 integrin | Any donor type, conditioning Ages ≥18 years | Recruiting | Day-28 CR |
| NCT0252502917 | Arm 1: high-risk aGVHD (Minnesota risk, or AA score 3, or AREG ≥33 pg/mL) Arm 2a: steroid-dependent aGVHD Arm 2b: SR-aGVHD | Nonrandomized phase ½ Standard of care IST + Pregnyl | uhCG, which may promote immune tolerance, provides source of EGF for epithelial repair (Pregnyl®) | Any donor type, conditioning Ages 0-76 years | Active, not recruiting | Phase 1: MTD of uhCG/EGF in combination with standard IST Phase 2: day-28 CR, PR, MR, and no response |
| NCT03158896 | De novo high-risk aGVHD SR-aGVHD | Phase 1, dose escalation Umbilical cord-derived, ex vivo cultured, and expanded Wharton's Jelly MSC | Immunosuppressive properties: suppress proliferation of activated T cells, increase production of regulatory T cells, shift immune response toward tolerance | Ages 18-75 years | Active, not recruiting | Day-45 treatment-related SAE |
| NCT04061876 | High-risk grade 2-4 aGVHD (based on ST2, REG3α, or other experiment object) | Randomized, phase 2 Ruxolitinib + corticosteroids vs corticosteroids alone | JAK1/2 inhibitor | Any donor type Ages 14-65 years | Recruiting | Day-28 ORR |
| NCT04167514 | High-risk aGVHD requiring corticosteroids (first-line therapy) | Randomized, double-blind, placebo-controlled, multicenter phase 3 AAT + corticosteroids vs corticosteroids alone | Serine protease inhibitor | Any donor type, conditioning Ages ≥18 years | Recruiting | Day-28 CR, PR |
| NCT04291261 | High-risk aGVHD, AA score 2-3 | Single-arm phase 2 ECP with methoxsalen +2 mg/kg corticosteroids | Induces apoptosis of mononuclear cells | Any donor type, conditioning Ages ≥18 years | Active, not recruiting | Day-28 CR |
| NCT04397367 | Grade 2-4 or high-risk aGVHD (based on ST2, REG3α, or other experiment object) | Nonrandomized Ruxolitinib + corticosteroids | JAK1/2 inhibitor | Any donor type Ages 14-65 years | Recruiting | Day-28 CR |
| Study number . | GVHD risk category . | Study type/intervention . | Treatment target . | Transplant eligibility criteria . | Study status . | Primary outcome measures . |
|---|---|---|---|---|---|---|
| Standard-risk aGVHD | ||||||
| NCT02806947 BMT CTN 1501(19) | Standard-risk (Minnesota risk), previously untreated aGVHD requiring systemic therapy, AA score 1-2 biomarker assessment (performed at randomization) | Randomized, multicenter, phase 2 Sirolimus vs prednisone 2 mg/kg | mTOR inhibitor | Any donor type, conditioning Child, adult, older-adult ages | Completed | Day-28 CR/PR rates similar for sirolimus vs prednisone (64.8% vs 73%) Sirolimus associated with reduced steroid exposure and hyperglycemia, improved QOL, and increased risk for TMA |
| NCT03846479 | Low-risk aGVHD, Minnesota standard risk, AA score 1 | Single arm, monotherapy Itacitinib | JAK1 inhibitor | Any donor type, conditioning Ages 12-75 years | Recruiting | Day-28 Minnesota standard-risk clinical criteria (CR, PR, TRM) Day-28 AA score 1 |
| NCT04144036 | Standard-risk aGVHD, Minnesota risk, AA score 1-2 | Single-center nonrandomized phase 1 Neihulizumab dose escalation | Humanized monoclonal antibody binding to CD162 (PSGL-1) | Any donor type, conditioning Ages ≥18 years | Recruiting | Day-28 SAE, MTD of neihulizumab, plasma Cmax |
| High-risk aGVHD | ||||||
| NCT02133924 | High-risk aGVHD, AA score 3 | Multicenter, phase 2 Natalizumab + prednisone | Humanized recombinant antibody binding to alpha-4 integrin | Any donor type, conditioning Ages ≥18 years | Recruiting | Day-28 CR |
| NCT0252502917 | Arm 1: high-risk aGVHD (Minnesota risk, or AA score 3, or AREG ≥33 pg/mL) Arm 2a: steroid-dependent aGVHD Arm 2b: SR-aGVHD | Nonrandomized phase ½ Standard of care IST + Pregnyl | uhCG, which may promote immune tolerance, provides source of EGF for epithelial repair (Pregnyl®) | Any donor type, conditioning Ages 0-76 years | Active, not recruiting | Phase 1: MTD of uhCG/EGF in combination with standard IST Phase 2: day-28 CR, PR, MR, and no response |
| NCT03158896 | De novo high-risk aGVHD SR-aGVHD | Phase 1, dose escalation Umbilical cord-derived, ex vivo cultured, and expanded Wharton's Jelly MSC | Immunosuppressive properties: suppress proliferation of activated T cells, increase production of regulatory T cells, shift immune response toward tolerance | Ages 18-75 years | Active, not recruiting | Day-45 treatment-related SAE |
| NCT04061876 | High-risk grade 2-4 aGVHD (based on ST2, REG3α, or other experiment object) | Randomized, phase 2 Ruxolitinib + corticosteroids vs corticosteroids alone | JAK1/2 inhibitor | Any donor type Ages 14-65 years | Recruiting | Day-28 ORR |
| NCT04167514 | High-risk aGVHD requiring corticosteroids (first-line therapy) | Randomized, double-blind, placebo-controlled, multicenter phase 3 AAT + corticosteroids vs corticosteroids alone | Serine protease inhibitor | Any donor type, conditioning Ages ≥18 years | Recruiting | Day-28 CR, PR |
| NCT04291261 | High-risk aGVHD, AA score 2-3 | Single-arm phase 2 ECP with methoxsalen +2 mg/kg corticosteroids | Induces apoptosis of mononuclear cells | Any donor type, conditioning Ages ≥18 years | Active, not recruiting | Day-28 CR |
| NCT04397367 | Grade 2-4 or high-risk aGVHD (based on ST2, REG3α, or other experiment object) | Nonrandomized Ruxolitinib + corticosteroids | JAK1/2 inhibitor | Any donor type Ages 14-65 years | Recruiting | Day-28 CR |
AAT, alpha-1 antitrypsin; ECP, extracorporeal photopheresis; IST, immunosuppressive therapy; JAK1, Janus kinase 1; MR, mixed response; MSC, mesenchymal stem cell; MTD, maximum tolerated dose; mTOR, mechanistic target of rapamycin; PR, partial response; PSGL-1, P-selectin glycoprotein 1; QOL, quality of life; REG3α, regenerating islet-derived 3-alpha; SAE, serious adverse event; ST2, suppressor of tumorigenesis; TMA, thrombotic microangiopathy; TRM, transplant-related mortality.