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A Study of Pevonedistat in People With Blood Cancers or Solid Tumors With Kidney or Liver Problems
Phase 1 trial testing Azacitidine in Myelodysplastic Syndromes in 17 participants. Completed in 19 April 2022.
| Lead sponsor | Takeda |
|---|---|
| Phase | Phase 1 |
| Status | Completed |
| Study type | INTERVENTIONAL |
| Allocation | non randomized |
| Design | sequential |
| Masking | none |
| Primary purpose | other |
| Enrollment | 17 |
| Start date | 10 July 2019 |
| Primary completion | 19 March 2021 |
| Estimated completion | 19 April 2022 |
| Sites | 8 locations across United States, Spain |
Takeda — full company profile →
18 and older, any sex, with Myelodysplastic Syndromes or Leukemia, Myelomonocytic, Chronic. Patients with the condition only — healthy volunteers not accepted.
Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.
| Group | Value | 95% CI |
|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 1168.616 | ± 69.4811 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 1293.467 | ± 22.0685 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 1050.553 | ± 69.4854 |
| Group | Value | 95% CI |
|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 1120.759 | ± 73.3956 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 1267.523 | ± 22.1528 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 1020.344 | ± 71.9314 |
| Group | Value | 95% CI |
|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 262.9 | ± 188.54 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 180.2 | ± 37.66 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 148.9 | ± 30.09 |
| Group | Value | 95% CI |
|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 6.957 | 4.25 – 13.88 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 8.493 | 7.31 – 10.29 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 9.612 | 7.49 – 11.03 |
| Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 8.795 | 7.03 – 9.22 |
| Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 10.248 | 9.78 – 10.72 |
| Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 8.98 | 8.98 – 8.98 |
| Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 6.477 | 3.93 – 13.37 |
| Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 6.79 | 6.79 – 6.79 |
| Group | Value | 95% CI |
|---|---|---|
| Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 74.73 | ± 14.941 |
| Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 44.74 | ± 24.579 |
| Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 128.00 | ± NA |
| Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 141.55 | ± 37.468 |
| Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 75.80 | ± NA |
| Group | Value | 95% CI |
|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 5.800 | ± 18.2880 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 7.073 | ± 12.2269 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 5.529 | ± 2.0462 |
| Group | Value | 95% CI |
|---|---|---|
| Part B: Control Arm | 645.4 | ± 34.40 |
| Part B: Renal Arm | 918.6 | ± 98.14 |
| Part B: Mild Hepatic Arm | 834.8 | ± 38.23 |
| Group | Value | 95% CI |
|---|---|---|
| Part B: Control Arm | 0.325 | 0.08 – 0.75 |
| Part B: Renal Arm | 0.500 | 0.32 – 0.53 |
| Part B: Mild Hepatic Arm | 0.250 | 0.12 – 0.75 |
| Group | Value | 95% CI |
|---|---|---|
| Part B: Control Arm | 0.706 | 0.57 – 1.47 |
| Part B: Renal Arm | 1.020 | 0.79 – 1.76 |
| Part B: Mild Hepatic Arm | 0.694 | 0.67 – 1.13 |
| Group | Value | 95% CI |
|---|---|---|
| Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 574.168 | ± 19.6797 |
| Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 396.240 | ± 14.4663 |
| Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 884.974 | ± NA |
| Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 848.866 | ± 25.6831 |
| Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 431.699 | ± NA |
| Group | Value | 95% CI |
|---|---|---|
| Part B: Control Arm | 822.457 | ± 31.1338 |
| Part B: Renal Arm | 1331.654 | ± 63.1278 |
| Part B: Mild Hepatic Arm | 751.448 | ± 35.3760 |
| Group | Value | 95% CI |
|---|---|---|
| Part A: Control Arm: Pevonedistat 20 mg/m^2 | 32.149 | ± 64.5489 |
| Part A: Renal Arm: Pevonedistat 20 mg/m^2 | 29.167 | ± 31.5125 |
| Part A: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 | 34.476 | ± 56.9322 |
| Part B: Renal Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 32.721 | ± 36.0104 |
| Part B: Mild Hepatic Arm: Pevonedistat 10 mg/m^2 + Azacitidine 75 mg/m^2 | 51.628 | ± 9.1794 |
| Part B: Renal Arm: Pevonedistat 15 mg/m^2 + Azacitidine 75 mg/m^2 | 32.361 | ± NA |
| Part B: Control Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 44.259 | ± 24.9426 |
| Part B: Mild Hepatic Arm: Pevonedistat 20 mg/m^2 + Azacitidine 75 mg/m^2 | 65.746 | ± NA |
Time frame: From the study start up to end of study (up to approximately 2 years 9 months). Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.
