Overview

Azacitidine and Venetoclax as Induction Therapy With Venetoclax Maintenance in the Elderly With AML

Status:
Active, not recruiting
Trial end date:
2023-10-01
Target enrollment:
0
Participant gender:
All
Summary
This study is being done to determine if treatment with azacitidine and venetoclax is effective treatment for elderly patients with acute myeloid leukemia (AML) who have not received previous treatment. Azacitidine and venetoclax will be given as induction treatment followed by venetoclax maintenance treatment for patients who respond to the induction treatment.
Phase:
Phase 2
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
University of Colorado, Denver
Treatments:
Azacitidine
Venetoclax
Criteria
Inclusion Criteria:

1. Subject must have confirmation of non-APL AML by WHO criteria and be ineligible or
unwilling to undergo treatment with a standard cytarabine and anthracycline induction
regimen due to co-morbidities or other factors

2. Subject must have received no prior treatment for AML; hydroxyurea is not considered a
treatment and is allowed

3. Subject must be ≥ 60 years of age

4. Subject must have a projected life expectancy of at least 12 weeks

5. Subject must have an Eastern Cooperative Oncology Group (ECOG) Performance status of
≤2

6. Subject must have adequate renal function as demonstrated by a calculated creatinine
clearance ≥ 30 mL/min; determined via urine collection for 24-hour creatinine
clearance or by the Cockcroft Gault formula

7. Subject must have adequate liver function as demonstrated by:

- aspartate aminotransferase (AST) ≤ 3.0 × ULN*

- alanine aminotransferase (ALT) ≤ 3.0 × ULN*

- bilirubin ≤ 3.0 × ULN, unless due to Gilbert's syndrome*

- Unless considered due to leukemic organ involvement

8. Non-sterile male subjects must use contraceptive methods with partner(s) prior to
beginning study drug administration and continuing up to 90 days after the last dose
of study drug. Male subjects must agree to refrain from sperm donation from initial
study drug administration until 90 days after the last dose of study drug.

9. Female subjects must be either:

- Postmenopausal; defined as Age > 55 years with no menses for 12 or more months
without an alternative medical cause; OR

- Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy
or hysterectomy)

10. Subject must voluntarily sign and date an informed consent, approved by an
Institutional Review Board (IRB), prior to the initiation of any screening or
study-specific procedures.

Exclusion Criteria:

1. Subject has received treatment with a hypomethylating agent and/or other
chemotherapeutic agent either conventional or experimental for myelodysplastic
syndrome (MDS) or AML

2. Subject has acute promyelocytic leukemia

3. Subject has known active CNS involvement from AML

4. Subject is known to be positive for HIV. HIV testing is not required

5. Subject is known to be positive for hepatitis B or C infection with the exception of
those with an undetectable viral load. Hepatitis B or C testing is not required and
subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag, anti-HBs+
and anti-HBc-) may participate

6. Subject has received anticancer therapies including chemotherapy, radiotherapy or
other investigational therapy, including targeted small molecule agents within 5
half-lives prior to first dose of study drug

7. Subject has received biologic agents (e.g. monoclonal antibodies) for anti-neoplastic
intent within 30 days prior to first dose of study drug

8. Subject has received the following within 7 days prior to the first dose of the study
drug:

- Steroid therapy for anti-neoplastic intent;

- Strong and Moderate CYP3A inhibitors (see Appendix A for examples)

- Strong and Moderate CYP3A inducers (see Appendix A for examples)

9. Subject has consumed grapefruit, grapefruit products, Seville oranges (including
marmalade containing Seville oranges) or Star fruit within 3 days prior to the
initiation of study treatment

10. Subject has any history of clinically significant condition(s) that in the opinion of
the investigator would adversely affect his/her participating in this study including,
but not limited to:

- New York Heart Association heart failure > class 2

- Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic,
cardiovascular disease, or bleeding disorder independent of leukemia

11. Subject has a malabsorption syndrome or other condition that precludes enteral route
of administration

12. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral,
bacterial or fungal)

13. Subject has a history of other malignancies prior to study entry, with the exception
of:

- Adequately treated in situ carcinoma of the breast or cervix uteri

- Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin

- Prostate cancer with no plans for therapy of any kind

- Previous malignancy confined and surgically resected (or treated with other
modalities) with curative intent

14. Subject has a white blood cell count > 25 × 109/L. Note: hydroxyurea is permitted to
meet this criteria

15. Any subject who is a candidate for intensive induction therapy and agrees to receive
this therapy