Clinical trials of microbiota therapies in cancer patients
| NCT identifier . | Study type . | Sample size . | Study population . | Study name . | Patient cohorts . | Delivery route . | Primary outcome . | Secondary outcomes . | Current status . |
|---|---|---|---|---|---|---|---|---|---|
| FMT in checkpoint inhibitor therapy | |||||||||
| NCT04038619 | Phase 1 single-arm | 40 | GU malignancy +ICI colitis, age >18 y | FMT for ICI Induced Diarrhea/Colitis in Genitourinary Cancer Patients | Loperamide +FMT | Colonoscopy | 1. FMT safety and tolerability 2. Colitis response | ICI colitis recurrence | Not yet recruiting |
| NCT03772899 | Phase 1 single-arm | 20 | Melanoma + anti-PD-1 immunotherapy, age >18 y | FMT in Combination with Immunotherapy in Melanoma Patients (MIMic) | ICI + FMT | Capsules | Safety, AE | 1. Immunotherapy response rate, 2. gut microbiome changes, 3. immune blood markers, 4. urine metabolomics | Recruiting |
| NCT03353402 | Phase 1 single-arm | 40 | Melanoma stage IV or unresectable stage III, age >18 y | FMT in Metastatic Melanoma Patients Who Failed Immunotherapy | FMT using ICI responder stool | Colonoscopy and capsules | 1. FMT-related AE, 2. FMT engraftment | Changes in: 1. immune cell composition, 2. immune cell activity | Recruiting |
| NCT03341143 | Phase 2 single-arm | 20 | Advanced melanoma + anti-PD-1 nonresponders, age >18 y | Phase 2 Feasibility Study of FMT in Advanced Melanoma Patients Not Responding to PD-1 Blockade | ICI + FMT using ICI responder stool | Colonoscopy | ORR | Changes in: 1. T-cell composition, 2. immune system subsets, 3. T-cell function | Recruiting |
| FMT for the prevention of complications in hematologic malignancies | |||||||||
| NCT02928523 | Phase 1/2 single-arm | 20 | AML, age >18 y | ODYSSEE Study: Prevention of dysbiosis complications with autologous FMT in AML undergoing intensive treatment: A feasibility and safety study | Autologous FMT | Not specified | Auto-FMT efficacy as measured by: 1. microbiota diversity and 2. MDRB eradication | Defining a dysbiosis biosignature | Completed |
| NCT03516461 | Nonrandomized, parallel-assignment, open label | 30 | Radiation enteritis, age >18 y | Efficacy and Safety of SMT and FMT in Radiation Enteritis | SMT or FMT | NGT/NDT or gastroscopy once per day (up to 3 times) | Change of toxicity grade | 1. Scores of GI symptoms, 2. KPS | Recruiting |
| FMT for the prevention of infections in HSCT | |||||||||
| NCT03678493 | Phase 2 RCT | 120 | AML +/− allo-HSCT, age >18 y | A Randomized Placebo-Controlled Clinical Trial of FMT in Patients with AML and Allogeneic HSCT Recipients | Randomized in 2:1 ratio to receive FMT vs placebo: cohort A (AML, induction) and cohort B (Allo-HSCT) | Capsules | Efficacy of FMT measured as incidence of infections | 1. Rate of FMT engraftment, 2. acute grade II-IV GVHD, 3. BSI of suspected gut origin, 4-6. bacterial, viral, and fungal infections | Recruiting |
| NCT02269150 | Phase 2 RCT | 59 | Allo-HSCT, low bacteroidetes abundance, age >18 y | Auto-FMT for Prophylaxis of Clostridium difficile Infection in Recipients of Allo-HSCT | Autologous FMT vs routine management | Retention enema | CDI | NA | Active, not recruiting |
| FMT for the prevention of GVHD in HSCT | |||||||||
| NCT03862079 | Phase 2 RCT | 120 | Allo-HSCT, age 16-75 y | Randomized Phase 2 Trial of TGD followed by FMT, FMT-Alone, or Standard of Care for Reduction in Acute Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients Given Broad-Spectrum Antibiotics | Arm A (TGD + FMT): TGD Oral piperacillin-tazobactam and nystatin until FMT; Arm B (FMT): FMT via enema within 3 wk after HSCT; Arm C (SOC): standard of care | Enema | 1. Acute GI GVHD; 2. RFS | 1.Microbiome diversity, 2. maximum stage lower GI GVHD, 3. acute GVHD, 4. AE and SAE, 5. BSI, 6. hematologic recovery, 7. characterization of the intestinal microbiota, 8. NRM, 9. OS | Not yet recruiting |
