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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT04810611
Registration number
NCT04810611
Ethics application status
Date submitted
9/03/2021
Date registered
23/03/2021
Date last updated
17/05/2024
Titles & IDs
Public title
Phase Ib Study of Select Drug Combinations in Patients With Lower Risk MDS
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Scientific title
A Phase Ib, Multicenter, Open-label Platform Study of Select Drug Combinations in Adult Patients With Lower Risk (Very Low, Low, or Intermediate Risk) Myelodysplastic Syndrome
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Secondary ID [1]
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2019-004623-21
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Secondary ID [2]
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CMBG453E12101
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Universal Trial Number (UTN)
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Trial acronym
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes
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Condition category
Condition code
Blood
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Haematological diseases
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Blood
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Other blood disorders
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Other
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Research that is not of generic health relevance and not applicable to specific health categories listed above
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - MBG453
Treatment: Drugs - NIS793
Treatment: Drugs - canakinumab
Experimental: Arm 1: MBG453 single agent - Treatment with MBG453 single agent Q4W to confirm safety and tolerability of RD.
Experimental: Arm 2: NIS793 single agent - Treatment with NIS793 single agent Q3W to establish RD in this indication and confirm safety and tolerability.
Experimental: Arm 3: canakinumab single agent - Treatment with single agent canakinumab Q4W to confirm safety and tolerability of RD.
Experimental: Arm 4: MBG453 + NIS793 combination - Treatment with combination of MBG453 and NIS793 Q3W to confirm safety and tolerability of combination RD.
Experimental: Arm 5: MBG453 + canakinumab combination - Treatment with MBG453 + canakinumab combination Q4W to confirm safety and tolerability of combination RD.
Treatment: Drugs: MBG453
Anti-TIM3 monoclonal antibody
Treatment: Drugs: NIS793
Anti-TGF-ß monoclonal antibody
Treatment: Drugs: canakinumab
Anti-IL-1ß monoclonal antibody
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Intervention code [1]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Dose interruption reduction
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Assessment method [1]
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Dose tolerability
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Timepoint [1]
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30 Months
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Primary outcome [2]
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Incidence of DLTs
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Assessment method [2]
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Incidence of dose limiting toxicities (DLTs) during the first 2 cycle of treatment during the dose escalation/confirmation part
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Timepoint [2]
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30 Months
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Primary outcome [3]
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Dose intensity
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Assessment method [3]
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Dose tolerability
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Timepoint [3]
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30 Months
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Primary outcome [4]
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AE and SAE incidence
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Assessment method [4]
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Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) as per CTCAE v5.0, by treatment
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Timepoint [4]
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30 months
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Secondary outcome [1]
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Reduction in red blood cell (RBC) / platelet transfusions from baseline in transfusion dependent patients
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Assessment method [1]
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The number of red cell or platelet transfusions a patient receives over the course of study treatment will be compared to the patient's baseline transfusion requirements based on the number of transfusions received during the 16-weeks period prior to the start of study treatment.
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Timepoint [1]
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Baseline, 30 Months
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Secondary outcome [2]
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Duration of transfusion independence lasting for >=8 weeks, >=12 weeks, >=16 weeks, >=24 weeks in transfusion dependent patients
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Assessment method [2]
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Red cell or platelet transfusion independence is defined as no red cell or platelet transfusions with a duration lasting for 8, 12, 16, or 24 weeks.
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Timepoint [2]
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30 Months
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Secondary outcome [3]
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Change from baseline in hemoglobin (Hb) in transfusion dependent and transfusion independent patients
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Assessment method [3]
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Hemoglobin levels over the course of the study will be compared to the patient's baseline level to monitor for improvements in anemia.
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Timepoint [3]
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Baseline, 30 Months
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Secondary outcome [4]
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Change from baseline in platelet count in transfusion dependent and transfusion independent patients
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Assessment method [4]
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Platelet count over the course of the study will be compared to the patient's baseline count to monitor for improvements in thrombocytopenia.
