Study of FF-10501-01 in Patients With Relapsed or Refractory Hematological Malignancies

A Phase 1/2a, Dose Escalation Study of FF-10501-01 for the Treatment of Advanced Hematologic Malignancies

A Phase 1/2a Dose Escalation Study of FF-10501-01 in Patients with Relapsed or Refractory Hematological Malignancies to determine the safety and tolerability. A total of 6 cohorts will be enrolled in Phase 1 to establish the MTD. A total of 20 subjects with MDS/CMML treated at the RP2D are planned, including MDS/CMML subjects treated at the RP2D in Phase 1.

Study Overview

• Status: Completed
• Conditions: AML; MDS; CMML
• Intervention / Treatment: Drug: FF-10501-01

Detailed Description

Subjects will receive FF-10501-01 orally on a twice daily schedule for 14, 21 or 28 days repeated every 28 days (=1 cycle). Disease assessments, including analysis of blood and bone marrow aspirates, will be performed at the end of Cycle 1 and every 2 cycles thereafter. Subjects who demonstrate objective response or stable disease will be allowed to continue therapy with FF-10501-01 until progression of disease, observation of unacceptable adverse events, intercurrent illness or changes in condition that prevent further study participation.

• Study Type: Interventional
• Enrollment (Actual): 55
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic at Taussig Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed advanced hematologic malignancies;

Phase 1:

• High-risk MDS/CMML (defined as ≥ 10% peripheral blood or marrow blasts and/or IPSS score ≥ 1.5) and relapsed or refractory to prior therapy
• AML relapsed or refractory to prior therapy, or ≥ 60 years of age and not a candidate for other therapies

Phase 2a:

• MDS/CMML, relapsed from, or refractory to, prior HMA therapy; the latter defined as failure to achieve clinical remission (CR), partial remission (PR) or hematologic improvement (HI) after previous HMA therapy (≥ 4 cycles of azacitidine or decitabine), or progression during, or toxicity to previous HMA therapy precluding further HMA treatment, and,

• Bone marrow blast count ≥ 10% or peripheral blast count ≥ 5%, or IPSS-R score ≥ 3.5.

  • At least 3 weeks beyond the last chemotherapy, targeted anticancer agent, major surgery or experimental treatment and recovered from all acute toxicities (≤ Grade 1). Hydroxyurea used to control peripheral blast counts is permitted up to Day 7 of treatment on study.
  • Adequate performance status: ECOG ≤ 2;
  • Adequate renal and hepatic function:
• creatinine ≤ 2.0 mg/dL, or calculated creatinine clearance ≥ 45 mL/min
• total bilirubin ≤ 2 times the upper limit of normal (ULN)

• ALT/AST ≤ 2 times ULN

  • Negative serum pregnancy test
  • Ability to provide written informed consent

Exclusion Criteria:

