Acute Myeloid Leukaemia (AML)/high-risk Myelodysplastic Syndrome (MDS), Multiple Myeloma (MM) and Non-Hodgkin Lymphoma(NHL).
Conditions
Interventions
Product Code: CCS1477 10 mg
Pharmaceutical Form: Capsule, soft
INN or Proposed INN: CCS1477
Current Sponsor code: CCS1477-M
Other descriptive name: Inhibitor of the bromodomain of p300 & CBP
Concentra
Sponsors
CellCentric Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses. 2.Willing and able to participate in all required evaluations and procedures in this study protocol. 3.Men and women =18 years of age. 4.Eastern Cooperative Oncology Group (ECOG) performance status of =2. 5.Patients with confirmed (per standard disease specific diagnostic criteria), relapsed or refractory haematological malignancies (NHL, MM and AML). Patients will include but are not limited to the following: •B-cell non-Hodgkin lymphoma (including Richter’s Syndrome) •T-cell non-Hodgkin lymphoma •Multiple myeloma •AML/secondary AML (patients with acute promyelocytic leukemia (APL) (FAB subtype M3) will be excluded). •High-risk MDS; according to revised International Prognostic Scoring System (IPSS-R). 6.Must have received standard therapy (for the majority of therapeutic indications - at least 2 prior lines of therapy) - refer to relevant disease guidelines, such as European Society for Medical Oncology (ESMO), International Myeloma Working Group (IMWG) or National Comprehensive Cancer Network (NCCN) guidelines. In circumstances where there may be no standard of care, or intensive treatment would not be tolerable or is refused, patients may be considered eligible for the study upon consultation and agreement between the medical monitor and the treating Investigator. 7.Adequate haematologic function defined as: •Absolute neutrophil count (ANC) =1000 cells/mm3 (1.0 x 10^9/L). •Platelet count without requiring ongoing blood product support =75,000 cells/mm3 (75 x 10^9/L). Platelet transfusions are not permitted within 3 days of screening. •Haemoglobin level =80 g/L. This criterion does not apply to AML/MDS patients. Patients with other malignancies involving bone marrow with parameters below the threshold may be considered eligible following discussion with the medical monitor. •For AML, WBC must be 2.5 g/dL Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 15 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 75
Exclusion criteria
Exclusion criteria: Patients must not enter the study if any of the following exclusion criteria are fulfilled 1.Treatment with any of the following: •Any investigational agent, chemotherapy, immunotherapy or anticancer agents from a previous clinical study within 14 days or 5 half-lives of first dose of study treatment. Shorter wash-out may be considered for immunotherapies after discussion with medical monitor. •Strong inducers of CYP3A4 taken within 4 weeks of the first dose of study treatment or whilst on study treatment. •Strong inhibitors of CYP3A4, CYP3A4 substrates with a narrow therapeutic range, CYP2C8 substrates with a narrow therapeutic range or CYP3A4 sensitive substrates taken within 2 weeks of the first dose of study treatment or while on study treatment. Washout periods may be reduced for specific medications (eg. statins) following discussion with the medical monitor. •Radiotherapy with a wide field of radiation or to more than 30% of the bone marrow within 4 weeks of the first dose of study treatment; palliative radiotherapy to =30% of the bone marrow within 2 weeks of the first dose of study treatment. A shorter wash-out period may be considered for palliative radiotherapy after discussion with medical monitor. •Herbal medications taken within 7 days of the first dose of study treatment (4 weeks for St John’s wort) or while on study treatment. •Statins; patients should discontinue statins 5 half-lives prior to starting study treatment. •Steroids use >10mg daily prednisolone or equivalent within 2 weeks of the first dose of study treatment. •Major surgery within 4 weeks of the first dose of study treatment. 2.With the exception of alopecia, and CTCAE Grade 2 neuropathy, any unresolved toxicities from prior therapy > Grade 1 at the time of starting study treatment. 3.Presence of, or history of, CNS lymphoma, symptomatic leptomeningeal disease, or spinal cord compression. 