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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Myelodysplastic Syndromes; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Chronic; Patient Preference
• Intervention / Treatment: Drug: Subcutaneous azacitidine; Drug: Oral decitabine/cedazuridine

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Taliesha Paine; Phone Number: +61 (0) 2 8021 9825; Email: Taliesha.Paine@au.otsuka.com
• Study Contact Backup: Name: Francesco Castaldi; Phone Number: +61 (0) 2 8021 9825; Email: Francesco.Castaldi@au.otsuka.com

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ABBA; Cycle 1: Oral decitabine/cedazuridine; Cycle 2: Subcutaneous azacitidine; Cycle 3: Subcutaneous azacitidine; Cycle 4: Oral decitabine/cedazuridine	Drug: Subcutaneous azacitidine; Subcutaneous azacitidine, 75mg/m2, 7 days; Drug: Oral decitabine/cedazuridine; Oral decitabine 35mg/cedazuridine 100mg, once daily, 5 days
Active Comparator: BAAB; Cycle 1: Subcutaneous azacitidine; Cycle 2: Oral decitabine/cedazuridine; Cycle 3: Oral decitabine/cedazuridine; Cycle 4: Subcutaneous azacitidine	Drug: Subcutaneous azacitidine; Subcutaneous azacitidine, 75mg/m2, 7 days; Drug: Oral decitabine/cedazuridine; Oral decitabine 35mg/cedazuridine 100mg, once daily, 5 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)
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 Outcome Measures

Outcome Measure	Time Frame
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)
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)
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)
Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the mTPMQ	End of Study (EOS) Day 28
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)
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)

Collaborators and Investigators

• Sponsor: Otsuka Australia Pharmaceutical Pty Ltd
• Investigators: Principal Investigator: Anoop Enjeti, Calvary Mater Newcastle, Edith Street, Waratah, NSW 2298 Australia

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2023
• Primary Completion (Estimated): April 1, 2025
• Study Completion (Estimated): May 1, 2025

Study Registration Dates

• First Submitted: April 25, 2023
• First Submitted That Met QC Criteria: May 29, 2023
• First Posted (Actual): June 1, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 12, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Disease Attributes; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Syndrome; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Preleukemia; Leukemia, Myelomonocytic, Chronic; Leukemia, Myelomonocytic, Juvenile; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Decitabine; Azacitidine
• Other Study ID Numbers: 393-419-00041

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No