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

NCT ID: NCT02193958

Last Updated: 2025-03-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-31
• Study Completion Date: 2019-10-15

Brief Summary

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.

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.

Conditions

AML; CMML; MDS

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Phase 1 Cohort 1: 50mg/m2

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 1 Cohort 2: 100mg/m2

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 1 Cohort 3: 200mg/m2

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 1 Cohort 4: 300mg/m2

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 1 Cohort 5: 400mg/m2

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 1 Cohort 6: 500mg/m2

FF-10501-01 tablets BID every 14 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 2a Cohort 7: 400mg/m2 in MDS/CMML

FF-10501-01 tablets BID every 21 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 1 Cohort 8: 400mg/m2

FF-10501-01 tablets BID every 28 days of a 28 day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Phase 2a Cohort 9: 400mg/m2

FF-10501-01 tablets BID every 21 days of a 28-day cycle.

Group Type: EXPERIMENTAL

FF-10501-01

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Single Group Assignment; Drug FF-10501-01

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fujifilm Pharmaceuticals U.S.A., Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Guillermo Garcia-Manero, MD

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

Cleveland Clinic at Taussig Cancer Center

Cleveland, Ohio, United States

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 32264726 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

FF1050101US01

Identifier Type: -

Identifier Source: org_study_id