Study to Evaluate CCS1477 (Inobrodib) in Haematological Malignancies
- Conditions
- Non Hodgkin LymphomaHaematological MalignancyAcute Myeloid LeukemiaHigher-risk Myelodysplastic SyndromeMultiple MyelomaPeripheral T Cell Lymphoma
- Interventions
- Registration Number
- NCT04068597
- Lead Sponsor
- CellCentric Ltd.
- Brief Summary
A Phase 1/2a study to assess the safety, tolerability, PK and biological activity of CCS1477 (inobrodib) in patients with Non-Hodgkin Lymphoma, Multiple Myeloma, Acute Myeloid Leukaemia or High Risk Myelodysplastic syndrome.
- Detailed Description
This includes patients with Peripheral T-cell lymphoma.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 250
- Provision of consent
- ECOG performance status 0-2
- Patients with confirmed (per standard disease specific diagnostic criteria), relapsed or refractory haematological malignancies (NHL, MM and AML)
- Must have previously received standard therapy
- Adequate organ function
- Intervention with any chemotherapy, investigational agents or other anti-cancer drugs within 14 days or 5 half-lives of the first dose
- Major surgical procedure or significant traumatic injury within 4 weeks of the first dose of study treatment
- Strong inhibitors of CYP3A4 or CYP3A4 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
- Strong inducers of CYP3A4 within 4 weeks of the first dose of study treatment
- Patients should discontinue statins prior to starting study treatment
- CYP2C8 substrates with a narrow therapeutic range taken within 2 weeks of the first dose of study treatment
- Any unresolved reversible toxicities from prior therapy >CTCAE grade 1 at the time of starting study treatment (except alopecia and grade 2 neuropathy)
- Any evidence of severe or uncontrolled systemic diseases
- Any known uncontrolled inter-current illness
- QTcF prolongation (> 480 msec)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description CCS1477 dose escalation NHL/MM CCS1477 CCS1477 monotherapy CCS1477 monotherapy expansion and combination dose finding and expansion - MM CCS1477 CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone CCS1477 monotherapy expansion and combination dose finding and expansion - AML CCS1477 CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax CCS1477 expansion phase NHL/Peripheral T-cell lymphoma CCS1477 CCS1477 monotherapy CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS CCS1477 CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax CCS1477 dose escalation AML/Higher risk MDS CCS1477 CCS1477 monotherapy CCS1477 monotherapy expansion and combination dose finding and expansion - MM Pomalidomide CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone CCS1477 monotherapy expansion and combination dose finding and expansion - MM Dexamethasone CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone CCS1477 monotherapy expansion and combination dose finding and expansion - AML Venetoclax CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax CCS1477 monotherapy expansion and combination dose finding and expansion - AML Azacitidine CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS Azacitidine CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS Venetoclax CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax
- Primary Outcome Measures
Name Time Method Incidence of treatment-related adverse events Up to 12 months Treatment-related adverse events and serious adverse events
Incidence of laboratory abnormalities Up to 12 months Laboratory abnormalities characterised by type, frequency, severity and timing
- Secondary Outcome Measures
Name Time Method Duration of Response Up to 12 months Defined as the time from start of treatment until disease progression
Response rate Up to 12 months Defined as number of patients who have a response according to
* RECIL criteria (NHL)
* IMWG criteria (Multiple myeloma)
* ELN recommendations 2017 (AML)AUC of CCS1477 35 days Area under the plasma concentration-time curve (AUC) from time 0 to the time of the last measurable concentration of CCS1477
Cmax of CCS1477 35 days Maximum observed plasma concentration (Cmax) of CCS1477
Trial Locations
- Locations (23)
Emory Winship Cancer Institute
🇺🇸Atlanta, Georgia, United States
Community Health Network
🇺🇸Indianapolis, Indiana, United States
The Center for Cancer and Blood Disorders (CCBD)
🇺🇸Bethesda, Maryland, United States
Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
University of Nebraska Medical Center
🇺🇸Omaha, Nebraska, United States
Penn Medicine - Abramson Cancer Center Perelman
🇺🇸Philadelphia, Pennsylvania, United States
University Hospital Vall D'Hebron
🇪🇸Barcelona, Spain
CIOCC Hospital Universitario HM Sanchinarro
🇪🇸Madrid, Spain
The Royal Marsden
🇬🇧Sutton, Surrey, United Kingdom
The Clatterbridge Cancer Centre NHS Foundation Trust,
🇬🇧Bebington, United Kingdom
University Hospitals Bristol
🇬🇧Bristol, United Kingdom
University Hospital of Wales
🇬🇧Cardiff, United Kingdom
Royal Derby Hospital
🇬🇧Derby, United Kingdom
Western General Hospital
🇬🇧Edinburgh, United Kingdom
Gartnavel General Hospital
🇬🇧Glasgow, United Kingdom
Leicester Royal Infirmary
🇬🇧Leicester, United Kingdom
Sarah Cannon Research Institute UK
🇬🇧London, United Kingdom
NIHR University College London Clinical Research Facility
🇬🇧London, United Kingdom
Imperial College
🇬🇧London, United Kingdom
The Christie Hospital
🇬🇧Manchester, United Kingdom
Newcastle upon Tyne Hospitals
🇬🇧Newcastle upon Tyne, United Kingdom
Cancer and Haematology Centre
🇬🇧Oxford, United Kingdom
University Hospital of Southampton
🇬🇧Southampton, United Kingdom