Omacetaxine for Consolidation and Maintenance

Omacetaxine for Consolidation and Maintenance in Patients Age ≥ 55 With AML in First Remission: A Pilot Study

The purpose of this pilot study is to assess the safety and tolerability of omacetaxine for consolidation in patients age 55 and older with acute myelogenous leukemia (AML) in first complete remission following induction with cytarabine and an anthracycline, and also to assess the safety and tolerability of omacetaxine for maintenance in patients age 55 and older with acute AML in first complete remission following 3 consolidation courses with omacetaxine.

Study Overview

• Status: Terminated
• Conditions: Acute Myelogenous Leukemia (AML)
• Intervention / Treatment: Drug: Omacetaxine

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Emory University Winship Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of AML including de novo, secondary, or with an antecedent hematologic disorder (AHD) according to the World Health Organization (WHO) criteria.
2. Age ≥ 55 years.
3. Patient eligible for standard induction chemotherapy based on Eastern Cooperative Oncology Group (ECOG) performance status and vital organ function at the discretion of the treating physician.
4. Patients who received 1-2 cycles of hypomethylating therapy (decitabine azacitidine) are eligible.
5. Provide signed written informed consent.
6. Be able to comply with study procedures and follow-up examinations.
7. Be non-fertile or agree to use birth control during the study through the end of last treatment visit.

8. Adequate renal and hepatic function at the time of second registration:

   • Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN); and
   • Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 x ULN; and
   • Serum creatinine ≤ 1.2 x ULN.
9. ECOG performance ≤ 2 at the time of second registration.
10. Patients with a history of carcinoma in remission, on no therapy or on hormonal therapy for the adjuvant treatment of breast carcinoma or prostate carcinoma are included in the study.

Exclusion Criteria:

1. Diagnosis of acute promyelocytic leukemia (APL, French-American-British [FAB] classification M3 or WHO classification of APL with t (15;17)(q22;q12), (PML/retinoic acid receptor alpha [RARa] and variants).
2. Prior treatment with omacetaxine.
3. Relapsed or refractory AML.
4. Investigational agent received within 30 days prior to the first dose of study drug. If received any investigational agent prior to this time point, drug-related toxicities must have recovered to Grade 2 or less prior to first dose of study drug.
5. Psychiatric disorders that would interfere with consent, study participation, or follow-up.
6. Systemic fungal, bacterial, viral, or other infection not controlled (defined as exhibiting ongoing signs/symptoms related to the infection and without improvement, despite appropriate antibiotics or other treatment).
7. Any other severe concurrent disease, or have a history of serious organ dysfunction or disease involving the heart, kidney, liver, or other organ system that may place the patient at undue risk to undergo the proposed therapy. This includes uncontrolled hypertension and uncontrolled diabetes, as cases of life threatening hyperglycemia have been reported (using continuous infusion at higher doses of omacetaxine).
8. Active carcinoma requiring systemic chemotherapy or radiation therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Omacetaxine: Consolidation/Maintenance	Drug: Omacetaxine; Omacetaxine 1.25 mg/m² sub-cutaneously twice daily for 5 consecutive days every 28 (± 8) days for 3 cycles. Patients in continuous remission after 3 cycles of consolidation will receive maintenance omacetaxine 1.25 mg/m² twice daily for 3 days, every 28 days for up to 6 cycles; Other Names: Synribo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease Status Assessment Prior to Each Consolidation Cycle	Disease status will be assessed by a bone marrow aspirate and biopsy prior to each of 3 consolidation cycles (to ensure that patients are still in remission).	14 days
Assessment of Disease Status	Bone marrow biopsy and aspirate will be obtained.	1 month
Bone Marrow Aspirate to Confirm Continuous Remission	Bone marrow aspirate to confirm continuous remission will be obtained before starting maintenance and at 3 and 6 months from the start of maintenance.	3 months
Maintenance Toxicities	Toxicities will be monitored by history, physical examination, and laboratory monitoring during maintenance.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Consolidation Toxicities	Toxicities will be monitored by history, physical examination, and laboratory monitoring (CBC, serum chemistries to include renal and liver function tests) obtained weekly during consolidation and monthly during maintenance according to standard of care (Appendices C and D). Toxicity will be assessed according to the NCI Common Toxicity Criteria Version 4.0 (available at the NCI web site http://ctep.cancer.gov/reporting/ctc.html).	12 weeks

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: Teva Pharmaceuticals USA
• Investigators: Principal Investigator: Martha L. Arellano, MD, Emory University

Study record dates

Study Major Dates

• Study Start: May 1, 2013
• Primary Completion (ACTUAL): July 1, 2018
• Study Completion (ACTUAL): July 1, 2018

Study Registration Dates

• First Submitted: June 4, 2013
• First Submitted That Met QC Criteria: June 6, 2013
• First Posted (ESTIMATE): June 10, 2013

Study Record Updates

• Last Update Posted (ACTUAL): September 24, 2019
• Last Update Submitted That Met QC Criteria: September 5, 2019
• Last Verified: September 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Protein Synthesis Inhibitors; Homoharringtonine
• Other Study ID Numbers: IRB00057844; Winship2176-11 (OTHER: Other)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No