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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/study/NCT05456269
Registration number
NCT05456269
Ethics application status
Date submitted
4/07/2022
Date registered
13/07/2022
Titles & IDs
Public title
A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS
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Scientific title
An Open-label Two Strata Study of Bisantrene in Combination With Cytarabine Arabinoside or Bisantrene in Combination With Oral Decitabine/Cedazuridine for the Treatment of Acute Myeloid Leukemia Patients With Extramedullary Disease
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Secondary ID [1]
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RAC-006
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Universal Trial Number (UTN)
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Trial acronym
BISECT
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia
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Recurrent Acute Myeloid Leukemia
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Refractory Acute Myeloid Leukemia
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0
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Higher Risk Myelodysplastic Syndrome
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0
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Chronic Myelomonocytic Leukemia
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0
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Condition category
Condition code
Cancer
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0
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Leukaemia - Acute leukaemia
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Cancer
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0
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0
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Leukaemia - Chronic leukaemia
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Cancer
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0
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Children's - Leukaemia & Lymphoma
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Blood
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0
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Haematological diseases
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Blood
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0
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Other blood disorders
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Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Treatment: Drugs - Bisantrene Dihydrochloride (high dose)
Treatment: Drugs - Bisantrene Dihydrochloride (low dose)
Treatment: Drugs - Cytarabine Hydrochloride
Treatment: Drugs - Decitabine and cedazuridine
Experimental: Stratum 1 - Bisantrene infused daily for 7 days of induction cycle 1; followed by bisantrene infusion on Days 1 and 2 and cytarabine arabinoside continuous infusion on Days 1 to 5 of each consolidation cycle for up to 3 cycles.
Each cycle is 28 days, with a potential to expand to 42 days to allow for full hematologic recovery.
Experimental: Stratum 2 - Decitabine/cedazuridine daily on Days 1-5, Bisantrene infusion on Days 3 and 5 in 28 day cycle. Treatment repeats every 28 days up to 12 cycles in the absence of disease progression or unacceptable toxicity.
Each has potential to expand to 42 days to allow for full hematologic recovery.
Treatment: Drugs: Bisantrene Dihydrochloride (high dose)
Induction monotherapy cycle: IV bisantrene daily on Days 1 to 7, starting at 250 mg/m2 then adjusted to either 275 mg/m2 or 225 mg/m2 based on confirmed dose (Run-in) Consolidation combination cycle/s: IV bisantrene daily on Days 1 to 2
Treatment: Drugs: Bisantrene Dihydrochloride (low dose)
IV bisantrene at escalating doses for 3 dose levels of 50, 65, 85 mg/m2 on Days 3 and 5 until Maximum tolerated dose (MTD) reached.
Treatment: Drugs: Cytarabine Hydrochloride
Consolidation cycles: continuous IV cytarabine (100mg/m2) on Days 1 to 5
Treatment: Drugs: Decitabine and cedazuridine
PO fixed-dose decitabine/cedazuridine 35/100 mg tablet daily for 5 days (Days 1 to 5), 1 hour prior bisantrene infusion
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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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Stratum 1, Stage 1: Dose confirmation
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Assessment method [1]
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Maximum tolerated dose (MTD) based on occurence dose limiting toxicity (DLT) graded according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE) for Adverse Events v5.0 after completion of 2 cycles of treatment
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Timepoint [1]
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8 weeks
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Primary outcome [2]
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Stratum 1 Stage 2: Overall response
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Assessment method [2]
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Morphological overall response, defined as complete remission (CR), CR with incomplete hematologic recovery or morphologic leukemia free state (MLFS), after completion of first treatment cycle 1
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Timepoint [2]
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4 weeks
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Primary outcome [3]
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Stratum 2: Safety and tolerabillity
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Assessment method [3]
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Assessed based on the occurence of non-hematological Dose limiting toxicity (DLT) as graded according to the National Cancer Institute Common Terminology Criteria (NCI CTCAE) for Adverse Events v5.0 at the completion of cycle 1.
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Timepoint [3]
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4 weeks
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Secondary outcome [1]
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Stratum 1: Minimal Residual Disease (MRD) response
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Assessment method [1]
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Response is defined as MRD negativity with and without morphological complete remission (CR), at low level molcular MRD with CR and MRD relapse (coversion MRD negativity to positivity) at the completion of cycle 1
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Timepoint [1]
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4 weeks
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Secondary outcome [2]
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Stratum 1: Radiologic response
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Assessment method [2]
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Response evaluation by 18F-FDG-PET/CT is based on the 5-point scale Deauville criteria for complete metabolic response (defined as Deauville Score (DS) 1, 2, or 3) or for partial metabolic response (defined DS of 4 or 5 with decrease in number or activity in bone marrow/EMD disease at the completion of cycles 1,2 and 4..