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Timepoint [4]
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Baseline, 30 Months
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Secondary outcome [5]
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Change from baseline in Absolute Neutrophil Count/White Blood Cells (ANC/WBC) in transfusion dependent and transfusion independent patients
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Assessment method [5]
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Platelet count over the course of the study will be compared to the patient's baseline count to monitor for improvements in thrombocytopenia.
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Timepoint [5]
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Baseline, 30 Months
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Secondary outcome [6]
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Best Overall Response (BOR) in transfusion dependent and transfusion independent patients
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Assessment method [6]
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BOR is the best disease response recorded from the start of the treatment until disease progression/relapse. The subject's BOR will be calculated based on investigator's response evaluations per International Working Group (IWG) criteria.
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Timepoint [6]
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30 Months
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Secondary outcome [7]
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Time to onset of transfusion independence in transfusion dependent patients
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Assessment method [7]
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Time to onset of either red cell transfusion independence or platelet transfusion independence.
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Timepoint [7]
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30 Months
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Secondary outcome [8]
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Time to onset of BOR in transfusion dependent and transfusion independent patients
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Assessment method [8]
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Time to onset of BOR is defined as the time between date of start of study treatment to the date of first onset of Partial Response (PR) or better response.
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Timepoint [8]
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30 Months
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Secondary outcome [9]
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Duration of Response (DOR) in transfusion dependent and transfusion independent patients
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Assessment method [9]
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DOR is defined as the duration from the first documented onset of complete response (CR), complete remission with partial hematologic recovery (CRh), bone marrow CR (mCR) or PR to the date of disease progression (PD) or relapse or death due to myelodysplastic syndrome (MDS).
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Timepoint [9]
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30 Months
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Secondary outcome [10]
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Overall Response Rate (ORR) in transfusion dependent and transfusion independent patients
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Assessment method [10]
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ORR is the proportion of subjects with a best overall response of either CR or CRh, or mCR or PR.
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Timepoint [10]
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30 Months
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Secondary outcome [11]
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Progression free survival (PFS) in transfusion dependent and transfusion independent patients
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Assessment method [11]
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PFS is defined as the time from the start of treatment until death due to any reason, disease progression, or relapse, whichever comes first.
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Timepoint [11]
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30 Months
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Secondary outcome [12]
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Time to progression (TTP) in transfusion dependent and transfusion independent patients
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Assessment method [12]
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TTP is the time from the start of treatment to the date of PD, relapse or death due to underlying cancer.
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Timepoint [12]
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30 Months
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Secondary outcome [13]
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Characterize pharmacokinetics for single agents and combinations: Cmax
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Assessment method [13]
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Serum concentrations and derived PK parameters
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Timepoint [13]
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30 Months
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Secondary outcome [14]
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Characterize pharmacokinetics for single agents and combinations: Tmax
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Assessment method [14]
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Serum concentrations and derived PK parameters
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Timepoint [14]
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30 Months
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Secondary outcome [15]
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Characterize pharmacokinetics for single agents and combinations: Ctrough
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Assessment method [15]
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Serum concentrations and derived PK parameters
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Timepoint [15]
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30 Months
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Secondary outcome [16]
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Characterize the prevalence of immunogenicity
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Assessment method [16]
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Anti-drug antibody prevalence at baseline and on treatment.
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Timepoint [16]
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30 Months
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Eligibility
Key inclusion criteria
Key
1. Signed informed consent must be obtained prior to participation in the study.
2. Patients must be = 18 years of age at the time of signing the informed consent form
(ICF).
