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

NCT02835794 | Withdrawn Phase 1 DMC FDA Drug

• 2 other identifiers: IRB201601194UF-MDS-OAG-101
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Myelodysplastic Syndromes

Keywords

Myelodysplastic Syndromes

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (5)

• 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 Outcomes (1)

• Number of participants who demonstrate changes in chromosome karyotype and genetic mutations

  12 months

Study Arms (1)

Arm 1

EXPERIMENTAL

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; Drug: Azacitidine; Drug: G-CSF

Interventions

Omacetaxine DRUG

Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF

Also known as: Synribo

Arm 1

Azacitidine DRUG

Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF

Also known as: Vidaza

Arm 1

G-CSF DRUG

Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF

Also known as: Neupogen

Arm 1

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Teva Pharmaceutical Industries, Ltd.: collaborator

Study Sites (1)

University of Florida Health Shands Cancer Hospital

Gainesville, Florida, 32608, United States

Location

MeSH Terms

Conditions

Myelodysplastic Syndromes

Interventions

Homoharringtonine; Azacitidine; Granulocyte Colony-Stimulating Factor; Filgrastim

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; 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; Aza Compounds; Organic Chemicals; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides; Colony-Stimulating Factors; Glycoproteins; Glycoconjugates; Carbohydrates; Hematopoietic Cell Growth Factors; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Maxim N. Norkin, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2016
• First Posted: July 18, 2016
• Study Start: August 1, 2016
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: May 3, 2017

Record last verified: 2017-05

Locations

US (1)