| NCT03720392 | Phase 2 double-blind RCT | 48 | Allo-HSCT, age 18-80 y | A Phase 2 Study of FMT in Recipients After Allogeneic Hematopoietic Cell Transplantation | Cohort A: FMT; cohort B: placebo capsule | Capsules | Proportion who achieve gut microbiome diversity at 1 mo | 1. Acute GVHD, 2. NRM , 3. Infection , 4. PFS, 5. OS , 6. GVHD / RFS | Recruiting |
| Other microbiota-related therapies in HSCT | |||||||||
| NCT02763033 | Phase 2 RCT | 70 | Allo-HSCT, age >9 y | Modification of the Intestinal Microbiome by Diet Intervention to Mitigate Acute Graft-Versus-Host Disease | Cohort A: potato starch; cohort B: placebo starch | Oral | Grade II-IV GVHD | NA | Recruiting |
| NCT02805075 | Phase 1 single-arm, dose escalation | 15 | Allo-HSCT, age >18 y | Single-arm Dose-Escalation Trial of Fructo-Oligosaccharides (FOS) in Patients Undergoing Allo-HSCT | FOS | Oral | Maximum tolerated dose | NA | Completed |
| NCT03039257 | Single-arm, dose escalation | 12 | Any HSCT, age >1 y | Single, High-Dose Vitamin A Replacement in Patients Undergoing HSCT and its Role on MBI-LCBI Rates | Single-dose vitamin A supplementation | Oral | Vitamin A level | MBI-LCBI | Completed |
| NCT02406651 | Phase 2a, single-arm | 27 | HSCT with grade II-IV lower GI-aGVHD, age 18-80 y | A Phase 2a Study of Recombinant Human Interleukin-22 IgG2-Fc (F652) in Combination with Systemic Corticosteroids for the Treatment of Newly Diagnosed Grade II-IV Lower GI a GVHD in HSCT | IL-22 IgG2-Fc, once per week for 4 wk + systemic corticosteroids | Intravenous (IV) | AE | 1. aGVHD response, 2.discontinuation of immunosuppressive medications, 3. OS | Active, not recruiting |
| NCT identifier . | Study type . | Sample size . | Study population . | Study name . | Patient cohorts . | Delivery route . | Primary outcome . | Secondary outcomes . | Current status . |
|---|---|---|---|---|---|---|---|---|---|
| FMT in checkpoint inhibitor therapy | |||||||||
| NCT04038619 | Phase 1 single-arm | 40 | GU malignancy +ICI colitis, age >18 y | FMT for ICI Induced Diarrhea/Colitis in Genitourinary Cancer Patients | Loperamide +FMT | Colonoscopy | 1. FMT safety and tolerability 2. Colitis response | ICI colitis recurrence | Not yet recruiting |
| NCT03772899 | Phase 1 single-arm | 20 | Melanoma + anti-PD-1 immunotherapy, age >18 y | FMT in Combination with Immunotherapy in Melanoma Patients (MIMic) | ICI + FMT | Capsules | Safety, AE | 1. Immunotherapy response rate, 2. gut microbiome changes, 3. immune blood markers, 4. urine metabolomics | Recruiting |
| NCT03353402 | Phase 1 single-arm | 40 | Melanoma stage IV or unresectable stage III, age >18 y | FMT in Metastatic Melanoma Patients Who Failed Immunotherapy | FMT using ICI responder stool | Colonoscopy and capsules | 1. FMT-related AE, 2. FMT engraftment | Changes in: 1. immune cell composition, 2. immune cell activity | Recruiting |
| NCT03341143 | Phase 2 single-arm | 20 | Advanced melanoma + anti-PD-1 nonresponders, age >18 y | Phase 2 Feasibility Study of FMT in Advanced Melanoma Patients Not Responding to PD-1 Blockade | ICI + FMT using ICI responder stool | Colonoscopy | ORR | Changes in: 1. T-cell composition, 2. immune system subsets, 3. T-cell function | Recruiting |
| FMT for the prevention of complications in hematologic malignancies | |||||||||
| NCT02928523 | Phase 1/2 single-arm | 20 | AML, age >18 y | ODYSSEE Study: Prevention of dysbiosis complications with autologous FMT in AML undergoing intensive treatment: A feasibility and safety study | Autologous FMT | Not specified | Auto-FMT efficacy as measured by: 1. microbiota diversity and 2. MDRB eradication | Defining a dysbiosis biosignature | Completed |
| NCT03516461 | Nonrandomized, parallel-assignment, open label | 30 | Radiation enteritis, age >18 y | Efficacy and Safety of SMT and FMT in Radiation Enteritis | SMT or FMT | NGT/NDT or gastroscopy once per day (up to 3 times) | Change of toxicity grade | 1. Scores of GI symptoms, 2. KPS | Recruiting |
| FMT for the prevention of infections in HSCT | |||||||||
| NCT03678493 | Phase 2 RCT | 120 | AML +/− allo-HSCT, age >18 y | A Randomized Placebo-Controlled Clinical Trial of FMT in Patients with AML and Allogeneic HSCT Recipients | Randomized in 2:1 ratio to receive FMT vs placebo: cohort A (AML, induction) and cohort B (Allo-HSCT) | Capsules | Efficacy of FMT measured as incidence of infections | 1. Rate of FMT engraftment, 2. acute grade II-IV GVHD, 3. BSI of suspected gut origin, 4-6. bacterial, viral, and fungal infections | Recruiting |
| NCT02269150 | Phase 2 RCT | 59 | Allo-HSCT, low bacteroidetes abundance, age >18 y | Auto-FMT for Prophylaxis of Clostridium difficile Infection in Recipients of Allo-HSCT | Autologous FMT vs routine management | Retention enema | CDI | NA | Active, not recruiting |
| FMT for the prevention of GVHD in HSCT | |||||||||
| NCT03862079 | Phase 2 RCT | 120 | Allo-HSCT, age 16-75 y | Randomized Phase 2 Trial of TGD followed by FMT, FMT-Alone, or Standard of Care for Reduction in Acute Graft-Versus-Host Disease of the Gastrointestinal Tract in Patients Given Broad-Spectrum Antibiotics | Arm A (TGD + FMT): TGD Oral piperacillin-tazobactam and nystatin until FMT; Arm B (FMT): FMT via enema within 3 wk after HSCT; Arm C (SOC): standard of care | Enema | 1. Acute GI GVHD; 2. RFS | 1.Microbiome diversity, 2. maximum stage lower GI GVHD, 3. acute GVHD, 4. AE and SAE, 5. BSI, 6. hematologic recovery, 7. characterization of the intestinal microbiota, 8. NRM, 9. OS | Not yet recruiting |
| NCT03720392 | Phase 2 double-blind RCT | 48 | Allo-HSCT, age 18-80 y | A Phase 2 Study of FMT in Recipients After Allogeneic Hematopoietic Cell Transplantation | Cohort A: FMT; cohort B: placebo capsule | Capsules | Proportion who achieve gut microbiome diversity at 1 mo | 1. Acute GVHD, 2. NRM , 3. Infection , 4. PFS, 5. OS , 6. GVHD / RFS | Recruiting |
| Other microbiota-related therapies in HSCT | |||||||||
| NCT02763033 | Phase 2 RCT | 70 | Allo-HSCT, age >9 y | Modification of the Intestinal Microbiome by Diet Intervention to Mitigate Acute Graft-Versus-Host Disease | Cohort A: potato starch; cohort B: placebo starch | Oral | Grade II-IV GVHD | NA | Recruiting |
| NCT02805075 | Phase 1 single-arm, dose escalation | 15 | Allo-HSCT, age >18 y | Single-arm Dose-Escalation Trial of Fructo-Oligosaccharides (FOS) in Patients Undergoing Allo-HSCT | FOS | Oral | Maximum tolerated dose | NA | Completed |
| NCT03039257 | Single-arm, dose escalation | 12 | Any HSCT, age >1 y | Single, High-Dose Vitamin A Replacement in Patients Undergoing HSCT and its Role on MBI-LCBI Rates | Single-dose vitamin A supplementation | Oral | Vitamin A level | MBI-LCBI | Completed |
| NCT02406651 | Phase 2a, single-arm | 27 | HSCT with grade II-IV lower GI-aGVHD, age 18-80 y | A Phase 2a Study of Recombinant Human Interleukin-22 IgG2-Fc (F652) in Combination with Systemic Corticosteroids for the Treatment of Newly Diagnosed Grade II-IV Lower GI a GVHD in HSCT | IL-22 IgG2-Fc, once per week for 4 wk + systemic corticosteroids | Intravenous (IV) | AE | 1. aGVHD response, 2.discontinuation of immunosuppressive medications, 3. OS | Active, not recruiting |
AE, adverse events; AML, acute myeloid leukemia; BSI, bloodstream infection; CDI, Clostridium difficile infection; FMT, fecal microbiota transplantation; FOS, fructo-oligosaccharides; GI, gastrointestinal; GVHD, graft-versus-host disease; GU, genitourinary; HSCT, hematopoietic stem cell transplantation; ICI, immune-checkpoint inhibitor; KPS, Karnofsky Performance Status; MBI-LCBI, mucosal barrier injury laboratory-confirmed bloodstream infection; MDRB, multidrug-resistant bacteria; NDT/NGT, nasoduodenal tube/nasogastric tube; NRM, nonrelapse mortality; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RFS, relapse-free survival; SAE, serious adverse events; SMT, selective microbiota transplantation; TGD, total gut decontamination.