Venetoclax and Azacitidine for the Treatment of Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Chronic Myelomonocytic Leukemia

NCT04550442 | Active Not Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 2020-0128NCI-2020-06538
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial investigates the side effects and best dose of venetoclax when given together with azacitidine and to see how well it works in treating patients with high-risk myelodysplastic syndrome or chronic myelomonocytic leukemia that has come back (relapsed) or has not responded to treatment (refractory). Venetoclax may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. 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 and azacitidine together may help to control myelodysplastic syndrome or chronic myelomonocytic leukemia.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated dose (MTD) (Phase I)

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

  Up to 28 days

• Overall response rate (ORR) (Phase II)

  ORR is defined as the proportion of patients who had complete remission (CR), partial remission (PR) or marrow CR (mCR) lasting at least 4 weeks, or hematologic improvement (HI) lasting at least 8 weeks. Will estimate the overall response rate for the combination treatment, along with the 95% credible interval.

  Up to 5 years post-treatment

Secondary Outcomes (12)

• Rate of CR

  Up to 5 years post-treatment

• Rate of mCR

  Up to 5 years post-treatment

• Rate of hematologic improvement

  Up to 5 years post-treatment

• Rate of platelet transfusion independence

  Up to 5 years post-treatment

• Rate of red blood cell transfusion independence

  Up to 5 years post-treatment

Study Arms (1)

Treatment (venetoclax, azacitidine)

EXPERIMENTAL

Patients receive venetoclax PO daily on days 1-14 and azacitidine IV over 15 minutes or SC 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 IV or SC

Also known as: 5 AZC, 5-AC, 5-Azacytidine, 5-AZC, Azacytidine, Azacytidine, 5-, Ladakamycin, Mylosar, 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:

• Participants with post HMA-failure high-risk MDS (Int-2 or high risk by the IPSS with overall score \>/=1.5) with excess blasts \>5% with 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.
• Participants with relapsed/refractory chronic myelomonocytic leukemia (CMML) and therapy-related MDS are also eligible.
• Hydroxyurea is allowed to lower the white cell count \</= 10,000/µl prior to initiation of venetoclax.
• Adequate hepatic function including total bilirubin ≤ 2.0 x upper limit of normal (ULN) unless increase is due to Gilbert's disease or leukemic involvement, and ALT/AST ≤ 3.0 x ULN unless considered due to leukemic involvement.
• Adequate renal function as calculated using the modified Cockcroft-Gault equation of ≥ 30ml/min, OR creatinine \< 2x ULN, unless related to the disease.
• Signed written informed consent.
• 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.
• Age \>/= 18 years of age.
• ECOG/PS ≤2

You may not qualify if:

• Participants having received any prior BCL2 inhibitor therapy.
• Participants with MDS with IPSS risk categories Low or Int-1 (overall IPSS score \< 1.5).
• Participants with known HIV infection (due to potential drug-drug interactions between antiretroviral medications and venetoclax). HIV testing will be performed at screening, only if required per local guidelines or institutional standards.
• Participants known to be positive for hepatitis B or C infection \[HCV Ab indicative of a previous or current infection; and/or positive HBs Ag or detected sensitivity on HBV-DNA PCR test for HBc Ab and/or HBs Ab positivity\] with the exception of those with an undetectable viral load within 3 months of screening. (Hepatitis B or C testing is not required). Subjects with serologic evidence of prior vaccination to HBV \[i.e., HBs Ag-, and anti-HBs+\] may participate.
• Participants has received strong and/or moderate CYP3A inducers within 7 days prior to the initiation of study treatment.
• Participants has consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
• Participants has a cardiovascular disability status of New York Heart Association Class \> 2. Class 2 is defined as cardiac disease in which patients are comfortable at rest but ordinary physical activity results in fatigue, palpitations, dyspnea, or anginal pain.
• Participant has chronic respiratory disease that requires continuous oxygen, or significant history of renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, any other medical condition or known hypersensitivity to any of the study medications including excipients of azacitidine that in the opinion of the investigator would adversely affect his/her participating in this study.
• Participant has a malabsorption syndrome or other condition that precludes enteral route of administration.
• Participant exhibits evidence of other clinically significant uncontrolled systemic infection requiring therapy (viral, bacterial or fungal).
• Participant has received a live attenuated vaccine within 4 weeks prior to the first dose of study drug.
• Participant has a history of other malignancies within 2 years prior to study entry, with the exception of:
• Adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast;
• Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin;
• Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent; requires discussion with TA MD.

Sponsors & Collaborators

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

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• Related Info

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: September 9, 2020
• First Posted: September 16, 2020
• Study Start: September 4, 2020
• Primary Completion: March 31, 2026
• Study Completion: March 31, 2026
• Last Updated: January 12, 2026

Record last verified: 2026-01

Locations

US (1)