Myelodysplastic Syndrome (MDS)
Conditions
Keywords
myelodysplastic syndrome (MDS)
Brief summary
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
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.
Interventions
DRUGFF-10501-01
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).
DRUGAzacitidine
azacitidine at a dose of 75 mg/m2 either subcutaneously (SC) or intravenously (IV) x 7 days every 28 days
Sponsors
Fujifilm Pharmaceuticals U.S.A., Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Male or female patients ≥ 18 years of age 2. 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%. 3. 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 4. ECOG Performance Score of 0 or 1 5. Adequate hepatic function as evidenced by AST/ALT \< 3X the ULN and total bilirubin \< 2X the ULN for the reference lab 6. Adequate renal function as evidenced by serum creatinine \< 2 mg/dL or a calculated creatinine clearance of \> 50 mL/min
Exclusion criteria
1. A current infection requiring treatment with intravenous antibiotics, anti-fungal agents, or anti-viral agents 2. 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. 3. 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 4. 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 5. 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Response Rate | 24 months | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Hematologic Improvement Rate | 24 months | 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). |
| Duration of Response | 24 months | 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. |
| Event-Free Survival | 24 months | 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. |
| Progression-Free Survival | 24 months | 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. |
Outcome results
None listed