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Venetoclax and Azacitidine for the Treatment of High-Risk Recurrent or Refractory Myelodysplastic Syndrome | Clinical Trials | Clareo Health

TERMINATEDPHASE1/PHASE2

Venetoclax and Azacitidine for the Treatment of High-Risk Recurrent or Refractory Myelodysplastic Syndrome

Phase I/II of Venetoclax in Combination With Azacitidine in Treatment Naïve and Relapse Refractory High Risk MDS Individuals"

NCT04160052•M.D. Anderson Cancer Center

View on ClinicalTrials.gov

Summary

This phase I/II trial studies the side effects and best dose of venetoclax when given together with azacitidine in treating patients with high-risk myelodysplastic syndrome that has come back (recurrent) or does not respond to treatment (refractory). Drugs used in chemotherapy, such as venetoclax and 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.

Detailed Description

PRIMARY OBJECTIVE: I. To determine the safety and tolerability (phase 1) and overall response rate (ORR) (phase 2) of venetoclax in combination with azacitidine in patients with treatment-naive high-risk myelodysplastic syndrome (MDS) or chronic myelomonocytic leukemia (CMML) with bone marrow excess blasts \> 5% and patients that are relapsed/refractory to prior hypomethylating agent (HMA) therapy. SECONDARY OBJECTIVES: I. Rate of complete remission (CR). II. Rate of marrow/morphologic complete remission (mCR). III. Rate of hematologic improvement (HI; erythroid/platelet/neutrophil responses). IV. Rate of red blood cell (RBC) transfusion independence. V. Rate of platelet (PLT) transfusion independence. VI. Rate of cytogenetic response. VII. Rate of bone marrow blast response. VIII. Time to transformation to acute myeloid leukemia (AML). IX. Duration of response (DOR). X. Overall survival (OS). XI. Progression-free survival (PFS). XII. Time to next MDS treatment (TTNT). XIII. Event-free survival (EFS). EXPLORATORY OBJECTIVE: I. To investigate the effects of therapy on MDS and to identify biological markers of response to venetoclax and/or its combination with azacitidine. OUTLINE: This is a phase I, dose-escalation study of venetoclax followed by a phase II study. Patients receive venetoclax orally (PO) once daily (QD) on days 1-7 or 1-14 and azacitidine subcutaneously (SC) or intravenously (IV) over 15 minutes on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days and then every 3-6 months for up to 5 years.

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•For phase I, patients can be HMA-naive high-risk MDS (Int-2 or high risk by the International Prognostic Scoring System \[IPSS\] with overall score \>= 1.5) with excess blasts \> 5%, or relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with \> 5% blasts
•For phase II, patients will be divided into 2 cohorts: Cohort A: patients with HMA-naive high-risk MDS (Int-2 or high risk by the IPSS with overall score \>= 1.5) with excess blasts \> 5%. Cohort B: patients with relapsed/refractory MDS post-HMA failure (defined as prior receipt of 4 cycles of HMA therapy with failure to attain a response, or progression of disease or relapse at any time after prior response to HMA therapy) with \> 5% blasts are eligible. Note: Patients with chronic myelomonocytic leukemia (CMML) and therapy-related MDS are eligible. Hydroxyurea is allowed to lower the white cell count =\< 10,000/ul prior to initiation of venetoclax
•Total bilirubin \< 3 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement
•Alanine aminotransferase (ALT) \< 4 x ULN unless considered due to leukemic involvement
•Creatinine \< 2 x ULN unless related to the disease
•Signed written informed consent. Consent may be translated for Non-English Speaking Patients per institutional policy.
•Females must be surgically or biologically sterile or postmenopausal (amenorrheic for at least 12 months) or if of childbearing potential, must have a negative serum or urine pregnancy test within 72 hours before the start of the treatment. Women of childbearing potential must agree to use an adequate method of contraception during the study and until 3 months after the last treatment
•Males must be surgically or biologically sterile or agree to use an adequate method of contraception during the study until 3 months after the last treatment

Exclusion Criteria

•Patients having received any prior BCL2 inhibitor therapy
•Patients with MDS with IPSS risk categories low or Int-1 (overall IPSS score \< 1.5)
•Pregnant or breastfeeding
•Cognitively impaired patients

Locations (1)

M D Anderson Cancer Center

Houston, Texas, United States

Key Dates

Start Date

October 1, 2019

Primary Completion Date

February 3, 2026

Completion Date

February 3, 2026

Last Updated

February 12, 2026

Enrollment

ACTUAL participants

Conditions

Chronic Myelomonocytic LeukemiaMyelodysplastic SyndromeRecurrent Myelodysplastic SyndromeRefractory Myelodysplastic SyndromeTherapy-Related Myelodysplastic Syndrome

Interventions

Azacitidine

DRUG

Venetoclax

DRUG

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: February 12, 2026Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

View ClinicalTrials.gov Terms and Conditions

Venetoclax and Azacitidine for the Treatment of High-Risk Recurrent or Refractory Myelodysplastic Syndrome

Inclusion Criteria

Exclusion Criteria

Haplo-identical Transplantation for Severe Aplastic Anemia, Hypo-plastic MDS and PNH Using Peripheral Blood Stem Cells and Post-transplant Cyclophosphamide for GVHD Prophylaxis

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