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

Launched by M.D. ANDERSON CANCER CENTER · Nov 8, 2019

Keywords

ClinConnect Summary

This clinical trial is studying the combination of two medications, venetoclax and azacitidine, to treat patients with high-risk myelodysplastic syndrome (MDS) that is either recurring or not responding to previous treatments. MDS is a condition where the bone marrow does not produce enough healthy blood cells, leading to various health issues. The goal of the trial is to determine the best dose of these medications and to monitor any side effects they may cause. By working in different ways, these drugs aim to stop the growth of abnormal blood cells.

To be eligible for the trial, participants generally need to be between 65 and 74 years old and have either never received certain treatments for MDS before or have not responded to them after receiving multiple cycles. The trial is currently recruiting participants of any gender. If you join, you can expect regular check-ups to monitor your health and how you respond to the treatment. It's also important to note that women who can become pregnant must use effective birth control during the study, and those who are pregnant or breastfeeding cannot participate.

Gender

ALL

Eligibility 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