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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/NCT05456269




Registration number
NCT05456269
Ethics application status
Date submitted
4/07/2022
Date registered
13/07/2022
Date last updated
3/10/2023

Titles & IDs
Public title
A Study of Bisantrene Combined With Cytarabine or With Decitabine for Adult Subjects With Extramedullary AML and MDS
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
Secondary ID [1] 0 0
RAC-006
Universal Trial Number (UTN)
Trial acronym
BISECT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Acute Myeloid Leukemia 0 0
Recurrent Acute Myeloid Leukemia 0 0
Refractory Acute Myeloid Leukemia 0 0
Higher Risk Myelodysplastic Syndrome 0 0
Chronic Myelomonocytic Leukemia 0 0
Condition category
Condition code
Cancer 0 0 0 0
Leukaemia - Acute leukaemia
Cancer 0 0 0 0
Leukaemia - Chronic leukaemia
Cancer 0 0 0 0
Children's - Leukaemia & Lymphoma
Blood 0 0 0 0
Haematological diseases
Blood 0 0 0 0
Other blood disorders

Intervention/exposure
Study type
Interventional
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
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Stratum 1, Stage 1: Dose confirmation
Timepoint [1] 0 0
8 weeks
Primary outcome [2] 0 0
Stratum 1 Stage 2: Overall response
Timepoint [2] 0 0
4 weeks
Primary outcome [3] 0 0
Stratum 2: Safety and tolerabillity
Timepoint [3] 0 0
4 weeks
Secondary outcome [1] 0 0
Stratum 1: Minimal Residual Disease (MRD) response
Timepoint [1] 0 0
4 weeks
Secondary outcome [2] 0 0
Stratum 1: Radiologic response
Timepoint [2] 0 0
4, 8 and 16 weeks
Secondary outcome [3] 0 0
Stratum 1: Dermal clinical response
Timepoint [3] 0 0
4, 8, 12, and 16 weeks
Secondary outcome [4] 0 0
Stratum 1: Dermal therapeutic response
Timepoint [4] 0 0
4, 8, 12, and 16 weeks
Secondary outcome [5] 0 0
Stratum 1: Safety and tolerability
Timepoint [5] 0 0
4, 8, 12 and 16 weeks
Secondary outcome [6] 0 0
Stratum 1: Number of participants that recieve subsequent allogeneic hematopoietic stem cell transplant
Timepoint [6] 0 0
5 years
Secondary outcome [7] 0 0
Stratum 1:Event free survival (EFS)
Timepoint [7] 0 0
Day 1 (treatment start) to 5 years
Secondary outcome [8] 0 0
Stratum 1: Overall Survival (OS)
Timepoint [8] 0 0
Day 1 (treatment start) to 5 years
Secondary outcome [9] 0 0
Stratum 2: Overall response
Timepoint [9] 0 0
4 weeks
Secondary outcome [10] 0 0
Stratum 2: Minimal Residual Disease (MRD) response
Timepoint [10] 0 0
16 weeks
Secondary outcome [11] 0 0
Stratum 2: Radiologic response
Timepoint [11] 0 0
16, 36 and 48 weeks
Secondary outcome [12] 0 0
Stratum 2: Dermal clinical response
Timepoint [12] 0 0
4, 24, 36 and 48 weeks
Secondary outcome [13] 0 0
Stratum 2: Dermal therapeutic response
Timepoint [13] 0 0
4, 24, 36 and 48 weeks
Secondary outcome [14] 0 0
Stratum 2: Event free survival (EFS)
Timepoint [14] 0 0
Day 1 (treatment start) up to 5 years
Secondary outcome [15] 0 0
Stratum 2: Overall survival (OS)
Timepoint [15] 0 0
Day 1 (treatment start) to 5 years

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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
29/07/2022
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
31/08/2023
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Calvary Mater - Newcastle
Recruitment postcode(s) [1] 0 0
2298 - Newcastle

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Race Oncology Ltd
Address
Country
Other collaborator category [1] 0 0
Commercial sector/Industry
Name [1] 0 0
Astex Pharmaceuticals, Inc.
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

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.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05456269
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Marinella Messina, PhD
Address 0 0
Clinical Director
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05456269