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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)

Primary Purpose

Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic

Status
Not yet recruiting
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Subcutaneous azacitidine
Oral decitabine/cedazuridine
Sponsored by
Otsuka Australia Pharmaceutical Pty Ltd
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Myelodysplastic Syndromes

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).

Sites / Locations

  • Calvary Mater Newcastle
  • Pindara Private Hospital
  • Townsville Hospital
  • Adelaide Oncology and Haematology
  • Grampian Health (Ballarat Base Hospital)
  • Latrobe Regional Hospital
  • Christchurch Hospital
  • Dunedin Hospital
  • Auckland City Hospital
  • Waikato Hospital
  • North Shore Hospital (Waitemata District Health Board)

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

ABBA

BAAB

Arm Description

Cycle 1: Oral decitabine/cedazuridine; Cycle 2: Subcutaneous azacitidine; Cycle 3: Subcutaneous azacitidine; Cycle 4: Oral decitabine/cedazuridine

Cycle 1: Subcutaneous azacitidine; Cycle 2: Oral decitabine/cedazuridine; Cycle 3: Oral decitabine/cedazuridine; Cycle 4: Subcutaneous azacitidine

Outcomes

Primary Outcome Measures

Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the patient treatment preference in myelodysplasia questionnaire (pTPMQ)
Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the pTPMQ

Secondary Outcome Measures

Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the carer treatment preference in myelodysplasia questionnaire (cTPMQ)
Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the cTPMQ
Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the medical treatment preference in myelodysplasia questionnaire (mTPMQ)
Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the mTPMQ
Proportion of clinicians choosing oral decitabine/cedazuridine vs subcutaneous azacitidine for continuation of treatment and reasons for the treatment choice based on the mTPMQ
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
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
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
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
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
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
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
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
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
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
The difference in the incidence of treatment discontinuation and reasons for treatment discontinuation
Incidence and severity of adverse events upon study physician discretion.

Full Information

First Posted
April 25, 2023
Last Updated
September 11, 2023
Sponsor
Otsuka Australia Pharmaceutical Pty Ltd
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1. Study Identification

Unique Protocol Identification Number
NCT05883956
Brief Title
A Study Comparing Treatment Preference Between Oral Decitabine/Cedazuridine and Azacitidine in Myelodysplastic Syndrome, Low-Blast Acute Myeloid Leukemia, or Chronic Myelomonocytic Leukemia
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 2023 (Anticipated)
Primary Completion Date
April 2025 (Anticipated)
Study Completion Date
May 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Otsuka Australia Pharmaceutical Pty Ltd

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelodysplastic Syndromes, Leukemia, Myeloid, Acute, Leukemia, Myelomonocytic, Chronic, Patient Preference

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
42 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
ABBA
Arm Type
Active Comparator
Arm Description
Cycle 1: Oral decitabine/cedazuridine; Cycle 2: Subcutaneous azacitidine; Cycle 3: Subcutaneous azacitidine; Cycle 4: Oral decitabine/cedazuridine
Arm Title
BAAB
Arm Type
Active Comparator
Arm Description
Cycle 1: Subcutaneous azacitidine; Cycle 2: Oral decitabine/cedazuridine; Cycle 3: Oral decitabine/cedazuridine; Cycle 4: Subcutaneous azacitidine
Intervention Type
Drug
Intervention Name(s)
Subcutaneous azacitidine
Intervention Description
Subcutaneous azacitidine, 75mg/m2, 7 days
Intervention Type
Drug
Intervention Name(s)
Oral decitabine/cedazuridine
Intervention Description
Oral decitabine 35mg/cedazuridine 100mg, once daily, 5 days
Primary Outcome Measure Information:
Title
Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the patient treatment preference in myelodysplasia questionnaire (pTPMQ)
Time Frame
Prior to initiation of Cycle 3 (each cycle is 28 days)
Title
Proportion of patients reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the pTPMQ
Time Frame
Prior to initiation of Cycle 5 (each cycle is 28 days)
Secondary Outcome Measure Information:
Title
Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the carer treatment preference in myelodysplasia questionnaire (cTPMQ)
Time Frame
Prior to initiation of Cycle 3 (each cycle is 28 days)
Title
Proportion of carers reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the cTPMQ
Time Frame
Prior to initiation of Cycle 5 (each cycle is 28 days)
Title
Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the medical treatment preference in myelodysplasia questionnaire (mTPMQ)
Time Frame
Prior to initiation of Cycle 4 (each cycle is 28 days)
Title
Proportion of clinicians reporting preference for oral decitabine/cedazuridine vs subcutaneous azacitidine on the mTPMQ
Time Frame
End of Study (EOS) Day 28
Title
Proportion of clinicians choosing oral decitabine/cedazuridine vs subcutaneous azacitidine for continuation of treatment and reasons for the treatment choice based on the mTPMQ
Time Frame
Cycle 5, Day 1 (each cycle is 28 days)
Title
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
Time Frame
Cycle 1, Day 1 (each cycle is 28 days)
Title
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
Time Frame
Cycle 1, Day 1 (each cycle is 28 days)
Title
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
Time Frame
Cycle 3, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 3, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 4, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 4, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 5, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 5, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 6, Day 5 (each cycle is 28 days)
Title
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
Time Frame
Cycle 6, Day 5 (each cycle is 28 days)
Title
The difference in the incidence of treatment discontinuation and reasons for treatment discontinuation
Time Frame
Baseline (pre-intervention) through to study completion (up to 6 cycles of treatment where each cycle is 28 days)
Title
Incidence and severity of adverse events upon study physician discretion.
Time Frame
Baseline (pre-intervention) through to study completion (up to 6 cycles of treatment where each cycle is 28 days)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Michelle Ta
Phone
+61 (0) 2 8021 9825
Email
Michelle.Ta@au.otsuka.com
First Name & Middle Initial & Last Name or Official Title & Degree
Taliesha Paine
Phone
+61 (0) 2 8021 9825
Email
Taliesha.Paine@au.otsuka.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Anoop Enjeti
Organizational Affiliation
Calvary Mater Newcastle, Edith Street, Waratah, NSW 2298 Australia
Official's Role
Principal Investigator
Facility Information:
Facility Name
Calvary Mater Newcastle
City
Newcastle
State/Province
New South Wales
Country
Australia
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nick Stankovich
Facility Name
Pindara Private Hospital
City
Benowa
State/Province
Queensland
Country
Australia
Facility Name
Townsville Hospital
City
Townsville
State/Province
Queensland
Country
Australia
Facility Name
Adelaide Oncology and Haematology
City
North Adelaide
State/Province
South Australia
Country
Australia
Facility Name
Grampian Health (Ballarat Base Hospital)
City
Ballarat Central
State/Province
Victoria
Country
Australia
Facility Name
Latrobe Regional Hospital
City
Traralgon
State/Province
Victoria
Country
Australia
Facility Name
Christchurch Hospital
City
Christchurch
Country
New Zealand
Facility Name
Dunedin Hospital
City
Dunedin
Country
New Zealand
Facility Name
Auckland City Hospital
City
Grafton
Country
New Zealand
Facility Name
Waikato Hospital
City
Hamilton
Country
New Zealand
Facility Name
North Shore Hospital (Waitemata District Health Board)
City
Takapuna
Country
New Zealand

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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