Acute Myeloid Leukemia, Haematological Malignancy, Higher-risk Myelodysplastic Syndrome, Multiple Myeloma, Non Hodgkin Lymphoma, Peripheral T Cell Lymphoma
Conditions
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.
Interventions
DRUGCCS1477
Oral capsule
DRUGPomalidomide
oral capsule
DRUGDexamethasone
oral tablet
DRUGAzacitidine
Powder suspension for Injection
DRUGVenetoclax
Oral tablet
DRUGBortezomib
Powder for solution for injection
DRUGIxazomib
Oral capsule
DRUGElranatamab
Solution for injection
DRUGTeclistamab
Solution for injection
DRUGLenalidomide
Oral capsule
DRUGDaratumumab
Solution for injection, concentrate for solution for infusion
Sponsors
CellCentric Ltd.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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 (\> 470 msec)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Duration of Response | Up to 12 months | Defined as the time from start of treatment until disease progression |
| 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 |
Countries
France, Spain, Sweden, United Kingdom, United States
Contacts
CONTACTTomasz Knurowski, PhD
CONTACTKaren Clegg, MD, MFPM
PRINCIPAL_INVESTIGATORTim Somervaille
The Christie NHS Foundation Trust
Outcome results
None listed