A Phase 1/2a, dose-escalation study of FF-10501-01 for the treatment of advanced hematologic malignancies
This is a 2-part study. The goal of Part I of this clinical research study is to find the highest tolerable dose of FF-10501-01 that can be given to patients with refractory or relapsed MDS, CMML, and/or AML. The goal of Part II is to learn if the dose found in Part I can help to control MDS/CMML. The safety of this drug will also be studied.
Disease Group: Leukemia
Treatment Agent: FF-10501-01
Treatment Location: Both at MDACC & and Other Sites
Sponsor: FUJIFILM Pharmaceuticals U.S.A., Inc.
Primary Objective: To determine the safety and tolerability in subjects who receive FF-10501-01 for the treatment of advanced hematologic malignancies Secondary Objective: To determine the overall response rates To evaluate the proportion of subjects who achieve hematologic improvement in peripheral blood or bone marrow blast count To evaluate progression-free survival (PFS) To evaluate overall survival (OS) To evaluate the pharmacokinetics of FF-10501 and M1 To evaluate the xanthosine monophosphate (XMP) as a pharmacodynamic marker
IRB Review and Approval Date: 07/11/2014
Recruitment Status: Open
Projected Accrual: 68
1) Males and females >/= 18 years of age
2) Subjects with confirmed hematologic malignancies: Phase 1: High-risk MDS/CMML (defined as >/= 10% peripheral blood or marrow blasts and/or International Prognostic Scoring System [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.
3) At least 3 weeks beyond the last chemotherapy, targeted anticancer agent, major surgery or experiment 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.
4) Adequate performance status: Eastern Cooperative Oncology Group (ECOG) </= 2
5) Adequate renal and hepatic function: Creatinine </= 2.0 mg/dL, or calculated creatinine clearance >/= 45 mL/minute per the Cockcroft-Gault formula; Total bilirubin </= 2 times the upper limit of normal (ULN); ALT/AST </= 2 times ULN
6) Negative serum pregnancy test within 14 days prior to first dose of study therapy for women of child-bearing potential (WCBP), defined as a sexually mature woman who has not undergone a hysterectomy or who has not been naturally post-menopausal for at least 24 consecutive months (i.e., who has had menses any time in the preceding 24 consecutive months). Sexually active WCBP and male subjects must agree to use adequate methods to avoid pregnancy (oral, injectable, or implantable hormonal contraceptive; tubal ligation; intra-uterine device; barrier contraceptive with spermicide; or vasectomized partner) throughout the study and for 28 days after the completion of the study treatment.
7) Ability to provide written informed consent
1) Known history of active coronary artery disease, angina, myocardial
infarction, or 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
2) 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.
3) Any other medical intervention or other condition which, in the opinion of the Principal Investigator, could compromise adherence with study requirements
4) Known positive for human immunodeficiency virus (HIV), hepatitis B virus surface antigen (HBsAg), or hepatitis C virus (HCV)
5) Active infection requiring intravenous (IV) anti-infective usage within the last 7 days prior to study treatment
6) Pregnant or breast-feeding
7) Treatment with any investigational product within 28 days prior to Screening
Information and next steps
Phase I/Phase II
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