Venetoclax and Azacitidine for Treatment of Therapy Related or Secondary Myelodysplastic Syndrome

NCT05379166 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: OSU-20420NCI-2021-08484
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 3

Brief Summary

This phase II trial studies the effect of venetoclax and azacitidine in treating patients with therapy related or secondary myelodysplastic syndrome. Venetoclax may stop the growth of cancer cells by blocking Bcl-2, a protein needed for cancer cell survival. Chemotherapy drugs, such as azacitidine, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving venetoclax in combination with azacitidine may work better in treating patients with therapy related or secondary myelodysplastic syndrome.

Conditions

Therapy-Related Myelodysplastic Syndrome; Secondary Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (1)

• Complete remission (CR)

  Defined by 2023 International Working Group (IWG) criteria. A point estimate and 95% exact (i.e., Clopper-Pearson) confidence interval will be computed for the CR rate within the efficacy-evaluable population.

  At the end of Cycle 4 (each cycle is 28 days) or earlier based on bone marrow results

Secondary Outcomes (13)

• Treatment emergent adverse events (AEs)

  Up to 30 days after last dose of study drug

• Overall response rate (ORR)

  At the end of the last cycle of study drug (each cycle is 28 days)

• Cytogenetic response rate (CCyR)

  At the end of the last cycle of study drug (each cycle is 28 days)

• Overall survival (OS)

  From date of death or the last known alive date for participants who withdraw from or complete the study without dying, assessed up to 24 months

• Duration of response (DOR)

  From earliest occurrence of PR, mCR, or CR to onset of progressive disease, assessed up to 24 months

Other Outcomes (3)

• Detection of cytogenetic abnormalities

  Up to 12 months or last bone marrow exam

• Biometric measures recorded by the FitBit (e.g., heart rate, number of steps taken, activity time, calories burned)

  At the end of cycle 1 of study drug (each cycle is 28 days)

• Patient-reported outcomes (PROs)

  Up to 12 months or end of treatment clinical visit

Study Arms (1)

Treatment (venetoclax, azacitidine)

EXPERIMENTAL

Patients receive venetoclax PO QD on days 1-14 and azacitidine IV over 10-40 minutes on days 1-7 or days 1-5 of week 1 and days 1 and 2 of week 2. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Other: Quality-of-Life Assessment; Other: Questionnaire Administration; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given IV

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, Onureg, U-18496, Vidaza

Treatment (venetoclax, azacitidine)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (venetoclax, azacitidine)

Questionnaire Administration OTHER

Ancillary studies

Treatment (venetoclax, azacitidine)

Venetoclax DRUG

Given PO

Also known as: ABT-0199, ABT-199, ABT199, GDC-0199, RG7601, Venclexta, Venclyxto

Treatment (venetoclax, azacitidine)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to understand and the willingness to sign a written informed consent document
• Age \>= 18 years at time of informed consent. Both men and women and members of all races and ethnic groups will be included
• Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• Previously untreated therapy related myelodysplastic syndrome (t-MDS) with Revised International Prognostic Scoring System (IPSS-R) risk categories Intermediate, High or Very High (i.e., minimum IPSS-R score of 3.5) and presence of \< 20% bone marrow blasts per bone marrow biopsy/aspirate
• Patients with t-MDS which is defined as patients who have had prior anti-cancer therapy including chemotherapy and/or radiation therapy
• Aspartate aminotransferase (AST) \< 3.0 x upper limit of normal (ULN) x upper limit of normal (ULN; local laboratory)
• Alanine aminotransferase (ALT) \< 3.0 x ULN x ULN
• Total bilirubin =\< 2 x ULN (except for patients with known Gilbert's syndrome)
• Creatinine clearance \>= 30 mL/min OR serum creatinine \< 1.5 x the ULN
• White blood cell (WBC) count =\< 10,000/uL
• Females of childbearing potential (FOCBP) must agree to adequate contraception (1 form of contraception or abstinence) from the screening visit until 30 days following the last dose of venetoclax. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• FOCBP are those who have not been surgically sterilized or have not been free from menses for \> 1 year without an alternative medical cause
• Male patients of childbearing potential having intercourse with females of childbearing potential must agree to abstain from heterosexual intercourse or have their partner use 2 forms of contraception from the screening visit until 90 days after the last dose of study treatment. They must also refrain from sperm donation from the screening visit until 90 days following the last dose of study treatment

You may not qualify if:

• Participant has received prior therapy with a venetoclax or other BH3 mimetic. Note: Prior supportive care in form of transfusions or growth factors, etc., is not considered prior therapy. Supportive care should be discontinued \>= 14 days prior to the first dose of study drug. Subjects may continue oral corticosteroids for management of conditions other than MDS (e.g., asthma, rheumatoid arthritis) at a stable daily dose equivalent to =\< 10 mg prednisone during screening and study participation
• Subject has a diagnosis other than previously untreated de novo MDS with IPSS-R risk categories Intermediate, High or Very High, including:
• MDS with IPSS-R risk categories Very Low or Low (overall IPSS score \< 3)
• MDS evolving from a pre-existing myeloproliferative neoplasm (MPN)
• MDS/MPN including chronic myelomonocytic leukemia (CMML), atypical chronic myeloid leukemia (CML), juvenile myelomonocytic leukemia (JMML) and unclassifiable MDS/MPN
• Patients who are suitable for and willing to receive intensive chemotherapy or eligible to proceed to allogeneic stem cell transplantation without additional therapy
• Known history of testing positive for Human Immunodeficiency Virus (HIV) infections, Hepatitis B, or Hepatitis C. For countries where HIV status is mandatory: testing positive for HIV during screening using a local test.
• Clinically significant ventricular arrhythmia (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de pointes)
• Uncontrolled intercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, serious cardiac arrhythmia, myocardial infarction within 6 months prior to enrollment, New York Heart Association (NYHA) class III or IV heart failure
• Patients with uncontrolled infection will not be enrolled until infection is treated and under control
• Hypersensitivity to any study agent when administered alone. Any concurrent condition that, in the Investigator's opinion, would jeopardize the safety of the patient or compliance with the protocol
• Any psychiatric illness that prevents patient from informed consent process
• Pregnant of breastfeeding at the time of enrollment
• Subject has received allogeneic HSCT or solid organ transplantation
• Subject has a concurrent active malignancy requiring treatment or with an expected life expectancy less than 1 year with the exception of below. Any subject with a concurrent active malignancy will be reviewed by the PI for eligibility prior to enrollment

Sponsors & Collaborators

• Uma Borate: lead

Study Sites (3)

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Related Links

• The Jamesline

MeSH Terms

Interventions

Azacitidine; venetoclax

Intervention Hierarchy (Ancestors)

Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Study Officials

• Uma M Borate, MD

  Ohio State University Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: March 15, 2022
• First Posted: May 18, 2022
• Study Start: June 23, 2022
• Primary Completion: January 27, 2026
• Study Completion: April 15, 2026
• Last Updated: March 13, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)