3. Patients must have a diagnosis prior to participation in the study of IPSS-R very low,
low, or intermediate risk MDS with =10% bone marrow blasts and one or more of the
following:
1. Symptomatic anemia with hemoglobin <10 g/dL that has relapsed after or is
refractory to ESAs (or the patient is intolerant to ESAs)
2. Symptomatic anemia with hemoglobin <10 g/dL) that is ESA-naive with EPO level =
500 /uL
3. Thrombocytopenia with platelets <30,000/uL or with clinically significant
bleeding or bruising and platelets <50,000/uL
4. Neutropenia with an absolute neutrophil count (ANC) <500/ µL or with recurrent
and/or severe infections and an ANC that is <1000/ µL and amenable to response
assessments by International Working Group (IWG) response criteria in
myelodysplasia (Cheson et al 2006)
4. Patients who are refractory to, intolerant of, or ineligible/unable to receive SOC
therapeutic options including lenalidomide
5. Eastern Cooperative Oncology Group (ECOG) performance status (PS) =2
6. Patient must be a candidate for serial bone marrow aspirate and/or biopsy according to
the institutions' guidelines and be willing to undergo a bone marrow aspirate and/or
biopsy at screening, during and at the end of therapy on this study -
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Minimum age
18
Years
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Maximum age
No limit
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Sex
Both males and females
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Can healthy volunteers participate?
No
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Key exclusion criteria
1. Systemic antineoplastic therapy (including cytotoxic chemotherapy, alpha-interferon,
kinase inhibitors or other targeted small molecules, and toxin-immunoconjugates) or
any experimental therapy within 14 days or 5 half-lives, whichever is longer, before
the first dose of study treatment.
2. History of hypersensitivity to any of the study treatments or its excipients or to
drugs of similar chemical classes.
3. Patients with chronic myelomonocytic leukemia (CMML) or
myelodysplastic/myeloproliferative neoplasms (MDS/MPN)
4. Use of hematopoietic colony-stimulating growth factors (e.g. G-CSF, GM-CSF, M-CSF),
thrombopoietin mimetics or ESAs anytime = 2 weeks (or 5 half-lives, whichever is
longer) prior to start of study treatment.
5. Systemic chronic corticosteroid therapy (>10 mg/day prednisone or equivalent) or any
immunosuppressive therapy within 7 days of first dose of study treatment. Topical,
inhaled, nasal and ophthalmic steroids are allowed.
6. For arms containing canakinumab: Patients with ANC < 500 /µL
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Study design
Purpose of the study
Treatment
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Allocation to intervention
Non-randomised trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Open (masking not used)
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Who is / are masked / blinded?
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 1
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Terminated
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
18/06/2021
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
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Actual
19/04/2024
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Sample size
Target
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Accrual to date
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Final
33
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Recruitment in Australia
Recruitment state(s)
VIC
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Recruitment hospital [1]
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Novartis Investigative Site - Prahran
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Recruitment postcode(s) [1]
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3181 - Prahran
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Recruitment outside Australia
Country [1]
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United States of America
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State/province [1]
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California
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United States of America
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State/province [2]
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Florida
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United States of America
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State/province [3]
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Massachusetts
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Country [4]
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United States of America
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Ohio
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Country [5]
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United States of America
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Texas
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Country [6]
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Israel
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State/province [6]
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Tel Aviv
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Country [7]
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Italy
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State/province [7]
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MI
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Country [8]
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Korea, Republic of
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State/province [8]
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Seoul
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Country [9]
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Singapore
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State/province [9]
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Singapore
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Country [10]
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Spain
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State/province [10]
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Castilla Y Leon
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Country [11]
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Spain
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State/province [11]
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Catalunya
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Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
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Name
Novartis Pharmaceuticals
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Address
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Country
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Ethics approval
Ethics application status
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Summary
Brief summary
The purpose of this study was to characterize the safety, tolerability and confirm the dose
for select single agents and combinations in patients with lower risk (very low, low, and
intermediate risk) MDS.
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Trial website
https://clinicaltrials.gov/ct2/show/NCT04810611
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Address
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Phone
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Fax
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Email
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Contact person for public queries
Name
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Address
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Phone
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Fax
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Email
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT04810611
Download to PDF