Clinical Trials /

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

NCT02193958

Description:

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.

Related Conditions:
  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndromes
Recruiting Status:

Active, not recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of FF-10501-01 in Patients With Relapsed or Refractory Hematological Malignancies
  • Official Title: A Phase 1/2a, Dose Escalation Study of FF-10501-01 for the Treatment of Advanced Hematologic Malignancies

Clinical Trial IDs

  • ORG STUDY ID: BS FF1050101US01
  • NCT ID: NCT02193958

Conditions

  • AML
  • CMML
  • MDS

Interventions

DrugSynonymsArms
FF-10501-01Single Group Assignment, Drug FF-10501-01Phase 1: Lowest dose of FF-10501-01

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Phase 1: Lowest dose of FF-10501-01ExperimentalFF-10501-01 tablets BID every 14 days of a 28 day cycle.
  • FF-10501-01
Phase 1: 2x lowest dose of FF-10501-01Experimental2x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
  • FF-10501-01
Phase 1: 4x lowest dose of FF-10501-01Experimental4x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
  • FF-10501-01
Phase 1: 6x lowest dose of FF-10501-01Experimental6x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
  • FF-10501-01
Phase 1: 8x lowest dose of FF-10101-01Experimental8x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
  • FF-10501-01
Ph 2a: FF-10501-01 at 8x in MDS/CMMLExperimentalFF-10501-01 tablets BID every 21 days of a 28 day cycle.
  • FF-10501-01
Ph1:8x lowest dose FF10101-01 for 21 dayExperimentalFF-10501-01 tablets BID every 21 days of a 28 day cycle.
  • FF-10501-01
Ph1: 8x lowest dose FF-10101-01 28 dayExperimentalFF-10501-01 tablets BID every 28 days of a 28 day cycle.
  • FF-10501-01
Ph1: 10X lowest dose FF-10501-01 14 dayExperimental10x lowest dose of FF-10501-01 tablets BID every 14 days of a 28 day cycle.
  • 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.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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

Secondary Outcome Measures

Measure:Determination of overall response rates.
Time Frame:Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
Safety Issue:
Description:Response criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects)
Measure:Evaluate the pharmacokinetic profile of FF-10501-01 and its metabolite.
Time Frame:Evaluated at three timepoints: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1. Each cycle is 28 days in length.
Safety Issue:
Description:Cmax, Tmax, Half-life, AUC, Clearance, Volume of Distribution
Measure:Changes from baseline in xanthosine monophosphate (XMP) as a pharmacodynamic marker.
Time Frame:Evaluated at three timepoints: Cycle 1 Day 1, Cycle 1 Day 15, Cycle 2 Day 1. Each cycle is 28 days in length.
Safety Issue:
Description:Xanthosine monophosphate (XMP)
Measure:Evaluate the proportion of subjects who achieve hematologic improvement in peripheral blood or bone marrow blast count.
Time Frame:Responses and survival assessed at the end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
Safety Issue:
Description:Response Criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).
Measure:Evaluate progression-free survival (PFS).
Time Frame:Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
Safety Issue:
Description:Response Criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).
Measure:Evaluate overall survival (OS).
Time Frame:Responses and survival assessed at end of Cycle 1 and every 2 cycles thereafter through 6 months following last dose of study drug. Each cycle is 28 days in length.
Safety Issue:
Description:Response criteria by IWG Response Criteria for AML (AML subjects) or IWG Response Criteria for MDS (MDS and CMML subjects).

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Fujifilm Pharmaceuticals U.S.A., Inc.

Trial Keywords

  • Acute Myeloid Leukemia
  • Chronic Myelomonocytic Leukemia
  • Myelodysplastic Syndrome

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