| Reaction | System | Part A: Control Arm | Part A: Renal Arm | Part A: Mild Hepatic Arm | Part B: Control Arm | Part B: Renal Arm | Part B: Mild Hepatic Arm |
|---|---|---|---|---|---|---|---|
| Febrile neutropenia | Blood and lymphatic system disorders | — | — | — | — | — | — |
| Acute kidney injury | Renal and urinary disorders | — | — | — | — | — | — |
| Acute myeloid leukaemia | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — | — | — | — | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Bladder transitional cell carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | — | — | — | — | — | — |
| Chronic kidney disease | Renal and urinary disorders | — | — | — | — | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — | — | — | — | — |
| Escherichia bacteraemia | Infections and infestations | — | — | — | — | — | — |
| Fatigue | General disorders | — | — | — | — | — | — |
| Haemorrhage intracranial | Nervous system disorders | — | — | — | — | — | — |
| Klebsiella bacteraemia | Infections and infestations | — | — | — | — | — | — |
| Leukocytosis | Blood and lymphatic system disorders | — | — | — | — | — | — |
| Pneumonia pseudomonal | Infections and infestations | — | — | — | — | — | — |
| Pneumonia staphylococcal | Infections and infestations | — | — | — | — | — | — |
| Pyrexia | General disorders | — | — | — | — | — | — |
| Rectal haemorrhage | Gastrointestinal disorders | — | — | — | — | — | — |
| Sepsis | Infections and infestations | — | — | — | — | — | — |
| Sinusitis | Infections and infestations | — | — | — | — | — | — |
| Thyroid gland abscess | Infections and infestations | — | — | — | — | — | — |
| Tumour lysis syndrome | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Urinary tract infection | Infections and infestations | — | — | — | — | — | — |
| White blood cell count increased | Investigations | — | — | — | — | — | — |
| Reaction | System | Part A: Control Arm | Part A: Renal Arm | Part A: Mild Hepatic Arm | Part B: Control Arm | Part B: Renal Arm | Part B: Mild Hepatic Arm |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | — | — | — | — | — | — |
| Cough | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Fatigue | General disorders | — | — | — | — | — | — |
| White blood cell count increased | Investigations | — | — | — | — | — | — |
| Asthenia | General disorders | — | — | — | — | — | — |
| Blood creatinine increased | Investigations | — | — | — | — | — | — |
| Constipation | Gastrointestinal disorders | — | — | — | — | — | — |
| Diarrhoea | Gastrointestinal disorders | — | — | — | — | — | — |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Pain in extremity | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Anaemia | Blood and lymphatic system disorders | — | — | — | — | — | — |
| Arthralgia | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Back pain | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Blood bilirubin increased | Investigations | — | — | — | — | — | — |
| Bone pain | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Conjunctival haemorrhage | Eye disorders | — | — | — | — | — | — |
| Decreased appetite | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Epistaxis | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Erythema | Skin and subcutaneous tissue disorders | — | — | — | — | — | — |
| Hypoalbuminaemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hypokalaemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hyponatraemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Hypophosphataemia | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Injection site erythema | General disorders | — | — | — | — | — | — |
| Injection site pain | General disorders | — | — | — | — | — | — |
| Myalgia | Musculoskeletal and connective tissue disorders | — | — | — | — | — | — |
| Neutropenia | Blood and lymphatic system disorders | — | — | — | — | — | — |
| Neutrophil count decreased | Investigations | — | — | — | — | — | — |
| Platelet count decreased | Investigations | — | — | — | — | — | — |
| Pneumonia | Infections and infestations | — | — | — | — | — | — |
| Rhinorrhoea | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Acidosis | Metabolism and nutrition disorders | — | — | — | — | — | — |
| Alanine aminotransferase increased | Investigations | — | — | — | — | — | — |
| Allergic cough | Respiratory, thoracic and mediastinal disorders | — | — | — | — | — | — |
| Anal infection | Infections and infestations | — | — | — | — | — | — |
| Anxiety | Psychiatric disorders | — | — | — | — | — | — |
| Aphthous ulcer | Gastrointestinal disorders | — | — | — | — | — | — |
| Aspartate aminotransferase increased | Investigations | — | — | — | — | — | — |
| Bladder spasm | Renal and urinary disorders | — | — | — | — | — | — |
| Blast cell count increased | Investigations | — | — | — | — | — | — |
Most-reported serious reactions: Febrile neutropenia, Acute kidney injury, Acute myeloid leukaemia, Back pain, Bladder transitional cell carcinoma, Chronic kidney disease, Diarrhoea, Escherichia bacteraemia.
Data from ClinicalTrials.gov NCT03814005 adverse events section.
Pevonedistat is a medicine to treat people with blood cancers or solid tumors. The main aim of the study is to learn about the levels of pevonedistat in the blood of participants with blood cancers or solid tumors, who also have severe kidney problems or mild to moderate liver problems. The information from this study will be used to work out the best dose of pevonedistat to give people with these conditions in future studies. At the first visit, the study doctor will check who can take part in the study. This study is in 2 parts: A and B. Part A Participants will be placed into 1 of 4 treatment groups depending on how severe their kidney and liver problems are. All participants will receive 1 dose of pevonedistat as a slow injection in their vein (infusion). Then, the study doctors will check the levels of pevonedistat in the blood of the participants for 3 days after the infusion. They will also check if the participants have any side effects from pevonedistat. Participants will be asked to continue to Part B. Those who don't want to continue will visit the clinic 30 days later for a final check-up. Part B Participants who agree to participate into Part B will receive an infusion of pevonedistat on specific days during a 21-day or 28-day cycle. The cycle time will depend on what type of cancer the participants have. Participants will also be treated with standard of care medicines for their kidney and liver problems during this time. In the first cycle, the study doctors will also check the levels of pevonedistat in the blood and urine of participants for 3 days after the infusion. Participants will continue with cycles of treatment together with standard of care medicines until their condition gets worse or they have too many side effects from the treatment. When treatment has finished, participants will visit the clinic 10 days later for a final check-up.
8 peer-reviewed publications reference this trial (live from Europe PMC):
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