A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia

Myelodysplastic Syndromes Clinical Trial

— PREFER-HMA  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05883956
• Other study ID #: 393-419-00041
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 20, 2023
• Est. completion date: May 2025

Study information

• Verified date: June 2024
• Source: Otsuka Australia Pharmaceutical Pty Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 13
• Est. completion date: May 2025
• Est. primary completion date: January 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Leukemia, Myelomonocytic, Chronic
• Leukemia, Myelomonocytic, Juvenile
• Myelodysplastic Syndromes
• Patient Preference
• Preleukemia
• Syndrome

Intervention

Drug:
• Subcutaneous azacitidine
Subcutaneous azacitidine, 75mg/m2, 7 days
• Oral decitabine/cedazuridine
Oral decitabine 35mg/cedazuridine 100mg, once daily, 5 days

Locations

Country	Name	City	State
Australia	Grampian Health (Ballarat Base Hospital)	Ballarat Central	Victoria
Australia	Pindara Private Hospital	Benowa	Queensland
Australia	Calvary Mater Newcastle	Newcastle	New South Wales
Australia	Adelaide Oncology and Haematology	North Adelaide	South Australia
Australia	Townsville Hospital	Townsville	Queensland
Australia	Latrobe Regional Hospital	Traralgon	Victoria
New Zealand	Christchurch Hospital	Christchurch
New Zealand	Dunedin Hospital	Dunedin
New Zealand	Auckland City Hospital	Grafton
New Zealand	Waikato Hospital	Hamilton
New Zealand	North Shore Hospital (Waitemata District Health Board)	Takapuna

Sponsors (1)

Lead Sponsor	Collaborator
Otsuka Australia Pharmaceutical Pty Ltd

Countries where clinical trial is conducted

Australia,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the patient treatment preference in myelodysplasia questionnaire (pTPMQ)		Prior to initiation of Cycle 3 (each cycle is 28 days)
Primary	Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the pTPMQ		Prior to initiation of Cycle 5 (each cycle is 28 days)
Secondary	Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the carer treatment preference in myelodysplasia questionnaire (cTPMQ)		Prior to initiation of Cycle 3 (each cycle is 28 days)
Secondary	Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the cTPMQ		Prior to initiation of Cycle 5 (each cycle is 28 days)
Secondary	Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the medical treatment preference in myelodysplasia questionnaire (mTPMQ)		Prior to initiation of Cycle 4 (each cycle is 28 days)
Secondary	Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the mTPMQ		End of Study (EOS) Day 28
Secondary	Proportion of clinicians choosing oral decitabine/cedazuridine vs subcutaneous azacitidine for continuation of treatment and reasons for the treatment choice based on the mTPMQ		Cycle 5, Day 1 (each cycle is 28 days)
Secondary	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		Cycle 1, Day 1 (each cycle is 28 days)
Secondary	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		Cycle 1, Day 1 (each cycle is 28 days)
Secondary	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		Cycle 3, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 3, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 4, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 4, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 5, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 5, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 6, Day 5 (each cycle is 28 days)
Secondary	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		Cycle 6, Day 5 (each cycle is 28 days)
Secondary	The difference in the incidence of treatment discontinuation and reasons for treatment discontinuation		Baseline (pre-intervention) through to study completion (up to 6 cycles of treatment where each cycle is 28 days)
Secondary	Incidence and severity of adverse events upon study physician discretion.		Baseline (pre-intervention) through to study completion (up to 6 cycles of treatment where each cycle is 28 days)