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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04256317




Registration number
NCT04256317
Ethics application status
Date submitted
31/01/2020
Date registered
5/02/2020

Titles & IDs
Public title
A Study of ASTX030 (Cedazuridine in Combination With Azacitidine) in MDS, CMML, or AML
Scientific title
A Multi-phase, Dose-Escalation Followed by an Open-label, Randomized, Crossover Study of Oral ASTX030 (Cedazuridine and Azacitidine Given in Combination) Versus Subcutaneous Azacitidine in Subjects With Myelodysplastic Syndromes (MDS), Chronic Myelomonocytic Leukemia (CMML), or Acute Myeloid Leukemia (AML)
Secondary ID [1] 0 0
ASTX030-01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Myelodysplastic Syndromes 0 0
Chronic Myelocytic Leukemia 0 0
Acute Myeloid Leukemia 0 0
Myelodysplastic Syndrome/Neoplasm 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
Other 0 0 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Azacitidine
Treatment: Drugs - ASTX030 (cedazuridine + azacitidine)
Treatment: Drugs - Cedazuridine

Experimental: Phase 1, Stage A (Dose Escalation) - In Cycle 1 (28 days per cycle), single dose oral azacitidine will be administered, followed by subcutaneous (SC) azacitidine, ASTX030 and oral cedazuridine on a specific dosing schedule; in Cycle 2, oral ASTX030 (cedazuridine + azacitidine) will be administered

Experimental: Phase 1, Stage B (Dose Expansion) - Oral cedazuridine + azacitidine will be administered separately at the recommended dose for expansion (RDE)

Experimental: Phase 2, Sequence A - Oral ASTX030 (cedazuridine + azacitidine) will be administered in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles =3)

Experimental: Phase 2, Sequence B - SC azacitidine will be administered in Cycle 1, followed by oral cedazuridine + azacitidine tablets/capsules in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles =3)

Experimental: Phase 3, Sequence A - Participants will receive ASTX030 in Cycle 1, followed by SC azacitidine in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles =3)

Experimental: Phase 3, Sequence B - Participants will receive SC azacitidine in Cycle 1 followed by ASTX030 in Cycle 2; all participants will receive ASTX030 in subsequent cycles (Cycles =3)


Treatment: Drugs: Azacitidine
Tablets/Capsules for oral administration and powder for reconstitution to aqueous suspension for subcutaneous administration

Treatment: Drugs: ASTX030 (cedazuridine + azacitidine)
Tablets/Capsules for oral administration

Treatment: Drugs: Cedazuridine
Tablets for oral administration
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Total cycle area under the curve (AUC)0-24 exposures
Timepoint [1] 0 0
Up to 2 months
Secondary outcome [1] 0 0
Safety: Number of TEAEs
Timepoint [1] 0 0
Up to 36 months
Secondary outcome [2] 0 0
Change in DNA methylation
Timepoint [2] 0 0
Baseline in Phase 1 to the end of Cycle 2 in Phase 3 (28 days per cycle)
Secondary outcome [3] 0 0
Best clinical response rate for participants with MDS, CMML, or MDS/myeloproliferative neoplasms (MPN)
Timepoint [3] 0 0
Up to 36 months
Secondary outcome [4] 0 0
Best clinical response rate for participants with AML
Timepoint [4] 0 0
Up to 36 months
Secondary outcome [5] 0 0
AML-free survival for participants with MDS, CMML, or MDS/MPN
Timepoint [5] 0 0
Up to 36 months
Secondary outcome [6] 0 0
Duration of response
Timepoint [6] 0 0
Up to 36 months
Secondary outcome [7] 0 0
Overall survival
Timepoint [7] 0 0
Up to 36 months
Secondary outcome [8] 0 0
Time to response
Timepoint [8] 0 0
Up to 36 months
Secondary outcome [9] 0 0
Red blood cell (RBC) transfusion independence (TI)
Timepoint [9] 0 0
Up to 36 months
Secondary outcome [10] 0 0
Platelet transfusion independence (TI)
Timepoint [10] 0 0
Up to 36 months
Secondary outcome [11] 0 0
Pharmacokinetic parameter AUC
Timepoint [11] 0 0
Up to Day 8 in Cycle 2 (28 days per cycle)
Secondary outcome [12] 0 0
Pharmacokinetic parameter Cmax
Timepoint [12] 0 0
Up to Day 8 in Cycle 2 (28 days per cycle)
Secondary outcome [13] 0 0
Pharmacokinetic parameter Tmax
Timepoint [13] 0 0
Up to Day 8 in Cycle 2 (28 days per cycle)