• Known history of coronary artery disease, angina, myocardial infarction, congestive heart failure, cardiac arrhythmia or any other type of heart disease present within the last 6 months
• Known family history of hereditary heart disease
• QT interval corrected for rate (QTc) > 450 msec on the electrocardiogram (ECG) obtained at Screening
• Concomitant medication(s) that may cause QTc prolongation or induce Torsades de Pointes, with the exception of anti-microbials that are used as standard of care to prevent or treat infections and other such drugs that are considered by the Investigator to be essential for the care of the patient.
• Presence of active central nervous system (CNS) leukemia. Subjects adequately treated for CNS leukemia documented by 2 consecutive cerebrospinal fluid samples negative for leukemia cells are eligible. Subjects with no history of CNS leukemia will not be required to undergo cerebrospinal fluid sampling for eligibility.
• Known positive for HIV, hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV).
• Active infection requiring IV anti-infective usage within the last 7 days prior to study treatment.
• Any other medical intervention or condition which could compromise adherence to study requirements or confound the interpretation of study results.
• Pregnant or breast-feeding.
• Treatment with any investigational product within 28 days prior to Screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1 Cohort 1: 50mg/m2; FF-10501-01 tablets BID every 14 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 1 Cohort 2: 100mg/m2; FF-10501-01 tablets BID every 14 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 1 Cohort 3: 200mg/m2; FF-10501-01 tablets BID every 14 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 1 Cohort 4: 300mg/m2; FF-10501-01 tablets BID every 14 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 1 Cohort 5: 400mg/m2; FF-10501-01 tablets BID every 14 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 1 Cohort 6: 500mg/m2; FF-10501-01 tablets BID every 14 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 2a Cohort 7: 400mg/m2 in MDS/CMML; FF-10501-01 tablets BID every 21 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 1 Cohort 8: 400mg/m2; FF-10501-01 tablets BID every 28 days of a 28 day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01
Experimental: Phase 2a Cohort 9: 400mg/m2; FF-10501-01 tablets BID every 21 days of a 28-day cycle.	Drug: FF-10501-01; FF-10501-01 will be administered orally on Days 1-14 of a 28-day cycle (Cohorts 1-6), Days 1-21 of a 28-say cycle (Cohort 7), Days 1-28 of a 28-day cycle (Cohort 8) or Days 1-21 of a 28-say cycle (Cohort 9). The dose-escalation will proceed until Maximum Tolerated Dose (MTD) is reached. The treatment will continue until disease progression, intolerable toxicity or investigation/subject decision.; Other Names: Single Group Assignment; Drug FF-10501-01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessed by Adverse Events	Safety and tolerability assessed by adverse events (AEs), serious adverse events (SAEs), dose-limiting toxicity (DLT), dose reductions, delays or withdrawals due to toxicity	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Determination of Objective Response (OR) Rates.	The OR endpoint: proportion of subjects w/ OR as best response (CR, CRi or PR) assessed at the end of Cycles 1 and 3. AML: CR - free of all symptoms related to leukemia, absolute neutrophil count > 1.0 x 10^9/L, platelet count ≥ 100 x 10^9/L, normal bone marrow with < 5% blasts no Auer rods; CRi - CR with residual thrombocytopenia (platelet count < 100 x 10^9/L) or residual neutropenia (absolute neutrophil count < 1.0 x 10^9/L); PR - A ≥ 50% decrease in bone marrow blasts to 5 to 25% abnormal. MDS or CMML: CR - free of all symptoms related to leukemia, absolute neutrophil count ≥ 1.0 x 10^9/L, platelet count ≥ 100 x 10^9/L, bone marrow ≤ 5% myeloblasts, w/ normal maturation of all cell lines, hemoglobin ≥ 11g/dL, no blasts in the peripheral blood; PR - All CR criteria with ≥50% decrease in bone marrow blasts over pre-treatment (but still > 5%); Marrow CR - In bone marrow, ≤ 5% myeloblasts and decrease by ≥ 50% over pre-treatment.	OR responses were assessed at end of Cycles 1 thru 3. Each cycle was 28 days in length.

Collaborators and Investigators

• Sponsor: Fujifilm Pharmaceuticals U.S.A., Inc.
• Investigators: Principal Investigator: Guillermo Garcia-Manero, MD, M.D. Anderson Cancer Center

Publications and helpful links

General Publications

• Garcia-Manero G, Pemmaraju N, Alvarado Y, Naqvi K, Ravandi F, Jabbour E, De Lumpa R, Kantarjian H, Advani A, Mukherjee S, Gerds A, Carraway HE, Nazha A, Iwamura H, Murase M, Bavisotto L, Kurman M, Maier G, Johansen M, Sekeres MA. Results of a Phase 1/2a dose-escalation study of FF-10501-01, an IMPDH inhibitor, in patients with acute myeloid leukemia or myelodysplastic syndromes. Leuk Lymphoma. 2020 Aug;61(8):1943-1953. doi: 10.1080/10428194.2020.1747065. Epub 2020 Apr 7.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): August 9, 2019
• Study Completion (Actual): October 15, 2019

Study Registration Dates

• First Submitted: July 14, 2014
• First Submitted That Met QC Criteria: July 16, 2014
• First Posted (Estimated): July 18, 2014

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 13, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Acute Myeloid Leukemia; Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: FF1050101US01

Plan for Individual participant data (IPD)

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