Clinical trial NCT04068597: Study to Evaluate CCS1477 (Inobrodib) in Haematological Malignancies
Official title: An Open-label Phase I/IIa Study to Evaluate the Safety and Efficacy of CCS1477 as Monotherapy and in Combination in Patients With Advanced Haematological Malignancies.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Haematological Malignancy
Acute Myeloid Leukemia
Non Hodgkin Lymphoma
Multiple Myeloma
Higher-risk Myelodysplastic Syndrome
Peripheral T Cell Lymphoma
Lead sponsor: CellCentric Ltd.
Sponsor class: INDUSTRY
First posted: 2019-08-28
Enrollment: 250
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: The RP2D/MTD dose will be determined in Parts A and B. Parts C, D, E and F of the study may recruit patients concurrently.
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Incidence of treatment-related adverse events
timeFrame: Up to 12 months
measure: Incidence of laboratory abnormalities
timeFrame: Up to 12 months
Secondary outcomes:
measure: Response rate
timeFrame: Up to 12 months
measure: Duration of Response
timeFrame: Up to 12 months
measure: AUC of CCS1477
timeFrame: 35 days
measure: Cmax of CCS1477
timeFrame: 35 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Winship Cancer Institute
state: Georgia
city: Indianapolis
country: United States
facility: Community Health Network
state: Indiana
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders (CCBD)
state: Maryland
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Omaha
country: United States
facility: University of Nebraska Medical Center
state: Nebraska
city: Philadelphia
country: United States
facility: Penn Medicine - Abramson Cancer Center Perelman
state: Pennsylvania
city: Barcelona
country: Spain
facility: University Hospital Vall D'Hebron
city: Madrid
country: Spain
facility: CIOCC Hospital Universitario HM Sanchinarro
city: Sutton
country: United Kingdom
facility: The Royal Marsden
state: Surrey
city: Bebington
country: United Kingdom
facility: The Clatterbridge Cancer Centre NHS Foundation Trust,
city: Bristol
country: United Kingdom
facility: University Hospitals Bristol
city: Cardiff
country: United Kingdom
facility: University Hospital of Wales
city: Derby
country: United Kingdom
facility: Royal Derby Hospital
city: Edinburgh
country: United Kingdom
facility: Western General Hospital
city: Glasgow
country: United Kingdom
facility: Gartnavel General Hospital
city: Leicester
country: United Kingdom
facility: Leicester Royal Infirmary
city: London
country: United Kingdom
facility: Sarah Cannon Research Institute UK
city: London
country: United Kingdom
facility: NIHR University College London Clinical Research Facility
city: London
country: United Kingdom
facility: Imperial College
city: Manchester
country: United Kingdom
facility: The Christie Hospital
city: Newcastle upon Tyne
country: United Kingdom
facility: Newcastle upon Tyne Hospitals
city: Oxford
country: United Kingdom
facility: Cancer and Haematology Centre
city: Southampton
country: United Kingdom
facility: University Hospital of Southampton
Study officials:
affiliation: The Christie NHS Foundation Trust
name: Tim Somervaille
role: PRINCIPAL_INVESTIGATOR
References: