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

NCT04160052 | Terminated Phase 1 FDA Drug

• 2 other identifiers: 2019-0368NCI-2019-06873
• Study Type: interventional
• Target: 51
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome; Recurrent Myelodysplastic Syndrome; Refractory Myelodysplastic Syndrome; Therapy-Related Myelodysplastic Syndrome

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) of the combination regimen of venetoclax and azacitidine (Phase I)

  The MTD is the highest dose level in which \< 2 patients of 6 develop first cycle dose-limiting toxicity.

  Up to 8 weeks

• Incidence of adverse events (Phase I)

  Safety data will be summarized by category, severity, and frequency.

  Up to 5 years

Secondary Outcomes (14)

• Overall response rate (Phase 2)

  Up to 5 years

• Rate of CR

  Up to 5 years

• Rate of marrow/morphologic CR

  Up to 5 years

• Rate of hematologic improvement

  Up to 5 years

• Rate of red blood cell transfusion independence

  Up to 5 years

Other Outcomes (2)

• Effects of therapy on myelodysplastic syndrome

  Up to 5 years

• Biological markers of response

  Up to 5 years

Study Arms (1)

Treatment (venetoclax, azacitidine)

EXPERIMENTAL

Patients receive venetoclax orally PO QD on days 1-7 or 1-14 and azacitidine SC or IV over 15 minutes on days 1-5. Cycles repeat every 4-8 weeks in the absence of disease progression or unacceptable toxicity.

Drug: Azacitidine; Drug: Venetoclax

Interventions

Azacitidine DRUG

Given SC or IV

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

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:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (1)

• Bazinet A, Darbaniyan F, Jabbour E, Montalban-Bravo G, Ohanian M, Chien K, Kadia T, Takahashi K, Masarova L, Short N, Alvarado Y, Yilmaz M, Ravandi F, Andreeff M, Kanagal-Shamanna R, Ganan-Gomez I, Colla S, Qiao W, Huang X, McCue D, Mirabella B, Kantarjian H, Garcia-Manero G. Azacitidine plus venetoclax in patients with high-risk myelodysplastic syndromes or chronic myelomonocytic leukaemia: phase 1 results of a single-centre, dose-escalation, dose-expansion, phase 1-2 study. Lancet Haematol. 2022 Oct;9(10):e756-e765. doi: 10.1016/S2352-3026(22)00216-2. Epub 2022 Sep 2.

  PMID: 36063832 DERIVED

Related Links

• MD Anderson Cancer Center

MeSH Terms

Conditions

Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes

Interventions

Azacitidine; venetoclax

Condition Hierarchy (Ancestors)

Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

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

• Guillermo Garcia-Manero

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2019
• First Posted: November 12, 2019
• Study Start: October 1, 2019
• Primary Completion: February 3, 2026
• Study Completion: February 3, 2026
• Last Updated: February 12, 2026

Record last verified: 2026-01

Locations

US (1)