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

Sponsor

University of Florida (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02835794

Collaborator

Teva Pharmaceutical Industries, Ltd. (Industry)

Enrollment

Location

Arm

Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelodysplastic Syndromes	Drug: Omacetaxine Drug: Azacitidine Drug: G-CSF	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Aug 1, 2016

Anticipated Primary Completion Date :

Dec 1, 2018

Anticipated Study Completion Date :

Dec 1, 2018

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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

Number of participants who demonstrate changes in chromosome karyotype and genetic mutations [12 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.