Clinical Trials /

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

NCT03466294

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Azacitidine and Venetoclax as Induction Therapy With Venetoclax Maintenance in the Elderly With AML
  • Official Title: Azacitidine and Venetoclax (ABT-199) as Induction Therapy With Venetoclax Maintenance in Previously Untreated Elderly Patients With Acute Myeloid Leukemia (AML)

Clinical Trial IDs

  • ORG STUDY ID: 17-7821.cc
  • NCT ID: NCT03466294

Conditions

  • Acute Myeloid Leukemia

Interventions

DrugSynonymsArms
Azacitidine and VenetoclaxAzacitidine and Venetoclax

Purpose

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.

Detailed Description

      This is a phase 2 study for elderly patients who have not received previous treatment for
      acute myeloid leukemia (AML). Up to 42 patients will be enrolled. All patients will be
      treated with azacitidine and venetoclax until a minimal residual disease (MRD) negative
      response is achieved. Once patients achieve a MRD negative composite response, azacitidine
      will be discontinued and venetoclax dose will be decreased to "maintenance" dose.
    

Trial Arms

NameTypeDescriptionInterventions
Azacitidine and VenetoclaxExperimentalOn day 1 of cycle 1, Azacitidine 75 mg/m2 will be given by injection or infusion, and will continue for 7 days. Azacitidine doses will be given in subsequent cycles for patients who do not achieve response. Venetoclax will be administered orally once daily on days 2 through 28 in cycle 1. Beginning with cycle 2, and each subsequent cycle, venetoclax will be administered Days 1 through 28.
  • Azacitidine and Venetoclax

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:60 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Duration of response to azacitidine and venetoclax treatment
Time Frame:From the first day a response is documented to the first day of disease progression
Safety Issue:
Description:Determine how long responses last in patients treated with azacitidine and venetoclax followed by venetoclax maintenance treatment

Secondary Outcome Measures

Measure:Frequency of Minimal Residual Disease (MRD) negative composite responses within the "induction phase" of azacitidine and venetoclax
Time Frame:From Day 28, the first day a response is documented to end of cycle bone marrow biopsies, through 5 years
Safety Issue:
Description:The number of patients who achieve an MRD negative composite response
Measure:The time needed to achieve an MRD negative composite response
Time Frame:From first dose of treatment to first day response is documented by bone marrow biopsy
Safety Issue:
Description:The median number of days that have elapsed leading to an MRD negative composite response
Measure:The one-year overall survival (OS) of older, newly diagnosed AML patients treated with "induction phase" of azacitidine with venetoclax followed by a maintenance Phase of venetoclax alone.
Time Frame:From date of study enrollment to one year after enrollment
Safety Issue:
Description:The number of patients who survive to one year after date of study enrollment
Measure:Hematologic Toxicity as defined by the 2017 ELN AML Recommendations
Time Frame:From the day venetoclax with azacitidine is administered to the end of maintenance venetoclax alone, up to one year
Safety Issue:
Description:Hematologic toxicities will be measured by incidence of febrile neutropenia, ≥ grade 2 bleeding complications and number of transfusions received

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:University of Colorado, Denver

Trial Keywords

  • Azacitidine
  • Venetoclax
  • AML

Last Updated