ACTIVE_NOT_RECRUITING

Safety and Efficacy of Venetoclax With Escalating Doses of Omacetaxine in Patients With Acute Myeloid Leukemia Safety and Efficacy of Venetoclax With Escalating Doses of Omacetaxine in Patients With Acute Myeloid Leukemia (AML)

Conditions

Relapsed or Refractory Hematologic Malignancies

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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 will be a single arm, open label Phase Ib dose-escalation study of the combination of VEN and OM, conducted using an innovative Bayesian Optimal Interval-design, to find the MTD in participants with AML failing treatment with venetoclax-containing regimens. Treatment plan will consist of an induction phase, followed by a consolidation phase if applicable.

Official Title

VEN-OM: Phase IB/II Study Of Safety And Efficacy Of Venetoclax When Combined With Escalating Doses Of Omacetaxine In Patients With AML Failing Treatment With Venetoclax-Containing Regimens

Quick Facts

Study Start:2022-06-21

Study Completion:2025-07

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04926285

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 75 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. Age 18-75 years of age at time of consent. 2. Have relapsed/refractory AML (primary or secondary) and have progressed on ≥ 1 line of therapy, at least one of which must have included a VEN-containing regimen. 3. Eastern Cooperative Oncology Group (ECOG) Performance score 0-2 4. Prior cancer treatment must be completed at least 21 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline. 5. Life expectancy of 6 months or greater as determined by the treating physician. 6. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration. 7. Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB). 8. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. 9. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they have not experienced menstruation for at least 12 consecutive months 10. Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax. Females will be advised to use effective contraception for at least 6 months after the last dose of omacetaxine and males for at least 3 months after the last dose of omacetaxine. 11. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study. 6.2 Exclusion Criteria 1. Patients with history of prior use of Omacetaxine. 2. White blood cell count \> 25 × 109/L (hydroxyurea permitted to decrease WBC count). 3. History of other malignancies within 1 year prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. 4. Unresolved \> grade 2 DIC. 5. Investigational drug use within 4 weeks of study entry. 6. History of CHF requiring treatment, left ventricular ejection fraction ≤ 40%, cardiac insufficiency grade III or IV per New York Heart Association classification (NYHA; see Appendix 2), or chronic stable angina 7. Patients who are HIV positive. 8. Known CNS involvement with AML. 9. Previous hematopoietic stem cell transplant within 2 months. 10. Patients who are positive for hepatitis B or C infection with the exception of those with an undetectable viral load over the prior 3 months. Subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti-HBs+) may participate. 11. Active uncontrolled infection or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician. 12. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). 13. Patients who have received strong and/or moderate CYP3A inducers or inhibitors within 7 days prior to the initiation of study treatment unless therapy is deemed necessary by the treating physician. (See Section 8.7.2, Table 3 and Appendix 3). 14. Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment. 15. Malabsorption syndrome or other condition that precludes enteral route of administration. 16. Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up. 17. Unable or unwilling to undergo a screening bone marrow study. 18. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study. 1. Age 18-75 years of age at time of consent. 2. Have relapsed/refractory AML (primary or secondary) and have progressed on ≥ 1 line of therapy, at least one of which must have included a VEN-containing regimen. 3. Eastern Cooperative Oncology Group (ECOG) Performance score 0-2 (see Appendix 1). 4. Prior cancer treatment must be completed at least 21 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline. 5. Life expectancy of 6 months or greater as determined by the treating physician. 6. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration. 7. Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB). 8. NOTE: HIPAA authorization may be included in the informed consent or obtained separately. 9. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they have not experienced menstruation for at least 12 consecutive months 10. Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax. Females will be advised to use effective contraception for at least 6 months after the last dose of omacetaxine and males for at least 3 months after the last dose of omacetaxine. 11. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.	1. Patients with history of prior use of Omacetaxine. 2. White blood cell count \> 25 × 109/L (hydroxyurea permitted to decrease WBC count). 3. History of other malignancies within 1 year prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. 4. Unresolved \> grade 2 DIC. 5. Investigational drug use within 4 weeks of study entry. 6. History of CHF requiring treatment, left ventricular ejection fraction ≤ 40%, cardiac insufficiency grade III or IV per New York Heart Association classification (NYHA; see Appendix 2), or chronic stable angina 7. Patients who are HIV positive. 8. Known CNS involvement with AML. 9. Previous hematopoietic stem cell transplant within 2 months. 10. Patients who are positive for hepatitis B or C infection with the exception of those with an undetectable viral load over the prior 3 months. Subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti-HBs+) may participate. 11. Active uncontrolled infection or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician. 12. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). 13. Patients who have received strong and/or moderate CYP3A inducers or inhibitors within 7 days prior to the initiation of study treatment unless therapy is deemed necessary by the treating physician. (See Section 8.7.2, Table 3 and Appendix 3). 14. Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment. 15. Malabsorption syndrome or other condition that precludes enteral route of administration. 16. Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up. 17. Unable or unwilling to undergo a screening bone marrow study. 18. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.

