Description:
This study aims to treat non-elderly adult patients, who were previously untreated for acute
myeloid leukemia, using venetoclax and azacitidine.
Title
- Brief Title: Venetoclax and Azacitidine for Non-Elderly Adult Patients With Acute Myeloid Leukemia
- Official Title: Safety and Efficacy of Venetoclax and Azacitidine for Newly Diagnosed Non-Elderly Adult Patients (Aged 18-59) With Acute Myeloid Leukemia
Clinical Trial IDs
- ORG STUDY ID:
18-0709.cc
- NCT ID:
NCT03573024
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Azacitidine | | Azacitidine and Venetoclax |
Venetoclax | | Azacitidine and Venetoclax |
Purpose
This study aims to treat non-elderly adult patients, who were previously untreated for acute
myeloid leukemia, using venetoclax and azacitidine.
Detailed Description
This is a phase II study that seeks to treat patients ages 18-59 who have acute myeloid
leukemia but have never been treated before. It will use venetoclax and azacitidine, and
patients can receive up to four cycles of this medication. Depending on the level of
recovery, patients will either be forced to come off study or have the option to continue the
medication, receive maintenance therapy, or pursue an allogeneic stem cell transplant.
Trial Arms
Name | Type | Description | Interventions |
---|
Azacitidine and Venetoclax | Experimental | Azacitidine will be given intravenously for 7 days. Venetoclax will be given orally. The patient will start out with 100mg and progress to 600mg. Once 600mg is reached, the patient will stay at this dose until the 28 day cycle is finished. | |
Eligibility Criteria
Inclusion Criteria:
A subject will be eligible for study participation if he/she meets the following criteria
within 28 days prior to the first day of therapy (bone marrow biopsy can be performed 28
days prior to the first day of therapy). Historical records are permitted per Investigator
discretion.
1. Subject must have confirmation of non-APL and AML by WHO criteria45
2. Subject must have received no prior treatment for AML
3. Age ≥18 years, ≤59 years
4. Without clinical signs of active central nervous system disease
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 who are pre-menopausal and have not had a hysterectomy or oophorectomy
must agree to use two reliable forms of contraception simultaneously or to practice
complete abstinence from heterosexual intercourse during the following time periods
related to this study: 1) for at least 28 days before starting therapy; 2) throughout
the entire duration of treatment; 3) during dose interruptions; and 4) for at least 90
days after discontinuation of therapy (last dose of study drug).
10. Subject must voluntarily sign and date an informed consent, approved by an
Institutional Review Board (IRB), prior to the initiation of any research directed
screening procedures.
11. Subject must have adverse risk disease as defined by the European LeukemiaNet46
(Appendix B) 5.3.2 Exclusion Criteria
A subject will not be eligible for study participation if he/she meets any of the following
criteria:
1. Subject has received disease modifying treatment for myelodysplastic syndrome (MDS) or
AML. ATRA given for clinical suspicion of APL will not be exclusionary and no washout
will be required in this scenario.
2. Subject is known to be positive for HIV. HIV testing is not required.
3. 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
4. Subject has received within 7 days prior to the first dose of study drug:steroid
therapy for anti-neoplastic intent; strong and moderate CYP3A inhibitors; strong and
moderate CYP3A inducers.
5. Subject is informed that consumption of the following fruits is prohibited 3 days
prior to the initiation of study treatment and throughout participation: grapefruit,
grapefruit products, Seville oranges (including marmalade containing Seville oranges)
or Star fruit.
6. 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
7. Subject has a malabsorption syndrome or other condition that precludes enteral route
of administration
8. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral,
bacterial or fungal)
9. 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.
10. Subject has a white blood cell count >25 × 10^9/L or absolute blast count of >50
10^9/L. Hydroxyurea and leukapheresis are permitted, if clinically indicated.
11. Patients willing to receive intensive induction chemotherapy
12. Pregnant and breastfeeding females.
Maximum Eligible Age: | 59 Years |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Response Rate, measured by the European Leukemia Net definition: (CRMRD-+CR+CRi+MLFS) |
Time Frame: | Study start date to study end date, or death, whichever comes first, up to 4 years |
Safety Issue: | |
Description: | The (CRMRD-+CR+CRi+MLFS) shows non-inferiority of venetoclax with azacitidine when compared with historical controls who received induction chemotherapy. |
Secondary Outcome Measures
Measure: | Incidence of Minimal Residual Disease (MRD) Negative Responses |
Time Frame: | Study start date to study end date, or death, whichever comes first, up to 4 years |
Safety Issue: | |
Description: | Number of new cases of Complete Remission, Complete Remission with Incomplete Blood Count Recovery, or Morphologic Leukemia Free State. This will be measure by multi-dimensional flow cytometry with a sensitivity to 0.1%. |
Measure: | Remission Duration |
Time Frame: | Study start date to study end date, or death, whichever comes first, up to 4 years |
Safety Issue: | |
Description: | Remission Duration will be defined as the length of time a patient does not display leukemic blasts or extramedullary disease |
Measure: | One Year Event Free Survival |
Time Frame: | Study start date to study end date, or death, whichever comes first, up to 4 years |
Safety Issue: | |
Description: | Determined using Kaplan Meier survival analysis methods with 95% confidence intervals. |
Measure: | Overall Survival |
Time Frame: | Study start date to study end date, or death, whichever comes first, up to 4 years |
Safety Issue: | |
Description: | Overall Survival will be defined as the time from administration of the initial doses until death from any cause. Determined using Kaplan Meier survival analysis methods with 95% confidence intervals. |
Measure: | Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] |
Time Frame: | Study start date to study end date, or death, whichever comes first, up to 4 years |
Safety Issue: | |
Description: | Safety and tolerability analysis of azacitidine and venetoclax will be summarized by dose and severity as assessed by the Common Toxicity Criteria for Adverse Events (CTCAE) version 4.0 and relationship to study drug. |
Details
Phase: | Phase 2 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | University of Colorado, Denver |
Trial Keywords
- Venetoclax
- Azacitidine
- Non-Elderly
- Previously Untreated
Last Updated
February 21, 2021