RECRUITING

A Multi-phase Study of ASTX030 (Azacitidine and Cedazuridine) in Myeloid Neoplasm Alone or in Combination With Venetoclax in AML (AZTOUND Study)

Conditions

Myelodysplastic Syndromes Acute Myeloid Leukemia Myelodysplastic Syndrome/Neoplasm Chronic Myelomonocytic Leukemia ASTX030 Myeloid Neoplasm Hematologic Disease Leukemia Acute Myeloid Leukemia (AML)Myelodysplastic Syndrome (MDS)Chronic Myelomonocytic Leukemia (CMML)Vidaza™Azacitidine Azacitidine and cedazuridine drug combination Venetoclax Venclexta™

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Study ASTX030-01 is a multi-phase study comprising of Phases 1-3 Monotherapy arms and a Phase 1 Combination Therapy arm Phase 1 Monotherapy consists of an open-label Dose Escalation Stage (Stage A) using multiple cohorts at escalating dose levels of oral cedazuridine and azacitidine (only one study drug will be escalated at a time) followed by a Dose Expansion Stage (Stage B). Phase 2 Monotherapy is a randomized, open-label, crossover study to compare oral ASTX030 to subcutaneous (SC) azacitidine. Phase 3 Monotherapy is a randomized open-label crossover study comparing the final fixed dose of oral ASTX030 to SC azacitidine. Phase 1 Combination Therapy is an open-label, multicenter, randomized, exploratory study comparing ASTX030 and SC azacitidine in combination with venetoclax in participants with AML. The duration of this multi-phase study is approximately 7 years.

Official Title

A Multi-phase, Pharmacokinetics, Safety, and Efficacy Study of ASTX030 (Azacitidine and Cedazuridine) as Monotherapy in Subjects With Myeloid Neoplasm or in Combination With Venetoclax in Subjects With AML (AZTOUND Study)

Quick Facts

Study Start:2020-05-21

Study Completion:2028-05-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04256317

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Phase 2 Monotherapy: 1. Has Confirmed MDS, CMML, or other MDS/MPN diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice. * Phase 3 Monotherapy: 1. Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice: 2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. 3. Participants with adequate organ function. 4. For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD). 5. Participants with no major surgery within 3 weeks before first study treatment. 6. Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment. 7. Is 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. * Phase 1 Combination Therapy: 1. Has histological confirmation of newly diagnosed AML by World Health Organization (WHO) 2022 criteria. 2. Participants with projected life expectancy of at least 12 weeks. 3. Must be considered ineligible for intensive induction chemotherapy defined by the following: 4. Has an ECOG Performance Status of 0-2 for participants ≥75 years of age or 0-3 for participants 18 to 74 years of age.	* All Monotherapy Phases: 1. Has an active uncontrolled gastric or duodenal ulcer. 2. Has poor medical risk because of other conditions. 3. Has known human immunodeficiency virus (HIV) infection. 4. Is known to be positive for Hepatitis B or C infection. 5. Has a life-threatening illness. 6. Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required. 7. Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly. 8. Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only). 9. Has been 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. 10. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients. 11. Cannot discontinue treatment with any drugs that delay gastric emptying such as glucagon-like peptide-1 (GLP-1) and/or gastric inhibitory polypeptide (GIP) agonists in Cycles 1 and 2 of the study. 12. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients. * Phase 1 Combination Therapy: 1. Has a history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation. 2. Has the following karyotype abnormalities: t(15;17) or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy. 3. Has known active central nervous system involvement from AML. 4. Has known human immunodeficiency virus (HIV) infection. 5. Is known to be positive for Hepatitis B or C infection. 6. Has severe hepatic impairment 7. Has severe renal impairment 8. Has a malabsorption syndrome or other condition that precludes enteral route of administration. 9. Has a cardiovascular disability status of New York Heart Association Class \>2. 10. Has significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease; or any other medical condition that in the opinion of the investigator would adversely affect his/her participation in this study. 11. Has clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal). 12. Has a history of other malignancies prior to study entry with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or adequately treated and controlled with other modalities); and any early stage malignancy for which no definitive therapy is required. 13. Has a WBC count \>25,000/ microliters (μL) (hydroxyurea treatment is permitted to meet this criterion). 14. Has received treatment with any of the following: 1. A hypomethylating agent (azacitidine or decitabine) or venetoclax, including prior treatment for MDS. 2. Chimeric Antigen Receptor (CAR)-T cell therapy. 3. Investigational therapies for MDS or AML. 15. Cannot discontinue treatment with any of the following: 1. Prophylactic antifungal therapy with CYP3A inhibitor activity or other concomitant medications with moderate or strong CYP3A inhibitor activity ≥7 days or 5 halflives, whichever is greater, prior to Cycle 1 Day 1 (C1D1). 2. Drugs that are strong CYP3A or P-gp inhibitors ≥7 days or 5 half-lives, whichever is greater, prior to C1D1. 16. Cannot avoid concomitant drugs known as moderate or strong CYP3A inducers. 17. Cannot discontinue treatment with any drugs that delay gastric emptying such as GLP-1 and/or GIP agonists in Cycles 1 and 2 of the study. 18. Is participating in another research study requiring interventions such as drug therapy or study procedures. 19. Has a known or suspected hypersensitivity to cedazuridine, azacitidine, venetoclax, or any of their excipients. 20. Has known significant mental illness or other conditions such as alcohol or other substance abuse or addictions 21. Consumes grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit ≤7 days prior to C1D1.

