Clinical trial NCT05883956: A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia
Official title: A Phase 3b, Randomized, Open-Label, Double Crossover Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Adult Patients With IPSS R Intermediate Myelodysplastic Syndrome, Low Blast Acute Myeloid Leukemia, IPSS Intermediate-2 or High Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Myelodysplastic Syndromes
Leukemia, Myeloid, Acute
Leukemia, Myelomonocytic, Chronic
Patient Preference
Lead sponsor: Otsuka Australia Pharmaceutical Pty Ltd
Sponsor class: INDUSTRY
First posted: 2023-06-01
Enrollment: 13
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: It is hypothesized that significantly more patients would prefer oral decitabine/cedazuridine to subcutaneous (SC) azacitidine (AZA) due to several factors, including improved treatment convenience, the reduced risk of nosocomial infections, and reduced treatment discomfort. However, this hypothesis has not been formally studied in a controlled setting. This study aims to address this evidence gap and evaluate patient, primary caregiver (carer), and clinician treatment preference between oral decitabine/cedazuridine and SC AZA in the treatment of adult patients with International Prognostic Scoring System-Revised (IPSS-R) intermediate, IPSS intermediate-2, or high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukemia (CMML), or low-blast (LB) acute myeloid leukemia (AML) and thereby lend further credibility to the clinical, economic, and patient value of oral decitabine/cedazuridine.


Eligibility criteria: Inclusion Criteria:

For Patients:

Patients are eligible to be included in the study only if all of the following criteria apply at any time starting from Screening up to Day 1 prior to study treatment administration:

* Patients must be 18 years of age or older.
* IPSS-R defined intermediate MDS, IPSS defined intermediate 2 or high-risk MDS, LB AML or CMML (with symptoms), as confirmed by recent full blood examination, bone marrow biopsy, and cytogenetic testing. NOTE: IPSS-R defined intermediate MDS patients are limited to less than 50% of enrolled patients.
* Life expectancy of at least 6 months.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 inclusive.
* Patient must be able to co-operate and complete tasks (including tasks such as electronic questionnaires on digital devices) over the following 4 months.

Inclusion Criteria:

For Patients:

Patients are eligible to be included in the study only if all of the following criteria apply at any time starting from Screening up to Day 1 prior to study treatment administration:

* Patients must be 18 years of age or older.
* IPSS-R defined intermediate MDS, IPSS defined intermediate 2 or high-risk MDS, LB AML or CMML (with symptoms), as confirmed by recent full blood examination, bone marrow biopsy, and cytogenetic testing. NOTE: IPSS-R defined intermediate MDS patients are limited to less than 50% of enrolled patients.
* Life expectancy of at least 6 months.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 to 2 inclusive.
* Patient must be able to co-operate and complete tasks (including tasks such as electronic questionnaires on digital devices) over the following 4 months.
* Patient must be able to identify a carer to participate in completing the cTPMQ.

For Carers:

• Primary carer of a patient meeting all of the inclusion criteria (ie, a patient who meets criteria defined above).

For Clinicians:

• Clinician treating patients meeting all of the inclusion criteria (ie, treats patients who meet criteria defined above).

Exclusion Criteria:

For Patients:

Patients are excluded from the study if any of the following criteria apply:

* Patients with known hypersensitivity to the study treatments oral decitabine/cedazuridine or azacitidine.
* Patients with advanced malignant hepatic tumors.
* Patients with severe renal impairment (creatinine clearance \<30 mL/min).
* Patients who have received hypomethylating agents (HMA) previously.
* Patients who are receiving lenalidomide or are receiving other therapies outside of standard of care (SOC).
* Receipt of any immunotherapy, any conventional or investigational systemic anti-cancer therapy within 5 half-lives of the drug, or within 4 weeks prior to the first dose of study treatment (whichever is longer).
* Any medical, psychological, social, or other condition which in the view of the Investigator is likely to interfere with the study, compliance, or put the patient at risk.
* Participants who are not fluent in English, or who cannot read or write in English will be excluded from the study.

