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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Myelodysplastic Syndrome (MDS)
• Intervention / Treatment: Drug: FF-10501-01; Drug: 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.

• Study Type: Interventional
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Run-In Phase, Regimen 1; 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; 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).; Drug: Azacitidine; azacitidine at a dose of 75 mg/m2 either subcutaneously (SC) or intravenously (IV) x 7 days every 28 days
EXPERIMENTAL: Run-In Phase, Regimen 2; 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; 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).; Drug: Azacitidine; azacitidine at a dose of 75 mg/m2 either subcutaneously (SC) or intravenously (IV) x 7 days every 28 days

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): October 1, 2019
• Primary Completion (ANTICIPATED): October 1, 2019
• Study Completion (ANTICIPATED): October 1, 2019

Study Registration Dates

• First Submitted: March 27, 2018
• First Submitted That Met QC Criteria: March 30, 2018
• First Posted (ACTUAL): April 3, 2018

Study Record Updates

• Last Update Posted (ACTUAL): July 27, 2021
• Last Update Submitted That Met QC Criteria: July 20, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: myelodysplastic syndrome (MDS)
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Disease; Bone Marrow Diseases; Hematologic Diseases; Precancerous Conditions; Syndrome; Myelodysplastic Syndromes; Preleukemia; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites, Antineoplastic; Antimetabolites; Antineoplastic Agents; Azacitidine
• Other Study ID Numbers: FF1050101US201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No