Inclusion Criteria

Exclusion Criteria

1. Age 18-75 years of age at time of consent.
2. Have relapsed/refractory AML (primary or secondary) and have progressed on ≥ 1 line of therapy, at least one of which must have included a VEN-containing regimen.
3. Eastern Cooperative Oncology Group (ECOG) Performance score 0-2
4. Prior cancer treatment must be completed at least 21 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.
5. Life expectancy of 6 months or greater as determined by the treating physician.
6. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration.
7. Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB).
8. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
9. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they have not experienced menstruation for at least 12 consecutive months
10. Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax. Females will be advised to use effective contraception for at least 6 months after the last dose of omacetaxine and males for at least 3 months after the last dose of omacetaxine.
11. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.
6.2 Exclusion Criteria
1. Patients with history of prior use of Omacetaxine.
2. White blood cell count \> 25 × 109/L (hydroxyurea permitted to decrease WBC count).
3. History of other malignancies within 1 year prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
4. Unresolved \> grade 2 DIC.
5. Investigational drug use within 4 weeks of study entry.
6. History of CHF requiring treatment, left ventricular ejection fraction ≤ 40%, cardiac insufficiency grade III or IV per New York Heart Association classification (NYHA; see Appendix 2), or chronic stable angina
7. Patients who are HIV positive.
8. Known CNS involvement with AML.
9. Previous hematopoietic stem cell transplant within 2 months.
10. Patients who are positive for hepatitis B or C infection with the exception of those with an undetectable viral load over the prior 3 months. Subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti-HBs+) may participate.
11. Active uncontrolled infection or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician.
12. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
13. Patients who have received strong and/or moderate CYP3A inducers or inhibitors within 7 days prior to the initiation of study treatment unless therapy is deemed necessary by the treating physician. (See Section 8.7.2, Table 3 and Appendix 3).
14. Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
15. Malabsorption syndrome or other condition that precludes enteral route of administration.
16. Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up.
17. Unable or unwilling to undergo a screening bone marrow study.
18. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.
1. Age 18-75 years of age at time of consent. 2. Have relapsed/refractory AML (primary or secondary) and have progressed on ≥ 1 line of therapy, at least one of which must have included a VEN-containing regimen.
3. Eastern Cooperative Oncology Group (ECOG) Performance score 0-2 (see Appendix 1).
4. Prior cancer treatment must be completed at least 21 days prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to ≤ Grade 1 or baseline.
5. Life expectancy of 6 months or greater as determined by the treating physician.
6. Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration.
7. Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB).
8. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
9. Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration. NOTE: Females are considered of child bearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they have not experienced menstruation for at least 12 consecutive months 10. Females of childbearing potential and males must be willing to use effective contraception during treatment and for at least 30 days after the last dose of Venetoclax. Females will be advised to use effective contraception for at least 6 months after the last dose of omacetaxine and males for at least 3 months after the last dose of omacetaxine.
11. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study.

1. Patients with history of prior use of Omacetaxine.
2. White blood cell count \> 25 × 109/L (hydroxyurea permitted to decrease WBC count).
3. History of other malignancies within 1 year prior to study entry, with the exception of: adequately treated in situ carcinoma of the cervix uteri or carcinoma in situ of breast; basal cell carcinoma of the skin or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent.
4. Unresolved \> grade 2 DIC.
5. Investigational drug use within 4 weeks of study entry.
6. History of CHF requiring treatment, left ventricular ejection fraction ≤ 40%, cardiac insufficiency grade III or IV per New York Heart Association classification (NYHA; see Appendix 2), or chronic stable angina
7. Patients who are HIV positive.
8. Known CNS involvement with AML.
9. Previous hematopoietic stem cell transplant within 2 months.
10. Patients who are positive for hepatitis B or C infection with the exception of those with an undetectable viral load over the prior 3 months. Subjects with serologic evidence of prior vaccination to HBV (i.e., HBs Ag-, and anti-HBs+) may participate.
11. Active uncontrolled infection or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician.
12. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
13. Patients who have received strong and/or moderate CYP3A inducers or inhibitors within 7 days prior to the initiation of study treatment unless therapy is deemed necessary by the treating physician. (See Section 8.7.2, Table 3 and Appendix 3).
14. Patients who have consumed grapefruit, grapefruit products, Seville oranges (including marmalade containing Seville oranges) or Starfruit within 3 days prior to the initiation of study treatment.
15. Malabsorption syndrome or other condition that precludes enteral route of administration.
16. Psychological, familial, sociological, or geographical condition that would preclude study compliance and follow-up.
17. Unable or unwilling to undergo a screening bone marrow study.
18. Other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for enrollment in this study.

Contacts and Locations

Principal Investigator

John Quigley, MD

PRINCIPAL_INVESTIGATOR

University of Illinois at Chicago

Study Locations (Sites)

University of Illinois Cancer Center

Chicago, Illinois, 60612

United States

Collaborators and Investigators

Sponsor: University of Illinois at Chicago

John Quigley, MD, PRINCIPAL_INVESTIGATOR, University of Illinois at Chicago

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 Date2022-06-21

Study Completion Date2025-07

Study Record Updates

Study Start Date2022-06-21

Study Completion Date2025-07

Terms related to this study

Additional Relevant MeSH Terms

Relapsed or Refractory Hematologic Malignancies