For Carers:

Carers are excluded from the study if any of the following criteria apply:

* They are a carer of a patient who meets any of the exclusion criteria listed above.
* They are a relative of an employee of the investigational clinic or sponsor (e.g. Investigator, study coordinator)

For Clinicians:

• Clinicians will be excluded from participating in the study if they are a relative of an employee of the investigational clinic or sponsor (e.g. Investigator, Study Coordinator).

Primary outcomes:
measure: Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the patient treatment preference in myelodysplasia questionnaire (pTPMQ)
timeFrame: Prior to initiation of Cycle 3 (each cycle is 28 days)
measure: Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the pTPMQ
timeFrame: Prior to initiation of Cycle 5 (each cycle is 28 days)
Secondary outcomes:
measure: Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the carer treatment preference in myelodysplasia questionnaire (cTPMQ)
timeFrame: Prior to initiation of Cycle 3 (each cycle is 28 days)
measure: Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the cTPMQ
timeFrame: Prior to initiation of Cycle 5 (each cycle is 28 days)
measure: Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the medical treatment preference in myelodysplasia questionnaire (mTPMQ)
timeFrame: Prior to initiation of Cycle 4 (each cycle is 28 days)
measure: Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the mTPMQ
timeFrame: End of Study (EOS) Day 28
measure: Proportion of clinicians choosing oral decitabine/cedazuridine vs subcutaneous azacitidine for continuation of treatment and reasons for the treatment choice based on the mTPMQ
timeFrame: Cycle 5, Day 1 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EQ-5D-5L in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 1, Day 1 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EORTC QLQ-C30 in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 1, Day 1 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EQ-5D-5L in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 3, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EORTC QLQ-C30 in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 3, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and Subcutaneous azacitidine as assessed using the EQ-5D-5L in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 4, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and Subcutaneous azacitidine as assessed using the EORTC QLQ-C30 in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 4, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EQ-5D-5L in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 5, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EORTC QLQ-C30 in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 5, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EQ-5D-5L in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 6, Day 5 (each cycle is 28 days)
measure: Difference in quality of life between oral decitabine/cedazuridine and subcutaneous azacitidine as assessed using the EORTC QLQ-C30 in Myelodysplastic Syndrome, Chronic Myelomonocytic Leukemia and Low-Blast Acute Myeloid Leukemia patients
timeFrame: Cycle 6, Day 5 (each cycle is 28 days)
measure: The difference in the incidence of treatment discontinuation and reasons for treatment discontinuation
timeFrame: Baseline (pre-intervention) through to study completion (up to 6 cycles of treatment where each cycle is 28 days)
measure: Incidence and severity of adverse events upon study physician discretion.
timeFrame: Baseline (pre-intervention) through to study completion (up to 6 cycles of treatment where each cycle is 28 days)
Other outcomes:
Locations:
city: Newcastle
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Benowa
country: Australia
facility: Pindara Private Hospital
state: Queensland
city: Townsville
country: Australia
facility: Townsville Hospital
state: Queensland
city: North Adelaide
country: Australia
facility: Adelaide Oncology and Haematology
state: South Australia
city: Ballarat Central
country: Australia
facility: Grampian Health (Ballarat Base Hospital)
state: Victoria
city: Traralgon
country: Australia
facility: Latrobe Regional Hospital
state: Victoria
city: Christchurch
country: New Zealand
facility: Christchurch Hospital
city: Dunedin
country: New Zealand
facility: Dunedin Hospital
city: Grafton
country: New Zealand
facility: Auckland City Hospital
city: Hamilton
country: New Zealand
facility: Waikato Hospital
city: Takapuna
country: New Zealand
facility: North Shore Hospital (Waitemata District Health Board)
Study officials:
affiliation: Calvary Mater Newcastle, Edith Street, Waratah, NSW 2298 Australia
name: Anoop Enjeti
role: PRINCIPAL_INVESTIGATOR
References: