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

• Status: Recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: M.D. Anderson Cancer Center
• Collaborator: National Cancer Institute (NCI)
• Treatments: Azacitidine; Venetoclax

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

• 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