Inclusion Criteria

Exclusion Criteria

* Phase 2 Monotherapy:
1. Has Confirmed MDS, CMML, or other MDS/MPN diagnosis who are candidates to receive and benefit from single agent azacitidine and as applicable according to local country approvals and/or local institution standard practice.
* Phase 3 Monotherapy:
1. Has confirmed MDS or CMML and is a candidate to receive and benefit from single agent azacitidine as applicable according to local country approvals and/or local institution standard practice:
2. Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1.
3. Participants with adequate organ function.
4. For participants with prior allogeneic stem cell transplant, no evidence of graft-versus-host disease (GVHD).
5. Participants with no major surgery within 3 weeks before first study treatment.
6. Participants with no cytotoxic chemotherapy (excluding hydroxyurea) within 4 weeks before first study treatment.
7. Is 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.
* Phase 1 Combination Therapy:
1. Has histological confirmation of newly diagnosed AML by World Health Organization (WHO) 2022 criteria.
2. Participants with projected life expectancy of at least 12 weeks.
3. Must be considered ineligible for intensive induction chemotherapy defined by the following:
4. Has an ECOG Performance Status of 0-2 for participants ≥75 years of age or 0-3 for participants 18 to 74 years of age.

* All Monotherapy Phases:
1. Has an active uncontrolled gastric or duodenal ulcer.
2. Has poor medical risk because of other conditions.
3. Has known human immunodeficiency virus (HIV) infection.
4. Is known to be positive for Hepatitis B or C infection.
5. Has a life-threatening illness.
6. Has a history of other malignancies prior to study entry, with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected or adequately treated and controlled with other modalities; and any early stage malignancy for which no definitive therapy is required.
7. Participants with MDS/MPN including CMML who have clinical extramedullary disease including clinically palpable hepatomegaly or splenomegaly.
8. Has previous treatment with more than 1 cycle of decitabine, azacitidine, or guadecitabine (Phases 2 and 3 only).
9. Has been 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.
10. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
11. Cannot discontinue treatment with any drugs that delay gastric emptying such as glucagon-like peptide-1 (GLP-1) and/or gastric inhibitory polypeptide (GIP) agonists in Cycles 1 and 2 of the study.
12. Has a known or suspected hypersensitivity to cedazuridine or azacitidine or any of their excipients.
* Phase 1 Combination Therapy:
1. Has a history of MPN including myelofibrosis, essential thrombocythemia, polycythemia vera, chronic myeloid leukemia with or without BCR-ABL1 translocation, or AML with BCR-ABL1 translocation.
2. Has the following karyotype abnormalities: t(15;17) or other acute promyelocytic leukemia variants that remain sensitive to all-trans retinoic acid (ATRA) therapy.
3. Has known active central nervous system involvement from AML.
4. Has known human immunodeficiency virus (HIV) infection.
5. Is known to be positive for Hepatitis B or C infection.
6. Has severe hepatic impairment
7. Has severe renal impairment
8. Has a malabsorption syndrome or other condition that precludes enteral route of administration.
9. Has a cardiovascular disability status of New York Heart Association Class \>2.
10. Has significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular, or pulmonary disease; or any other medical condition that in the opinion of the investigator would adversely affect his/her participation in this study.
11. Has clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial, or fungal).
12. Has a history of other malignancies prior to study entry with the exception of adequately treated in situ carcinoma of the breast or cervix uteri; localized basal cell carcinoma or squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or adequately treated and controlled with other modalities); and any early stage malignancy for which no definitive therapy is required.
13. Has a WBC count \>25,000/ microliters (μL) (hydroxyurea treatment is permitted to meet this criterion).
14. Has received treatment with any of the following:
1. A hypomethylating agent (azacitidine or decitabine) or venetoclax, including prior treatment for MDS.
2. Chimeric Antigen Receptor (CAR)-T cell therapy.
3. Investigational therapies for MDS or AML.
15. Cannot discontinue treatment with any of the following:
1. Prophylactic antifungal therapy with CYP3A inhibitor activity or other concomitant medications with moderate or strong CYP3A inhibitor activity ≥7 days or 5 halflives, whichever is greater, prior to Cycle 1 Day 1 (C1D1).
2. Drugs that are strong CYP3A or P-gp inhibitors ≥7 days or 5 half-lives, whichever is greater, prior to C1D1.
16. Cannot avoid concomitant drugs known as moderate or strong CYP3A inducers.
17. Cannot discontinue treatment with any drugs that delay gastric emptying such as GLP-1 and/or GIP agonists in Cycles 1 and 2 of the study.
18. Is participating in another research study requiring interventions such as drug therapy or study procedures.
19. Has a known or suspected hypersensitivity to cedazuridine, azacitidine, venetoclax, or any of their excipients.
20. Has known significant mental illness or other conditions such as alcohol or other substance abuse or addictions
21. Consumes grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or starfruit ≤7 days prior to C1D1.

