2024-519498-20-00RecruitingPhase 2
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
Cellcentric Limited9 sites in 1 country16 target enrollmentStarted: April 29, 2025Last updated:
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Enrollment
- 16
- Locations
- 9
- Primary Endpoint
- The primary outcome measure for the study is: Safety and tolerability of CCS1477 as monotherapy and in combination.
Study Overview
Brief Summary
To investigate the safety and tolerability of CCS1477 when given as monotherapy and in combination in patients with blood/bone marrow cancers.
Eligibility Criteria
- Ages
- 18 years to 65+ years (65+ Years, 18-64 Years)
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Written informed consent
- •Females must agree to use highly effective contraceptive measures (if sexually active), must not be breast feeding & must have a negative serum pregnancy test prior to start of dosing if of child-bearing potential, or must have evidence of non-child-bearing potential by fulfilling one of the following criteria at screening: • Post-menopausal defined as aged more than 50 years & amenorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments. • Documentation of irreversible surgical sterilisation by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation. • Amenorrhoeic for 12 months & serum follicle-stimulating hormone, luteinizing hormone & plasma oestradiol levels in the postmenopausal range for the institution. Note: All patients receiving pomalidomide must fulfil the conditions of the Pregnancy Prevention Programme for pomalidomide Refer to the protocol for additional inclusion criteria for combination arms.
- •Willing&able to participate in all required evaluations and procedures
- •Men&women ≥18 years
- •Estado funcional ECOG ≤1
- •Patients with confirmed relapsed or refractory haematological malignancies (NHL, MM, AML & higher risk MDS). Patients will include: • B-cell non-Hodgkin lymphoma - DLBCL, FL, MCL & Burkitt lymphoma • T-cell non-Hodgkin lymphoma • Multiple myeloma o Patients must have measurable disease by IMWG criteria defined as either serum M protein ≥0.5g/dL, or urine ≥200mg/24h, or involved SFLC ≥ 10mg/dL with abnormal FLC ratio • AML/secondary AML (patients with acute promyelocytic leukemia (APL) (FAB subtype M3) will be excluded) • Higher-risk MDS; according to revised IPSS-R
- •Must have received standard therapy. Must not require urgent cytoreductive therapy • NHL- at least two prior lines of systemic therapy; patient should not be eligible for hematopoietic stem cell transplantation; DLBCL patients should have received, or waiting for, CAR T cell treatment, if eligible and available; patients with indolent lymphomas must meet criteria for systemic therapy treatment. Patients should not be eligible for allogenic transplantation. • MM patients (except Parts D3) must have exhausted or be ineligible for standard therapeutic options as available in the relevant geographical region. For Parts D3 - MM patients must have received at least 2 prior therapies including lenalidomide and a proteasome inhibitor. • AML–relapsed or refractory following standard therapeutic options, 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 • Higher-risk MDS patients must have previously failed treatment with at least 4 cycles of a hypomethylating agent (if applicable).
- •Adequate haematologic function • Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L) or ≥750 cells/mm3 in patients with Duffy null phenotype if this is considered their normal baseline • Platelet count without requiring ongoing blood product support ≥75,000 cells/mm3 (75 x 109/L), screening result should be independent of platelet transfusion for at least 3 days. • Haemoglobin level ≥80 g/L, screening Hb should be independent of transfusion support for at least 3 days. 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
- •Duration of the study & for 1 week after the last study medication administration (CCS1477 or combination agent), sexually active male patients must be willing to use barrier contraception i.e. condoms (with spermicide) with all sexual partners. Where the sexual partner is a 'woman of child-bearing potential' who is not using effective contraception, men must use a condom (with spermicide) & another form of contraception during the study & for 6 months after the last dose of study medication (CCS1477 or combination agent)
Exclusion Criteria
- •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. • Strong inducers of CYP3A4 taken within 4 weeks of the first dose of study treatment or whilst on study treatment • Strong inhibitors of CYP3A4, CYP2C8 substrates with a narrow therapeutic range, taken within 2 weeks of the first dose of study treatment or while on study treatment. The potent CYP3A4 inihibitor posaconazole is allowed in patients participating in the posaconazole DDI part of the study. Following review of the posaconazole DDI data, and with the agreement of the Safety Review Committee, concomitant use of posaconazole may be permitted thereafter in the study. • CYP3A4 sensitive substrates taken within 2 weeks of the first dose of study treatment & during Cycle 1, & should be avoided while on study treatment unless considered essential by the investigator, cannot be replaced, & agreed with the medical monitor. • Inhibitors of P-gp whilst on study treatment • 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 should be discontinued 5 half-lives prior to starting study treatment. Patients may receive fluvastatin or pravastatin (with monitoring for potential toxicities), or atorvastatin or simvastatin at 10mg daily dose only. • 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. • Steroids use >10mg daily (or 20mg daily for NHL) prednisolone or equivalent within 2 weeks of the first dose of study treatment. Replacement therapy steroids (even exceeding the above daily dose), given in the context of a transfusion, inhaled, nasal, topical and ophthalmic steroids are allowed. Note: For control of lymphoma related symptoms, patients may have received a brief (<7days) course of systemic steroids (≤ 100 mg prednisone equivalent per day) prior to initiation of study therapy. MM patients may receive >10mg daily if discussed and agreed with the medical monitor. • Major surgery within 4 weeks of the first dose of study treatment. • Shorter wash-out may be considered for some medications or palliative radiotherapy after discussion with medical monitor.
- •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.
- •Active or unresolved spinal cord compression or CNS infiltration.
- •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. Maintenance treatment is allowed.
- •Any evidence of severe or uncontrolled systemic disease (e.g. current unstable or uncompensated respiratory or cardiac conditions; recent history of significant cardiac incidents, eg. significant cardiac dysfunction (congestive heart failure [NY Heart Association Class III or IV]; myocardial infarction within 12 months of starting study; unstable or poorly controlled angina pectoris) or clinically significant arrhythmia; uncontrolled diabetes; history of, or active, bleeding diatheses; uncontrolled active systemic infection, including hepatitis B&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.
- •Repeatable QTcF prolongation (>480 msec).
- •History of severe allergic or anaphylactic reactions or any known severe allergies to any active or inactive ingredients in the study medications (CCS1477 and/or pomalidomide, dexamethasone, isatuximab, ixazomib, bortezomib, posaconazole, azacitidine or venetoclax as applicable).
- •Female patients who are pregnant or breast-feeding at any time during the study.
- •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. Refer the protocol for additional exclusion criteria for combination arms.
Outcomes
Primary Outcomes
The primary outcome measure for the study is: Safety and tolerability of CCS1477 as monotherapy and in combination.
The primary outcome measure for the study is: Safety and tolerability of CCS1477 as monotherapy and in combination.
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.
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.
Secondary Outcomes
- To characterise the pharmacokinetics (PK) of CCS1477, following a single dose and at steady state after multiple dosing as monotherapy and in combination.
- To assess preliminary tumour response/activity of CCS1477 in patients with relapsed or refractory haem. malignancies (NHL, MM and AML/higher-risk MDS).
- Anti-tumour activity defined by measurement of changes in: - NHL - Radiological assessment, bone marrow disease status and serum immunoglobulins and Tumour biopsy. -MM - Blood/urine samples for myeloma response, bone/bone marrow disease status and serum immunoglobulins. -AML and MDS - Bone marrow disease status.
- To obtain a preliminary assessment of CCS1477 by evaluation of overall survival (OS).
Investigators
Tomasz Knurowski
Scientific
Cellcentric Limited
Study Sites (9)
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