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)

NCT04926285 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2021-0450
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Relapsed or Refractory Hematologic Malignancies

Outcome Measures

Primary Outcomes (1)

• To establish the maximum tolerated dose (MTD) of Omacetaxine in combination with Venetoclax

  Subjects will be monitored for dose limiting toxicities until Day 42 before escalation to the next dose may occur

  42 Days

Secondary Outcomes (6)

• To measure the the efficacy of the combination of Omacetaxine with Venetoclax in achieving overall response rate (ORR) after 3 cycles

  3 Cycles (12 weeks)

• To evaluate adverse events of patients taking Omacetaxine in combination with Venetoclax

  12 months

• To evaluate the overall survival (OS)

  6 months

• To evaluate the overall survival (OS)

  12 months

• To evaluate the event free survival (EFS)

  6 months

Other Outcomes (7)

• To measure and evaluate urinary concentration of TIMP-2 x IGFBP7 in urine samples

  3 Cycles (12 weeks)

• To measure and evaluate KIM-137 concentration in urine samples

  3 Cycles (12 weeks)

• To quantify the rate of protein synthesis on patient bone marrow

  3 Cycles (12 weeks)

Study Arms (4)

Cohort 1

EXPERIMENTAL

Omacetaxine 0.625 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Drug: Omacetaxine; Drug: Venetoclax

Cohort 2

EXPERIMENTAL

Omacetaxine 1.25 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Drug: Omacetaxine; Drug: Venetoclax

Cohort 3

EXPERIMENTAL

Omacetaxine 2.0 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Drug: Omacetaxine; Drug: Venetoclax

Cohort 4

EXPERIMENTAL

Omacetaxine 2.5 mg/m2 SQ injection q12h days 1-7 with Venetoclax 400 mg orally daily on days 4-28 Cycles are 28 days

Drug: Omacetaxine; Drug: Venetoclax

Interventions

Omacetaxine DRUG

Escalating doses of Omacetaxine 0.625 mg/m2 q12h, 1.25 mg/m2 q12h, 2.0 mg/m2 q12h, and 2.5 mg/m2 q12h

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Venetoclax DRUG

Venetoclax at 400mg

Cohort 1; Cohort 2; Cohort 3; Cohort 4

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years of age at time of consent.
• 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.
• Eastern Cooperative Oncology Group (ECOG) Performance score 0-2
• 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.
• i. With the exception of Hydroxyurea; if Hydroxyurea is used to reduce the white blood blast count to \< 25 x 109/L, then it must be discontinued at least 48 hours prior to registration and bone marrow/peripheral blood sampling, and the subject must have recovered from all reversible acute toxic effects to ≤ Grade 1 or baseline.
• Life expectancy of 6 months or greater as determined by the treating physician.
• Demonstrate adequate organ function as defined in the table below; all screening labs to be obtained within 28 days prior to registration.
• System Laboratory Value Renal Creatinine/Calculated creatinine clearance (CrCl) CrCl ≥ 50 mL/min using the Cockcroft-Gault formula Hepatic Bilirubin ≤ 1.5 × upper limit of normal (ULN). Excluding patients diagnosed with Gilbert's syndrome Aspartate aminotransferase (AST) ≤ 3 × ULN Alanine aminotransferase (ALT) ≤ 3 × ULN
• Provided written informed consent and HIPAA authorization for release of personal health information, approved by an Institutional Review Board (IRB).
• NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• 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
• 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.
• 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.

You may not qualify if:

• Subjects meeting any of the criteria below may not participate in the study:
• Patients with history of prior use of Omacetaxine.
• White blood cell count \> 25 × 109/L (hydroxyurea permitted to decrease WBC count).
• 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.
• Unresolved \> grade 2 DIC.
• Investigational drug use within 4 weeks of study entry.
• 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
• Patients who are HIV positive.
• Known CNS involvement with AML.
• Previous hematopoietic stem cell transplant within 2 months.
• 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.
• Active uncontrolled infection or severe systemic infection. Enrollment is possible after control of infection, at discretion of the treating physician.
• Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
• 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).
• 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.

Sponsors & Collaborators

• University of Illinois at Chicago: lead

Study Sites (1)

University of Illinois Cancer Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Recurrence; Hematologic Neoplasms

Interventions

Homoharringtonine; venetoclax

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Neoplasms by Site; Neoplasms; Hematologic Diseases; Hemic and Lymphatic Diseases

Intervention Hierarchy (Ancestors)

Harringtonines; Alkaloids; Heterocyclic Compounds; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 4 or More Rings

Study Officials

• John Quigley, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: June 8, 2021
• First Posted: June 15, 2021
• Study Start: June 21, 2022
• Primary Completion: January 29, 2024
• Study Completion: February 6, 2025
• Last Updated: March 16, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)