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Timepoint [2]
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4, 8 and 16 weeks
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Secondary outcome [3]
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Stratum 1: Dermal clinical response
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Assessment method [3]
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Dermal response based on improvement on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as decrease of at least two points relative to baseline at the completion of cycles 1,2 3 and 4.
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Timepoint [3]
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4, 8, 12, and 16 weeks
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Secondary outcome [4]
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Stratum 1: Dermal therapeutic response
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Assessment method [4]
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Dermal therapeutic improvement based on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as decrease of at least two points relative to baseline at the completion of cycles 1,2 3 and 4.
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Timepoint [4]
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4, 8, 12, and 16 weeks
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Secondary outcome [5]
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Stratum 1: Safety and tolerability
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Assessment method [5]
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Safety and tolerability based on the incidence and severity of adverse events assessed using National Cancer Institute-Common Terminology Criteria for Adverse Events \[NCI-CTCAE\] v5.0, grade per event, patient, and cycle of treatment.
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Timepoint [5]
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4, 8, 12 and 16 weeks
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Secondary outcome [6]
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Stratum 1: Number of participants that recieve subsequent allogeneic hematopoietic stem cell transplant
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Assessment method [6]
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Proportion of patients who receive subsequent allogeneic HSCT
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Timepoint [6]
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5 years
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Secondary outcome [7]
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Stratum 1:Event free survival (EFS)
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Assessment method [7]
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EFS assessed between treatment start until the date of the earliest of these events: death, progression or off protocol-treatment for any reason using the Kaplan-Meier method
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Timepoint [7]
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Day 1 (treatment start) to 5 years
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Secondary outcome [8]
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Stratum 1: Overall Survival (OS)
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Assessment method [8]
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OS assessed between treatment start until death due to any cause using the Kaplan-Meier method
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Timepoint [8]
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Day 1 (treatment start) to 5 years
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Secondary outcome [9]
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Stratum 2: Overall response
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Assessment method [9]
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Morphological overall response, defined as either CR or CR as complete remission (CR), CR with incomplete hematologic recovery, CR with incomplete count recovery or MLFS. For patients with MDS/CMML, overall response, defined as either CR or modified CR mCR with haematological improvement (HI) at the end of cycle 1
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Timepoint [9]
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4 weeks
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Secondary outcome [10]
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Stratum 2: Minimal Residual Disease (MRD) response
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Assessment method [10]
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Response is defined as MRD negativity with and without morphological complete remission (CR), at low level molecular MRD with CR and MRD relapse (coversion MRD negativity to positivity) at the completion of cycle 4.
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Timepoint [10]
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16 weeks
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Secondary outcome [11]
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Stratum 2: Radiologic response
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Assessment method [11]
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Response evaluation by 18F-FDG-PET/CT, based on the 5-point scale Deauville criteria for complete metabolic response (defined as as Deauville Score (DS) 1, 2, or 3) or for partial metabolic response (defined as DS of 4 or 5 with decrease in number or activity in bone marrow/EMD disease) at the the completion of cycles 4, 6, 9 and 12
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Timepoint [11]
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16, 36 and 48 weeks
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Secondary outcome [12]
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Stratum 2: Dermal clinical response
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Assessment method [12]
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Dermal clinical improvement based on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as as disease severity score of 1 (almost clear) or 0 (clear) and at least a two grade/point decrease in severity score relative to baseline the completion of cycles 4, 6, 9 and 12
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Timepoint [12]
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4, 24, 36 and 48 weeks
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Secondary outcome [13]
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Stratum 2: Dermal therapeutic response
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Assessment method [13]
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Dermal therapeutic improvement based on the static investigator global assessment (IGA) 5-point disease severity scores, where higher score indicate more disease, defined as decrease of at least two points relative to baseline the completion of cycles 4, 6, 9 and 12.
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Timepoint [13]
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4, 24, 36 and 48 weeks
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Secondary outcome [14]
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Stratum 2: Event free survival (EFS)
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Assessment method [14]
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EFS assessed between treatment start until the date of the earliest of these events: death, progression or off protocol-treatment for any reason assessed
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Timepoint [14]
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Day 1 (treatment start) up to 5 years
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Secondary outcome [15]
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Stratum 2: Overall survival (OS)
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Assessment method [15]
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OS assessed between treatment start until death due to any cause using the Kaplan-Meier method
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Timepoint [15]
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Day 1 (treatment start) to 5 years
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Eligibility
Key inclusion criteria
[Both Stratums]
1. Patients must be able to understand and provide informed written consent.
2. Patients must be of age = 18 years at the time of signing the informed consent.
3. Extramedullary disease (i.e., AML) by 18F-FDG PET/CT and/or clinical morphology (histopathology of chloroma, leukemia cutis or AML) at pre-screening
4. Patients who have undergone stem cell transplantation (SCT), maybe included if they are = 8 weeks from stem cell infusion (autologous or allogeneic), have no active graft versus host disease (GVHD), are off immune suppression for at least 2 weeks, and do not have a history of veno occlusive disease (VOD).
