Study of FF-10101-01 in Patients With Relapsed or Refractory Acute Myeloid Leukemia

FujiFilm

Status and phase

Completed

Phase 1

Conditions

AML, Adult

Treatments

Drug: FF-10101-01

Study type

Interventional

Funder types

Industry

Other

Identifiers

NCT03194685

FF-10101-US101

Details and patient eligibility

About

A Phase 1 dose escalation and dose ranging study of FF-10101-01 in subjects with relapsed or refractory acute myeloid leukemia to determine the safety, tolerability, PK and preliminary efficacy. A total of 9 cohorts will be enrolled in Phase 1 to establish the Maximum Tolerated Dose (MTD).

Full description

Subjects will receive FF-10101-01 orally once a day repeated every 28 days =1 cycle Frequent blood draws will be collected to measure pharmacodynamic parameters and pharmacodynamic activity.

Disease assessments, including bone marrow aspirates, will be performed at the beginning of cycles 1-3, and every 3 months thereafter. Subjects who demonstrate objective response or stable disease will be allowed to continue therapy with FF-10101-01 until , observation of unacceptable adverse events, or until the subject is no longer deriving benefit based on the opinion of the investigator.

Enrollment

97 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Subjects who are able and willing to give written informed consent

Documented primary or secondary AML, as defined by the WHO criteria (2008), by histopathology refractory to previous induction chemotherapy and/or relapsed after achieving remission with a prior chemotherapy and who are not candidates for other available therapy likely to confer clinical benefit.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2
In the absence of rapidly progressing disease, the interval from prior treatment to time of FF-10101-01 administration should be at least 14 days for cytotoxic agents other than hydroxyurea, at least 5 half-lives for non-cytotoxic agents, and 14 days for monoclonal antibody therapies. Hydroxyurea may be continued for a maximum of 14 days from the start of FF-10101-01 dosing, through Cycle 1 Day 14, with a maximal dose of 5 grams/day
Persistent chronic clinically significant toxicities from prior chemotherapy or surgery must be ≤Grade 2
If subject has had a hematopoietic stem cell transplant, subject must be ≥60 days post-transplant with no clinically significant GVHD requiring systemic therapy
Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤3 times the upper limit of normal and total bilirubin of ≤1.5x the upper limit of normal. If total bilirubin is equal to or exceeds 1.5x the upper limit of normal, the subject can still be included if direct bilirubin is ≤1.5x the upper limit of normal
Calculated creatinine clearance of ≥60 mL/min
Female subjects of childbearing potential and sexually mature male subjects must agree to use a medically accepted method of contraception other than an oral contraceptive for the duration of the study.

Exclusion Criteria:

Subjects diagnosed with acute promyelocytic leukemia
Subjects with Bcr-Abl positive leukemia (chronic myelogenous leukemia in blast crisis)
Subjects with clinically active CNS leukemia
Subjects with major surgery within 28 days prior to the first administration of FF-10101-01
Subjects with radiation therapy within 28 days prior to the first administration of FF-10101-01
Subjects with active malignant disease requiring therapy other than AML or myelodysplastic syndrome with transformation into AML
Subjects with an active uncontrolled infection
Subjects with a medical condition, serious intercurrent illness, or other circumstance that, in the Investigator's judgment, could jeopardize the subject's safety as a study subject, or that could interfere with the study objectives
Subjects known to have human immunodeficiency virus infection, or who have active hepatitis B or C infection as determined by serological testing
Subjects with congestive heart failure, New York Heart Association (NYHA) Class 3 or 4, or subjects with a past history of congestive heart failure NYHA Class 3 or 4 and in whom echocardiogram or multiple gate acquisition (MUGA) scan performed within 3 months prior to screening or at screening showed a LVEF <40%
Female subjects who are pregnant or breast feeding
Subjects on 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) or other drugs known to have muscle toxicity
Subjects taking strong inhibitors of CYP3A4 will be excluded from the study unless therapeutic substitution is possible
Subjects taking strong inducers of CYP3A4 will be excluded from the study unless therapeutic substitution is possible
Use of systemic immunosuppressive agents within 14 days prior to first dose of FF-10101
Subjects taking drugs known to cause Torsades de Pointes will be excluded from the study unless therapeutic substitution is possible
Subjects known to have long QT syndrome
Subjects with mean QTcF values following 3 ECGs conducted 5 minutes apart of >470 msec

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Sequential Assignment

Masking

None (Open label)

97 participants in 8 patient groups

Cohort 1: 10 mg

Experimental group

Description: