Table 2.
Recruiting info and preliminary results of clinical trials with ibruitinib and acalabrutinib in human diseases beyond B cell malignancies.
| Clinical trial | Recruitment # | Method of | Sponsor | Location of trial | Trial results | Major toxicities | Ref. |
|---|---|---|---|---|---|---|---|
| Actual/Target | recruiment | ||||||
| Hematological cancers | |||||||
| NCT03267186 | 8/50 | Site-specific | Andrew Rezvani, Stanford University | United States | Not posted | Not posted | |
| NCT03642236 | 122/122 | Enrolling by invitation | Nanfang Hospital of Southern Medical University | China | Not posted | Not posted | |
| NCT03359460 | 20/20 | Site-specific | Brian Jonas | United States | Not posted | Not posted | |
| NCT02553941 | 21/24 | Not specified | Brian Jonas | United States | Not posted | Not posted | |
| NCT02415608 | 4/11 (Terminated due to slow accrual) | Site-specific | Jason Robert Gotlib | United States | ORR to ibrutinib is 0% in 4 patients with advanced systemic mastocytosis. | Fatigue, anemia, gastrointestinal disorders | |
| NCT02309580 | Recruiting/19 | Site-specific | Memorial Sloan Kettering Cancer Center | United States | ORR to ibrutinib is 8% in 13 patients with R/R TCL. | Thrombocytopenia, diarrhea, fatigue | (49) |
| NCT03873493 | 14/37 | Not specified | AbbVie | United States | Ibrutinib plus venetoclax produces clinical responses in two patients with R/R T-PLL, but the results of other patients are not posted. | Not posted | (50) |
| Solid tumors | |||||||
| NCT02403271 | 124/160 | Not specified | Pharmacyclics LLC | United States | ORR to ibrutinib in combination with durvalumab is 1.9% in 105 patients with R/R NSCLC, breast or pancreatic cancer. | Fatigue, gastrointestinal disorders, anemia | |
| NCT03379428 | Recruiting/51 | Site-specific | US Oncology Research | United States | Not posted | Not posted | |
| NCT03332498 | 40/42 | Site-specific | H. Lee Moffitt Cancer Center and Research Institute | United States | Disease control rate by ibrutinib plus pembrolizumab is 41.9% in 31 patients with metastatic colorectal cancers, but this trial lacks a control arm with pembrolizumab alone or plus placebo. | Anemia, fatigue, elevated alkaline phosphatase | (51) |
| NCT02599324 | 261/189 | Not specified | Pharmacyclics LLC | United States | Not posted | Not posted | |
| NCT03535350 | Recruiting/36 | Site-specific | Case Comprehensive Cancer Center | United States | Not posted | Not posted | |
| NCT02586857 | 24/72 | Not specified | Acerta Pharma BV | United States | ORR to 200 mg acalabrutinib is 6.7% in 15 patients and ORR to 400 mg acalabrutinib is 11% in 9 patients with recurrent glioblastoma. | Gastrointestinal disorders, fatique, fall injury | |
| NCT02454179 | 78/74 | Site-specific | Acerta Pharma BV | United States | ORR is not improved by 100 mg (BID) acalabrutinib plus pembrolizumab (16.7%; 5/30) as compared to pembrolizumab monotherapy (18.9%; 7/37) in patients with advanced HNSCC. | Fatigue, anemia, gastrointestinal disorders, decreased appetite | |
| NCT03646461 | Recruiting/39 | Site-specific | University of California, San Diego | United States | Not posted | Not posted | |
| NCT02899078 | 31/30 | Site-specific | University of California, Davis | United States | Not posted | Not posted | |
| NCT02448303 | 74/74 | Site-specific | Acerta Pharma BV | United States | ORR is not improved by 100 mg (BID) acalabrutinib plus pembrolizumab (14.3%; 4/28) as compared to pembrolizumab monotherapy (12.9%; 4/31) in patients with advanced NSCLC. | Gastrointestinal disorders, decreased appetite, dyspnoea | |
| NCT02321540 | 13/38 | Site-specific | M.D. Anderson Cancer Center | United States | Not posted | Not posted | |
| NCT03021460 | 23/51; recruiting | Site-specific | Mayo Clinic | United States | Not posted | Not posted | |
| NCT02581930 | 18/32 | Site-specific | National Cancer Institute (NCI) | United States | ORR to ibrutinib is 0% in 18 patients with refractory metastatic cutaneous melanoma. | Fatigue, anorexia, hyponatremia, gastrointestinal disorders | (52) |
| NCT02884453 | Recruiting/17 | Not specified | Royal Marsden NHS Foundation Trust | United Kingdom | Not posted | Not posted | |
| NCT02537444 | 78/76 | Site-specific | Acerta Pharma BV | United States | ORR to 100 mg (BID) acalabrutinib monotherapy is 2.9% (1/35) and ORR to acalabrutinib plus pembrolizumab is 9.1% (3/33) in patients with refractory ovarian cancer. | Gastrointestinal disorders, headache, fatique, anemia | |
| NCT02362048 | 77/76 | Site-specific | Acerta Pharma BV | United States | ORR to 100 mg (BID) acalabrutinib monotherapy is 0% (0/37) and ORR to acalabrutinib plus pembrolizumab is 7.5% (3/40) in patients with refractory or metastatic pancreatic cancer. | Gastrointestinal disorders, headache, fatique, anemia, decreased appetite | (53) |
| NCT02436668 | 430/326 | Global | Pharmacyclics LLC. | United States, European Union, South Korea | As compared to placebo plus gemcitabine/Nab-paclitaxel, ibrutinib plus gemcitabine/Nab-paclitaxel did not improve the progression free survival (PFS) or overall survival (OS) in patients with metastatic pancreatic cancer. | Gastrointestinal disorders, thrombocytopenia | |
| NCT02562898 | 18/35 | Site-specific | Margaret Tempero | United States | CA19-9 clinical response rate to ibrutinib plus gemcitabine/Nab-paclitaxel is <1% in patients with metastatic pancreatic cancer. | Gastrointestinal disorders, fatique, myalgia, sepsis | (54) |
| NCT02575300 | 20/51 | Site-specific | H. Lee Moffitt Cancer Center | United States | ORR to ibrutinib is 0% in 20 patients with advanced carcinoid and pancreatic neuroendocrine tumors | Gastrointestinal disorders, fatique, arthralgia | |
| NCT02643667 | Recruiting/36 | Site-specific | Washington University School of Medicine | United States | Not posted | Not posted | |
| NCT02351739 | 78/74 | Not specified | Acerta Pharma BV | United States | ORR is not improved by 100 mg (BID) acalabrutinib plus pembrolizumab (23.5%; 8/34) as compared to pembrolizumab monotherapy (29%; 9/31) in patients with platinum resistant urothelial bladder cancer. | Fatique, gastrointestinal disorders, increased alanine aminotransferase | (55) |
| NCT03525925 | 15/15 | Site-specific | Ohio State University Cancer Center | United States | Not posted | Not posted | |
| Graft-versus-host disease | |||||||
| NCT04294641 | Recruiting/40 | Site-specific | National Cancer Institute (NCI) | United States | Not posted | Not posted | |
| NCT03689894 | Recruiting/15 | Site-specific | Dartmouth-Hitchcock Medical Center | United States | Not posted | Not posted | |
| NCT04235036 | Recruiting/35 | Site-specific | Northside Hospital, Inc. | United States | Not posted | Not posted | |
| NCT02959944 | 193/186 | Global | Pharmacyclics LLC. | 14 different countries | ORR is minimally improved by ibrutinib plus prednisone (41.1%; 39/95) as compared to placebo plus prednisone (36.7%; 36/98) in patients with new onset cGVHD. | Peripheral edema, insomnia, thrombocytopenia | |
| NCT03474679 | 19/17 | Not specified | Janssen Pharmaceutical K.K | Japan | Not posted | Not posted | |
| NCT02195869 | 45/39 | Not specified | Pharmacyclics LLC. | United States | ORR to ibrutinib is 69% in 42 patients with cGVHD who were steroid-dependent or -refractory. | Fatigue, gastrointestinal disorders, muscle spasms, bruising, pneumonia | (56, 57) |
| NCT04198922 | Recruiting/50 | Not specified | Fred Hutchinson Cancer Research Center | United States | Not posted | Not posted | |
| NCT03790332 | 58/44 | Global | Pharmacyclics LLC. | 14 different countries | Not posted | Not posted | (58) |
| Autoimmune diseases | |||||||
| NCT04398459 | Recruiting/18 | Site-specific | Institute of Hematology & Blood Diseases Hospital | China | Not posted | Not posted | |
| NCT03827603 | 50/50 | Site-specific | Eugene Nikitin | Russian Federation | Not posted | Not posted | |
| NCT04657094 | Recruiting/22 | Site-specific | City of Hope Medical Center | United States | Not posted | Not posted | |
| NCT02387762 | 31/70 | Not specifed | Acerta Pharma BV | United States | Disease activity score 28-CRP (DAS28-CRP) at Week 4 is not improved by 15 mg (QD) acalabrutinib plus methotrexate (5.40; n=15) as compared to placebo plus methotrexate (5.05; n=15) in patients with RA. | Anemia | |
| Allergic diseases | |||||||
| NCT03149315 | 6/6 | Site-specific | Ann & Robert H Lurie Children's Hospital of Chicago | United States | Short-term ibrutinib therapy suppreses skin test responses and eliminates IgE-mediated basophil activation in 6 patients with an allergy to peanut or tree nuts (ORR: 100%). | No common side effects observed | (59) |
| COVID-19 | |||||||
| NCT04375397 | 46/46 | Not specified | Abbvie | United States | Not posted | Not posted | |
| NCT04439006 | Recruiting/78 | Site-specific | Jennifer Woyach, Ohio State University Cancer Center | United States | Not posted | Not posted | |
| NCT04647669 | Not yet recruiting/100 | Site-specific | The University of The West Indies | Jamaica | Not posted | Not posted | |
| NCT04346199 | 177/428 | Global | AstraZeneca | Worldwide | Percentage of participants that remained alive and free of respiratory failure is not improved by acalabrutinib plus best supportive care (BSC) (n=89) as compared to BSC alone (n=88) in patients hospitalized with COVID-19. | Headache | |
| NCT04380688 | 62/60 | Not specified | AstraZeneca | United States | Percentage of participants that remained alive and free of respiratory failure is not improved by acalabrutinib plus BSC (n=31) as compared to BSC alone (n=31) in patients hospitalized with COVID-19. | Headache | |
| NCT04564040 | 20/40 | Site-specific | AstraZeneca | Germany | Not posted | Not posted | |
| NCT04665115 | Not yet recruiting/134 | Site-specific | Academic and Community Cancer Research United | United States | Not posted | Not posted |