A Study of FF-10501-01 in Combination With Azacitidine in Patients With Myelodysplastic Syndrome

Study Overview
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Brief Summary
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The primary objective of the study is to determine the response rate according to the International Working Group Response criteria for the combination of FF-10501-01 and azacitidine in patients previously untreated with hypomethylating agents, with Int2/High risk MDS according to the IPSS, and Intermediate/High/Very-High risk MDS according to the IPSS-R, or who are otherwise candidates for treatment with azacitidine.

Detailed Description
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This is an open-label, Simon 2-stage clinical study of the combination of FF-10501-01 and azacitidine in previously untreated patients with high-risk MDS, or in patients with myelodysplastic syndrome (MDS) who are otherwise candidates for treatment with azacitidine in the judgment of the Investigator. The Phase 2 portion of the trial will be preceded by a Phase 1 run-in to evaluate the safety of the combination of FF-10501-01 plus azacitidine.

Official Title
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A Phase 2 Study of FF-10501-01 in Combination With Azacitidine in Patients With Myelodysplastic Syndrome

Conditions
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Myelodysplastic Syndrome (MDS)

Intervention / Treatment
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* Drug: FF-10501-01
* Drug: Azacitidine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients ≥ 18 years of age MDS as determined by bone marrow aspirate and/or biopsy according to the WHO Classification within 6 weeks of the first dose of study medication, with bone marrow blast counts of < 20%. Int2/High-risk MDS according to the IPSS, Intermediate/high/very high-risk MDS according to the IPSS-R, or otherwise eligible for treatment with azacitidine in the judgment of the Investigator ECOG Performance Score of 0 or 1 Adequate hepatic function as evidenced by AST/ALT < 3X the ULN and total bilirubin < 2X the ULN for the reference lab Adequate renal function as evidenced by serum creatinine < 2 mg/dL or a calculated creatinine clearance of > 50 mL/min Exclusion Criteria: A current infection requiring treatment with intravenous antibiotics, anti-fungal agents, or anti-viral agents Previous treatment with a hypomethylating agent, an HDAC inhibitor, or any other drug intended for the treatment of MDS other than hematopoietic growth factors, immunosuppressive therapy or hydroxyurea. Patients with 5q deletions may have received prior lenalidomide. Use of hematopoietic growth factors (erythropoietin, G-CSF, GM-CSF, thrombopoietin receptor agonists) or immunosuppressive treatments within 7 days of first dose of study medication Administration of any investigational agent within 5 half-lives of the agent; if the half-life is not known, use of such an agent within 2 weeks of the first dose of study medication Active infection with HIV or hepatitis B or C; patients with a history of such disorders should undergo serological testing to evaluate the activity of the infection

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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: open-label, Simon 2-stage clinical study of the combination of FF-10501-01 and azacitidine in MDS patients. The Phase 2 portion of the trial will be preceded by a Phase 1 run-in to evaluate the safety of the combination of FF-10501-01 plus azacitidine.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Run-In Phase, Regimen 1<br>Patients will be treated with FF-10501-01 at a dose of 400 mg/m2 twice daily (BID) for 14 days plus azacitidine at a dose of 75 mg/m2 either subcutaneously (SC) or intravenously (IV) x 7 days every 28 days. One treatment cycle will be 28 days in duration. | Drug: FF-10501-01<br>* FF-10501-01 round film-coated tablets are immediate release and come in 3 dosage strengths: 50 mg (tan), 100 mg tablets (red) and 200 mg (yellow). Each tablet contains the active ingredient (FF-10501-01 white crystalline powder) and other excipients. All dosage strengths are packaged 32 tablets to a bottle. FF-10501-01 should be stored at room temperature (20 - 25 °C).<br>Drug: Azacitidine<br>* azacitidine at a dose of 75 mg/m2 either subcutaneously (SC) or intravenously (IV) x 7 days every 28 days<br>|
| Experimental: Run-In Phase, Regimen 2<br>Patients will be treated with FF-10501-01 at a dose of 400 mg/m2 BID for 21 days plus azacitidine at a dose of 75 mg/m2 either SC or IV x 7 days every 28 days. | Drug: FF-10501-01<br>* FF-10501-01 round film-coated tablets are immediate release and come in 3 dosage strengths: 50 mg (tan), 100 mg tablets (red) and 200 mg (yellow). Each tablet contains the active ingredient (FF-10501-01 white crystalline powder) and other excipients. All dosage strengths are packaged 32 tablets to a bottle. FF-10501-01 should be stored at room temperature (20 - 25 °C).<br>Drug: Azacitidine<br>* azacitidine at a dose of 75 mg/m2 either subcutaneously (SC) or intravenously (IV) x 7 days every 28 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response Rate | The primary efficacy assessment will be the objective response rate, composed of those patients who achieve a best response of CR, mCR, PR or HI based on the Modified IWG Response Criteria in MDS | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hematologic Improvement Rate | Determination of the hematologic improvement rate for erythroid, platelet and/or neutrophil response. The number of patients who achieve trilineage hematologic improvement will be reported, as will the number who achieve improvement in each of the cell series (i.e., erythroid (HI-E), platelet (HI-P), and/or neutrophil (HI-N). | 24 months | 
| Duration of Response | Duration of response will be measured from the date of initial response until failure (includes death from any cause), relapse (after CR or PR) or progression, as defined by the Modified IWG Response Criteria in MDS. | 24 months | 
| Event-Free Survival | Duration of event free survival will be measured from the start of treatment until failure (as defined in the Modified IWG Response Criteria) or death from any cause. | 24 months | 
| Progression-Free Survival | Duration of progression free survival will be measured from the start of treatment until progression (as defined in the Modified IWG Response Criteria) or death from MDS. | 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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myelodysplastic syndrome (MDS)