4.History of prior non-haematologic malignancy except for the following: •Adequately treated carcinoma in situ or non-melanomatous skin cancer •Malignancy treated with curative intent or in remission for >6 months after the last therapy may be eligible after discussion with medical monitor. Maintenance treatment (eg. hormonal therapy) is allowed. 5.Any evidence of severe or uncontrolled systemic disease (e.g. current unstable or uncompensated respiratory or cardiac conditions; history of, or active, bleeding diatheses; uncontrolled active systemic infection, including hepatitis B, hepatitis C and human immunodeficiency virus (HIV)*), which in the investigator’s opinion makes it undesirable for the patient to participate in the study or which would jeopardise compliance with the protocol. *Active viral infection is defined as requiring antiviral therapy. Screening for chronic conditions is not required. 6.Repeatable QTcF prolongation (>480 msec). 7.History of severe allergic or anaphylactic reactions or history of hypersensitivity to active or inactive excipients of CCS1477. 8.Female patients who are pregnant or breast-feeding at study entry. 9.Judgment by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the safety and tolerability of CCS1477 in patients with blood/bone marrow cancers.;Secondary Objective: To investigate the efficacy of CCS1477 in patients with blood/bone marrow cancers. To understand how the body handles the study medication (pharmacokinetics) of CCS1477, following a single dose and after multiple dosing.;Primary end point(s): The primary outcome measure for the study is: Safety and tolerability of CCS1477 as monotherapy. Safety and tolerability will be assessed in terms of AEs, laboratory data, vital signs and ECG changes. These will be collected for all patients. Appropriate summaries of these data will be presented.;Timepoint(s) of evaluation of this end point: AEs will be discussed and recorded at every visit. Blood and urine samples for clinical chemistry, haematology, reproductive hormones and urinalysis (dipstick) parameters will be taken at the following timepoints: Screening, Cycle 1 (D1, D8, D15, D22), Cycle 2 (D1, D15) Cycle 3 onwards D1 of every cycle, treatment disc. and 28 day follow up. Blood pressure, heart rate, respiration rate and temperature will be recorded at the following timepoints: Screening, Cycle 1 – Every visit (D1, D2, D8, D15, D22,), Cycle 2 - Every visit (D1, D15), Cycle 3 onwards – D1 of every cycle and treatment disc. ECGs will be performed at the following timepoints: Screening, Cycle 1 – D1 pre-dose and 2 hrs post-dose, D8 pre-dose and 2hrs post dose, Cycle 2 onwards – D1 of every cycle, treatment disc. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To characterise the pharmacokinetics (PK) of CCS1477, following a single dose and at steady state after multiple dosing. To assess preliminary tumour response/activity of CCS1477 in patients with relapsed or refractory haem. malignancies (NHL, MM and AML/high-risk MDS). Anti-tumour activity defined by measurement of changes in: NHL - Radiological assessment, bone marrow disease status and serum immunoglobulins. MM - Blood/urine samples for myeloma response, bone/bone marrow disease status and serum immunoglobulins. AML - Bone marrow disease status. To obtain a preliminary assessment of CCS1477 by evaluation of overall survival (OS).;Timepoint(s) of evaluation of this end point: PK Blood C1D1, 2 & 3 (single dose) Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10, 24 -D2 & 48hr -D3 pre-dose C1 & C2 (multiple dose) Pre-dose, 0.5, 1, 1.5, 2, 4, 8, 10 & 24hr pre-dose NHL CT/MRI/FDG-PET: Scr, WK8, every 12wks until progression BM biopsy/aspirate: Scr, to confirm CR Serum Ig: Scr, as per disease guidelines MM Myeloma Response (blood/urine): Scr, C1D1, D1 of every cycle, disc. BM biopsy/aspirate: Scr, to confirm CR Serum Ig: Scr, C1D1, C3D1, C5D1, every 8 weeks Bone scan: Scr, to confirm CR AML BM biopsy/aspirate: Scr, C2D1, C4D1, C6D1 Peripheral blood Blast count and exploratory biomarkers: Scr, C1D1, D1 of every cycle, C7+ as clinically indicated OS until sufficient data collected | — |
Countries
France, Netherlands, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Trial Information
CellCentric Ltd
Outcome results
None listed