RECRUITING

Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia

Conditions

Leukemia Myeloid Leukemia Monocytic Leukemia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

This is an open label, phase 1 study for AML subjects with relapsed or refractory disease or subjects in morphologic remission with MRD+ after first line therapy with venetoclax+HMA. A preliminary dose-finding cohort will be followed by 3 expansion cohorts.

Official Title

Mitoxantrone for Venetoclax Resistant Acute Myeloid Leukemia

Quick Facts

Study Start:2024-12

Study Completion:2027-11

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT06429449

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 80 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Subject must have confirmation of non-APL AML by WHO criteria and have been treated with first-line venetoclax/HMA (azacitidine or decitabine). 2. Subject must have relapsed disease per IWG criteria or disease refractory to first line venetoclax/HMA defined by less than a PR response after ≥ 1 complete cycle of venetoclax/HMA. 3. Subject must have either measurable residual disease (MRD+), as measured by FDA-approved flow cytometric test performed by Hematologics (cohort 3 and 4) or relapsed/refractory disease (cohort 1 and 2). 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 ≥ 60 mL/min, calculated using the formula CKD-EPI Creatinine Equation 7. Subject must have adequate heart function as measured by left ventricular ejection fraction (LVEF) \>50%, assessed by multigated acquisition (MUGA) or echocardiogram (ECHO) within 1 month prior to study day 1 8. Subject must have adequate liver function as demonstrated by: 1. aspartate aminotransferase (AST) ≤ 3.0 × ULN\* 2. alanine aminotransferase (ALT) ≤ 3.0 × ULN\* 3. bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome\* * Unless considered due to leukemic organ involvement 9. Non-sterile male subjects must use contraceptive methods with partner(s) at least prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. No contraception is required if male subjects are surgically sterile (vasectomy with medical assessment confirming surgical success) or if the male subject has a female partner who is postmenopausal or permanently sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy). 10. Female subjects must be either: 1. Postmenopausal; defined as Age \> 60 years with no menses for 12 or more months without an alternative medical cause; OR 2. Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); OR 3. If subject is of childbearing potential, use of contraception is required while on study treatment and for 6 months after the last dose. 11. Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed procedures.	1. Subject has known active CNS involvement from AML. 2. 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: 1. Significant active cardiac disease within the previous 6 months including: New York Heart Association heart failure \> class 2, unstable angina, or myocardial infarction. 2. Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia. 3. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. This includes history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease (e.g. 4. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Uncontrolled is defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment. 5. Subject has a history of other malignancies prior to study entry, with the exception of: 1. Adequately treated in situ carcinoma of the breast or cervix uteri 2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin 3. Prostate cancer not requiring therapy beyond hormonal therapy 4. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent 6. Subject has a white blood cell count \> 25 × 109/L. Note: hydroxyurea or apheresis are permitted to meet this criterion (cohort 3 only). 7. Pregnant or breast-feeding females. 8. Known or suspected hypersensitivity to azacitidine or mannitol. 9. Any prior exposure to an anthracycline or anthracenedione

Inclusion Criteria

Exclusion Criteria

1. Subject must have confirmation of non-APL AML by WHO criteria and have been treated with first-line venetoclax/HMA (azacitidine or decitabine).
2. Subject must have relapsed disease per IWG criteria or disease refractory to first line venetoclax/HMA defined by less than a PR response after ≥ 1 complete cycle of venetoclax/HMA.
3. Subject must have either measurable residual disease (MRD+), as measured by FDA-approved flow cytometric test performed by Hematologics (cohort 3 and 4) or relapsed/refractory disease (cohort 1 and 2).
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 ≥ 60 mL/min, calculated using the formula CKD-EPI Creatinine Equation
7. Subject must have adequate heart function as measured by left ventricular ejection fraction (LVEF) \>50%, assessed by multigated acquisition (MUGA) or echocardiogram (ECHO) within 1 month prior to study day 1
8. Subject must have adequate liver function as demonstrated by:
1. aspartate aminotransferase (AST) ≤ 3.0 × ULN\*
2. alanine aminotransferase (ALT) ≤ 3.0 × ULN\*
3. bilirubin ≤ 1.5 × ULN, unless due to Gilbert's syndrome\*
* Unless considered due to leukemic organ involvement
9. Non-sterile male subjects must use contraceptive methods with partner(s) at least prior to beginning study drug administration and continuing up to 90 days after the last dose of study drug. No contraception is required if male subjects are surgically sterile (vasectomy with medical assessment confirming surgical success) or if the male subject has a female partner who is postmenopausal or permanently sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy).
10. Female subjects must be either:
1. Postmenopausal; defined as Age \> 60 years with no menses for 12 or more months without an alternative medical cause; OR
2. Permanently surgically sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy); OR
3. If subject is of childbearing potential, use of contraception is required while on study treatment and for 6 months after the last dose.
11. Subject must voluntarily sign and date an informed consent, approved by an Institutional Review Board (IRB), prior to the initiation of any research directed procedures.

1. Subject has known active CNS involvement from AML.
2. 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:
1. Significant active cardiac disease within the previous 6 months including: New York Heart Association heart failure \> class 2, unstable angina, or myocardial infarction.
2. Renal, neurologic, psychiatric, endocrinologic, metabolic, immunologic, hepatic, cardiovascular disease, or bleeding disorder independent of leukemia.
3. Subject has a malabsorption syndrome or other condition that precludes enteral route of administration. This includes history of inflammatory bowel disease (e.g. Crohn's disease, ulcerative colitis), celiac disease (e.g.
4. Subject exhibits evidence of uncontrolled systemic infection requiring therapy (viral, bacterial or fungal). Uncontrolled is defined as ongoing signs/symptoms related the infection without improvement despite appropriate antibiotics, antiviral therapy and/or other treatment.
5. Subject has a history of other malignancies prior to study entry, with the exception of:
1. Adequately treated in situ carcinoma of the breast or cervix uteri
2. Basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin
3. Prostate cancer not requiring therapy beyond hormonal therapy
4. Previous malignancy confined and surgically resected (or treated with other modalities) with curative intent
6. Subject has a white blood cell count \> 25 × 109/L. Note: hydroxyurea or apheresis are permitted to meet this criterion (cohort 3 only).
7. Pregnant or breast-feeding females.
8. Known or suspected hypersensitivity to azacitidine or mannitol.
9. Any prior exposure to an anthracycline or anthracenedione

Contacts and Locations

Study Contact

Derek Schatz

CONTACT

720-848-0628

derek.schatz@cuanschutz.edu

Principal Investigator

Andrew Kent, MD, PhD

PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Study Locations (Sites)

University of Colorado Hospital

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

Andrew Kent, MD, PhD, PRINCIPAL_INVESTIGATOR, University of Colorado, Denver

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2024-12

Study Completion Date2027-11

Study Record Updates

Study Start Date2024-12

Study Completion Date2027-11

Terms related to this study

Additional Relevant MeSH Terms

Leukemia
Myeloid Leukemia
Monocytic Leukemia