5. Eastern Cooperative Oncology Group (ECOG) performance status = 2.0 for intensive Stratum 1 patients and = 3.0 for low intensity treatment Stratum 2 patients.
6. Life expectancy estimated to be > 3 months.
7. Adequate organ function as evidenced by serum total bilirubin = 2.0 mg/dL, alanine aminotransferase (ALT) or aspartate aminotransferase (AST) = 5 × the upper limit of normal (ULN), serum creatinine = 1.5 mg/dL or calculated creatinine clearance of = 60 mL/min.
8. Cardiac ejection fraction = 50%, assessed by 2-Dimensional (2D) echocardiogram.
9. Females of childbearing potential must have a negative serum pregnancy test at enrolment or within 14 days before study entry and must agree to use an adequate method of contraception, i.e., barrier method, during the study until 30 days after the last treatment. Males must be surgically or biologically sterile or agree to use an adequate method of contraception, i.e., barrier method, during the study until 30 days after the last treatment.
[Stratum 1 only]
10. Diagnosis of R/R AML, defined as = 5% blasts in a patient with known prior history of AML according to World Health Organization (WHO) criteria. Patients with AML that have relapsed at least once or are primary induction failure will be eligible.
[Stratum 2 only]
11. Patients with diagnosis of de novo AML with EMD, or R/R AML with EMD.
12. Patients with MDS or CMML, diagnosed according to the 2016 WHO classification with high-risk disease per the International Prognostic Scoring System (IPSS) of intermediate 2 or higher for both MDS and CMML. Revised IPSS intermediate risk patients can be considered after discussion with the Investigator.
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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
[Both Stratums]
1. Acute promyelocytic leukemia (APML) M3 subtype of AML.
2. Central nervous system manifestations of AML, unless treated and with no residual manifestations (either by cerebrospinal fluid (CSF) cytology, radiologically or by other clinical assessments) in the last 2 weeks.
3. Evidence or recent history of CNS disease, including primary or metastatic brain tumors, seizure disorders unless there is evidence for clearance of CNS leukemia (2 leukemia free CSFs by morphology and /or flow cytometry 1 week apart).
4. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, cirrhosis, chronic obstructive or restrictive pulmonary disease, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia.
5. Other active malignancy (including other hematologic malignancies) or other malignancy within the last 12 months except non-melanoma skin cancer or cervical intraepithelial neoplasia.
6. Major surgery within 4 weeks of treatment.
7. Any medical, psychological, or social condition that may interfere with study patient or compliance or may compromise the patient's safety in the opinion of the Investigator.
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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
Other
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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
Withdrawn
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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
29/07/2022
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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
31/08/2023
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Sample size
Target
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Accrual to date
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Final
0
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Recruitment in Australia
Recruitment state(s)
NSW
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Recruitment hospital [1]
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Calvary Mater - Newcastle
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Recruitment postcode(s) [1]
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2298 - Newcastle
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Funding & Sponsors
Primary sponsor type
Commercial sector/industry
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Name
Race Oncology Ltd
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Address
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Country
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Other collaborator category [1]
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Commercial sector/industry
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Name [1]
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Astex Pharmaceuticals, Inc.
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Address [1]
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Country [1]
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0
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Ethics approval
Ethics application status
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Summary
Brief summary
This is a two strata Phase 1b study to assess the safety and efficacy of bisantrene (RC110) in combination with a) cytarabine arabinoside (Ara-C) treatment for patients with relapsed or refractory (R/R) Acute Myeloid Leukemia (AML) with extramedullary disease and able to tolerate intensive chemotherapy; b) in combination with decitabine/cedazuridune (ASTX727) new or relapsed or refractory AML or high risk MDS or CMML with extramedullary disease and unable or not willing to have intensive chemotherapy.
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Trial website
https://clinicaltrials.gov/study/NCT05456269
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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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Marinella Messina, PhD
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Address
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Clinical Director
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Country
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Phone
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Fax
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0
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Email
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0
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Contact person for public queries
Name
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0
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Address
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0
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Country
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0
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Phone
0
0
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Fax
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0
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Email
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Contact person for scientific queries
Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
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No/undecided IPD sharing reason/comment
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What supporting documents are/will be available?
No Supporting Document Provided
Results publications and other study-related documents
No documents have been uploaded by study researchers.
Results not provided in
https://clinicaltrials.gov/study/NCT05456269