A Clinical Trial of Omacetaxine, Azacitidine, and Growth-Colony Stimulating Factor (G-CSF) for Myelodysplastic Syndromes (MDS)

A Phase I/II Clinical Trial of Omacetaxine, Azacitidine, and G-CSF for Relapsed and/or Refractory Myelodysplastic Syndromes

The purpose of this study is to determine the safety and establish the maximum tolerated dose (MTD) of omacetaxine in combination with azacitidine and G-CSF in patients with relapsed and/or refractory MDS.

Study Overview

• Status: Withdrawn
• Conditions: Myelodysplastic Syndromes
• Intervention / Treatment: Drug: Omacetaxine; Drug: Azacitidine; Drug: G-CSF

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida Health Shands Cancer Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age >= 18 years;
• Informed consent;
• Low- and intermediate-risk MDS that has failed to achieve any hematologic improvement after at least 4 cycles of induction therapy or has relapsed after any duration of any hematologic response. Prior therapy with azanucleosides (i.e., azacitidine, decitabine), biologic therapies (i.e., lenalidomide, rigosertib) and hematopoietic cell transplant are permissible;
• Performance status must be Eastern Cooperative Oncology Group (ECOG) 0, 1, or 2;

• Women of child-bearing potential (i.e., women who are pre-menopausal or not surgically sterile) may participate, provided they meet the following conditions:

  • Must agree to use physician-approved contraceptive methods throughout the study and for three months following the last dose of omacetaxine and
  • Must have a negative serum or urine pregnancy test within 7 days prior to beginning treatment on this trial;
• Males with female partners of child-bearing potential must agree to use physician-approved contraceptive methods throughout the study and should avoid conceiving a child for 6 months following the last dose of omacetaxine.

Exclusion Criteria:

• Subjects who are eligible for hematopoietic stem cell transplant;
• History of atrial fibrillation related to azanucleoside therapy in the past;
• Active, uncontrolled, clinically significant infection;
• Pregnant and nursing patients are excluded because the effects of omacetaxine on a fetus or nursing child are unknown;
• Treatment with any anticancer therapy (standard or investigational) within the previous 14 days prior to the first dose of study drug or less than full recovery from the clinically significant toxic effects of that treatment.

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: Arm 1; Omacetaxine - escalating doses subcutaneous twice daily on Days 1-5 and 8-12 Azacitidine 50 mg/m2 subcutaneous/intravenous daily on Days 8-12 G-CSF 5mcg/kg subcutaneous daily on Days 15-19 and 22-26	Drug: Omacetaxine; Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF; Other Names: Synribo; Drug: Azacitidine; Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF; Other Names: Vidaza; Drug: G-CSF; Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF; Other Names: Neupogen

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The maximum tolerated dose (MTD) of omacetaxine in combination with azacitidine and G-CSF in patients with relapsed and/or refractory low- and intermediate-risk MDS.	28 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Number of participants with Hematologic Improvement (HI) as measured by hemoglobin, platelet count and neutrophil count.	12 months
Number of participants with disease response as defined by International Working Group (IWG) 2006 criteria.	12 months
Number of participants who achieve complete remission and how long the response lasts	24 months
Length of time of survival for participants	24 months
Incidences of Grade 3/4 adverse events directly related to the drug combination	24 months

Other Outcome Measures

Outcome Measure	Time Frame
Number of participants who demonstrate changes in chromosome karyotype and genetic mutations	12 months

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: Teva Pharmaceutical Industries, Ltd.
• Investigators: Principal Investigator: Maxim N. Norkin, MD, PhD, University of Florida

Study record dates

Study Major Dates

• Study Start: August 1, 2016
• Primary Completion (ANTICIPATED): December 1, 2018
• Study Completion (ANTICIPATED): December 1, 2018

Study Registration Dates

• First Submitted: June 30, 2016
• First Submitted That Met QC Criteria: July 13, 2016
• First Posted (ESTIMATE): July 18, 2016

Study Record Updates

• Last Update Posted (ACTUAL): May 3, 2017
• Last Update Submitted That Met QC Criteria: May 1, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Myelodysplastic Syndromes
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Protein Synthesis Inhibitors; Azacitidine; Homoharringtonine
• Other Study ID Numbers: IRB201601194; UF-MDS-OAG-101 (OTHER: UF)

Drug and device information, study documents

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