Ensayos clínicos

Inclusion Criteria:

• Provision of signed and dated, written informed consent prior to any study-specific procedures, sampling and analyses.
• Willing and able to participate in all required evaluations and procedures in this study protocol.
• Men and women ≥ 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2.
• Patients with confirmed (per standard disease specific diagnostic criteria), relapsed or refractory haematological malignancies (NHL, MM and AML). Patients will include:
  • B-cell non-Hodgkin lymphoma;
  • DLBCL, FL, MCL and Burkitt lymphoma;
  • Multiple myeloma;
  • AML/secondary AML (patients with acute promyelocytic leukemia (FAB subtype M3) will be excluded);
  • High-risk MDS; according to revised International Prognostic Scoring System (IPSS-R);
• Must have received standard 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. Patients must not require urgent cytoreductive therapy. .
  • NHL - at least two prior lines of systemic therapy; patients with indolent lymphomas must meet criteria for systemic therapy treatment;
  • MM patients must have exhausted or be ineligible for standard therapeutic options as available in the relevant geographical region;
  • AML – relapsed or refractory following standard therapeutic options (not candidates for curative therapies, such as allogeneic hematopoietic cell transplant or exhausted standard of care therapy available, which is likely to lead to disease remission according to the investigator), including non-intensive therapy and targeted agents, as applicable considering disease and patient characteristics as well as availability of therapy in the relevant geographical region;
  • High risk MDS patients must have previously failed treatment with at least 4 cycles of a hypomethylating agent.
• Adequate haematologic function defined as:
  • Absolute neutrophil count (ANC) ≥ 1000 cells/mm^3 (1.0 x 10^9/L);
  • Platelet count without requiring ongoing blood product support ≥ 75,000 cells/mm^3 (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 < 10,000/μl.
• Adequate organ function at screening defined as:
  • Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (ULN), or AST/ALT ≤ 5 x ULN (with underlying liver involvement following discussion with the medical monitor);
  • Total bilirubin ≤ 1.5 x ULN (or < 3 x ULN if bilirubin rise is due to Gilbert's syndrome or of non-hepatic origin, patients with borderline elevation due to underlying liver involvement may be eligible following discussion with the medical monitor);
  • Serum creatinine < 1.5 x ULN, OR creatinine clearance ≥ 50 mL/min as measured or calculated by Cockcroft and Gault equation, or ≥ 30 mL/min in patients with kidney function affected by the underlying malignancy;
  • Serum albumin > 2.5 g/dL.

Exclusion Criteria:

• 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;
  • Inhibitors of P-gp while on study treatment.
• Washout periods may be reduced for specific medications (e.g., 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.
• 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.
• Presence of, or history of, CNS lymphoma, symptomatic leptomeningeal disease, or spinal cord compression.
• 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 (e.g., hormonal therapy) is allowed.
• 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.
• Repeatable QTcF prolongation (> 480 msec).
• History of severe allergic or anaphylactic reactions or history of hypersensitivity to active or inactive excipients of CCS1477.
• Female patients who are pregnant or breast-feeding at study entry.
• 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.