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

Study Overview
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Brief Summary
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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.

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

Conditions
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Myelodysplastic Syndromes

Intervention / Treatment
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* Drug: Omacetaxine
* Drug: Azacitidine
* Drug: G-CSF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1<br>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<br>* Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF<br>* Other names: Synribo;Drug: Azacitidine<br>* Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF<br>* Other names: Vidaza;Drug: G-CSF<br>* Comparison of different doses of omacetaxine in combination with azacitidine and G-CSF<br>* Other names: Neupogen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 | Measure Description | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myelodysplastic Syndromes