Study to Evaluate CCS1477 in Haematological Malignancies

Sponsor

CellCentric Ltd. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04068597

Collaborator

(none)

250

Enrollment

Locations

Arms

55.7

Anticipated Duration (Months)

16.7

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

A Phase 1/2a study to assess the safety, tolerability, PK and biological activity of CCS1477 in patients with Non-Hodgkin Lymphoma, Multiple Myeloma, Acute Myeloid Leukaemia or High Risk Myelodysplastic syndrome.

Condition or Disease	Intervention/Treatment	Phase
Haematological Malignancy Acute Myeloid Leukemia Non Hodgkin Lymphoma Multiple Myeloma Higher-risk Myelodysplastic Syndrome	Drug: CCS1477 Drug: Pomalidomide Drug: Dexamethasone Drug: Azacitidine Drug: Venetoclax	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

250 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

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.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.

Masking:

None (Open Label)

Primary Purpose:

Treatment

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.

Actual Study Start Date :

Aug 9, 2019

Anticipated Primary Completion Date :

Mar 31, 2024

Anticipated Study Completion Date :

Mar 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: CCS1477 dose escalation NHL/MM CCS1477 monotherapy	Drug: CCS1477 Oral capsule
Experimental: CCS1477 dose escalation AML/Higher risk MDS CCS1477 monotherapy	Drug: CCS1477 Oral capsule
Experimental: CCS1477 expansion phase NHL CCS1477 monotherapy	Drug: CCS1477 Oral capsule
Experimental: CCS1477 monotherapy expansion and combination dose finding and expansion - MM CCS1477 monotherapy, CCS1477 combination with pomalidomide-dexamethasone	Drug: CCS1477 Oral capsule Drug: Pomalidomide oral capsule Drug: Dexamethasone oral tablet
Experimental: CCS1477 monotherapy expansion and combination dose finding and expansion - AML CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax	Drug: CCS1477 Oral capsule Drug: Azacitidine Powder suspension for Injection Drug: Venetoclax Oral tablet
Experimental: CCS1477 monotherapy expansion and combination dose finding and expansion - Higher risk MDS CCS1477 monotherapy, CCS1477 combination with azacitidine, CCS1477 combination with azacitidine and venetoclax	Drug: CCS1477 Oral capsule Drug: Azacitidine Powder suspension for Injection Drug: Venetoclax Oral tablet

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Phoenix	Arizona	United States	85054
2	Institute Bergonie	Bordeaux		France	33000
3	Institute Gustave Roussy	Villejuif		France	94805
4	University Hospital Vall D'Hebron	Barcelona		Spain	08035
5	CIOCC Hospital Universitario HM Sanchinarro	Madrid		Spain	28050
6	Karolinska Institute	Stockholm		Sweden	171 76
7	The Royal Marsden	Sutton	Surrey	United Kingdom	SM2 5PT
8	University Hospital of Wales	Cardiff		United Kingdom
9	Western General Hospital	Edinburgh		United Kingdom	EH4 2XU
10	Gartnavel General Hospital	Glasgow		United Kingdom	G12 0YN
11	Leicester Royal Infirmary	Leicester		United Kingdom
12	NIHR University College London Clinical Research Facility	London		United Kingdom	W1T 7HA
13	The Christie Hospital	Manchester		United Kingdom
14	Cancer and Haematology Centre	Oxford		United Kingdom
15	University Hospital of Southampton	Southampton		United Kingdom	SO16 6YD