Eligibility
Key inclusion criteria
1. Confirmed MDS, CMML, MDS/MPN, or AML who are candidates to receive and benefit from single agent azacitidine as follows and as applicable according to local country approvals and/or local institution standard practice:

1. French-American-British myelodysplastic syndrome subtypes: refractory anemia (RA) or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts (RAEB), refractory anemia with excess blasts in transformation (RAEB-T), or MDS with intermediate-2 or high risk MDS according to the International Prognostic Scoring System (IPSS). MDS/MPN patients including CMML according to the World Health Organization (WHO) 2016 classification are also eligible if they are candidates to receive single agent azacitidine per local institution standards; or
2. Previously untreated AML with 20% to 30% blasts present in bone marrow and multi-lineage dysplasia (Phase 2 and 3 only); or
3. Previously untreated AML with >30% blasts present in bone marrow, who are not eligible for stem cell transplant and unfit for intensive chemotherapy induction (Phase 2 and 3 only).
2. Participants with Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
3. Participants with adequate organ function defined as:

1. Hepatic: Total or direct bilirubin =2 × upper limit of normal (ULN); aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic pyruvic transaminase (SGPT) =2.5 × ULN.
2. Renal: Calculated creatinine clearance >50 mL/min/1.73 m^2 by Cockcroft-Gault formula or other medically acceptable formulas.
4. For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD) and must be =2 weeks off systemic immunosuppressive therapy before start of study treatment.
5. Participants with no major surgery within 2 weeks before first study treatment.
6. Participants with no cytotoxic chemotherapy within 4 weeks before first study treatment.
7. Able to swallow the number of tablets/capsules required for the treatment assignment within a 10-minute period and tolerate 4 hours of fasting.
8. Participants with projected life expectancy of at least 12 weeks.
9. Women of child-bearing potential (according to recommendations of the Clinical Trial Facilitation Group) must not be pregnant or breastfeeding and must have a negative pregnancy test at screening.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Active uncontrolled gastric or duodenal ulcer.
2. Poor medical risk because of other conditions such as uncontrolled systemic diseases or active uncontrolled bacterial, viral, or fungal infections.
3. Life-threatening illness (e.g., uncontrolled bleeding and patients at risk for or are experiencing leukostasis [AML]), uncontrolled medical condition or organ system dysfunction, or other reasons, which, in the investigator's opinion, could compromise the participant's safety, interfere with the absorption or metabolism of oral cedazuridine + azacitidine or compromise the integrity of the study outcomes.
4. Prior malignancy, except for adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, prostate cancer or breast cancer under control with hormone therapy, or other cancer from which the participant has been disease free for at least 2 years.
5. Participants with MDS/MPN who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
6. Previous treatment with more than 1 cycles of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
7. Treated with any investigational drug or therapy within 2 weeks, or 5 half lives, whichever is longer, before the protocol-defined first dose of study treatment, or ongoing clinically significant adverse events from previous treatment with investigational drug or therapy.
8. Known or suspected hypersensitivity to cedazuridine or azacitidine, or any of their excipients.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled 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
Crossover
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/05/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/04/2026
Actual
Sample size
Target
317
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Connecticut
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Massachusetts
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
North Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Ohio
Country [9] 0 0
United States of America
State/province [9] 0 0
Oregon
Country [10] 0 0
United States of America
State/province [10] 0 0
South Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
United States of America
State/province [13] 0 0
Washington
Country [14] 0 0
Canada
State/province [14] 0 0
Newfoundland and Labrador
Country [15] 0 0
Canada
State/province [15] 0 0
Ontario

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Taiho Oncology, Inc.
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Taiho Oncology, Inc.
Address 0 0
Country 0 0
Phone 0 0
+1 844-878-2446
Fax 0 0
Email 0 0
medicalinformation@taihooncology.com
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04256317