Combining venetoclax and azacitidine to treat high-risk myelodysplastic syndrome
Phase I/II of Venetoclax in Combination With Azacitidine in Treatment Naïve and Relapse Refractory High Risk MDS Individuals"
This study is testing if combining two medications, venetoclax and azacitidine, can help people with high-risk myelodysplastic syndrome who haven't responded well to other treatments.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 116 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | M.D. Anderson Cancer Center Academic / other |
| Drugs / interventions | chemotherapy |
| Locations | 1 site (Houston, Texas) |
| Trial ID | NCT04160052 on ClinicalTrials.gov |
What this trial studies
This clinical trial evaluates the safety and effectiveness of venetoclax in combination with azacitidine for patients with high-risk myelodysplastic syndrome (MDS) that is either recurrent or refractory to previous treatments. The study is divided into two phases: the first phase focuses on determining the optimal dosage and safety profile, while the second phase assesses the overall response rate and other secondary outcomes such as complete remission rates and overall survival. Patients will receive venetoclax orally and azacitidine either subcutaneously or intravenously over a series of treatment cycles. The trial also aims to identify biological markers that may predict response to the treatment.
Who should consider this trial
Good fit: Ideal candidates include patients with high-risk MDS or chronic myelomonocytic leukemia who are either treatment-naive or have not responded to prior hypomethylating agent therapy.
Not a fit: Patients with low-risk MDS or those who have not received prior treatment may not benefit from this study.
Why it matters
Potential benefit: If successful, this treatment could provide a new effective option for patients with high-risk myelodysplastic syndrome who have limited treatment alternatives.
How similar studies have performed: Other studies have shown promising results with similar combinations of venetoclax and azacitidine, indicating potential for success in this approach.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Houston, Texas
- M D Anderson Cancer Center — Houston, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Guillermo Garcia-Manero — M.D. Anderson Cancer Center
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.