Contacts and Locations

Study Contact

Taiho Oncology, Inc.

CONTACT

+1 844-878-2446

medicalinformation@taihooncology.com

Study Locations (Sites)

Keck School of Medicine of USC

Los Angeles, California, 90089

United States

UCI Health - Chao Family Comprehensive Cancer Center

Orange, California, 92868

United States

Yale University

New Haven, Connecticut, 06510

United States

University of Miami - Sylvester Comprehensive Cancer Center

Miami, Florida, 33136

United States

University of Emory - Winship Cancer Institute

Atlanta, Georgia, 30322

United States

Dana-Farber Cancer Institute

Boston, Massachusetts, 02114

United States

John Theurer Cancer Center / Hackensack University

Hackensack, New Jersey, 07601

United States

Roswell Park Comprehensive Cancer Center

Buffalo, New York, 14263

United States

New York University Langone Hospital - Long Island

Mineola, New York, 11501

United States

Perlmutter Cancer Center - 34th Street

New York, New York, 10016

United States

Icahn School of Medicine at Mount Sinai

New York, New York, 10029

United States

Weill Cornell Medical Center

New York, New York, 10065

United States

James P. Wilmot Cancer Center

Rochester, New York, 14642

United States

Duke University

Durham, North Carolina, 27705

United States

Ohio State University Comprehensive Cancer Center (OSUCCC) - The James Cancer Hospital and Solove Research Institute

Columbus, Ohio, 43210

United States

Oregon Health and Science University

Portland, Oregon, 97239

United States

Oregon Oncology Specialists

Salem, Oregon, 97301

United States

Hollings Cancer Center

Charleston, South Carolina, 29425

United States

Vanderbilt University Medical Center

Nashville, Tennessee, 37232

United States

Baylor Research Institute dba Baylor Scott & White Research Institute

Dallas, Texas, 75204

United States

University of Texas Southwestern Medical Center

Dallas, Texas, 75390

United States

MD Anderson Cancer Center

Houston, Texas, 77030

United States

Seattle Cancer Care Alliance

Seattle, Washington, 98109

United States

Froedtert & Medical College of Wisconsin

Milwaukee, Wisconsin, 53226

United States

Collaborators and Investigators

Sponsor: Taiho Oncology, Inc.

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-05-21

Study Completion Date2028-05-01

Study Record Updates

Study Start Date2020-05-21

Study Completion Date2028-05-01

Terms related to this study

Keywords Provided by Researchers

ASTX030
Myeloid Neoplasm
Hematologic Disease
Leukemia
Acute Myeloid Leukemia (AML)
Myelodysplastic Syndrome (MDS)
Chronic Myelomonocytic Leukemia (CMML)
Vidaza™
Azacitidine
Azacitidine and cedazuridine drug combination
Venetoclax
Venclexta™

Additional Relevant MeSH Terms

Myelodysplastic Syndromes
Acute Myeloid Leukemia
Myelodysplastic Syndrome/Neoplasm
Chronic Myelomonocytic Leukemia