Clinical trial NCT02543879: Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies
Official title: A Phase 1/1b Dose Escalation, Multicenter, Open-label, Safety, Pharmacokinetic and Pharmacodynamic Study of FT-1101 as a Single Agent and in Combination With Azacitidine in Patients With Relapsed or Refractory Hematologic Malignancies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Acute Myeloid Leukemia
Acute Myelogenous Leukemia
Myelodysplastic Syndrome
Non-Hodgkin Lymphoma
Keywords: AML
BET Inhibitor
FT-1101
Acute Leukemia
Myelodysplastic Syndrome
NHL
Non-Hodgkin Lymphoma
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2015-09-07
Enrollment: 94
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is an open-label, multicenter, dose-escalation Phase 1/1b study in patients with acute myelogenous leukemia (AML)/MDS or non-Hodgkin Lymphoma (NHL), intended to investigate safety, pharmacokinetics, and the pharmacodynamic effects of FT-1101 administered via one or more intermittent dosing schedules alone and in combination with azacitidine. Once the MTD has been established for a treatment cohort, up to 20 additional patients may be enrolled in up to 4 expansion cohorts each of select populations of patients with either AML/MDS or NHL at the recommended dose for future studies to confirm safety.


Eligibility criteria: Key Inclusion Criteria:

* Single agent (SA) Dose Escalation: Histologically or cytologically proven acute leukemia or high-risk MDS as defined by the World Health Organization (WHO) criteria and IPSS-R, respectively, that is relapsed or refractory (R/R) to standard therapy or for whom standard treatments are contraindicated, OR
* Mature B-Cell non-Hodgkin Lymphoma that is Relapsed/Refractory to standard therapy
* AML SA expansion group 1: histologically or cytologically proven AML with a FLT3 ITD or TKD mutation previously determined by local testing that is R/R to standard therapy or for whom standard treatments are contraindicated
* AML SA expansion group 2: histologically or cytologically proven AML with intermediate or unfavorable risk cytogenetics in the absence of a detectable FLT3 ITD or TKD mutation as previously determined by local testing that is R/R to standard therapy or for whom standard treatments are contraindicated
* NHL SA expansion: Mature B-cell NHL with the following histologies: primary mediastinal lymphoma, DLBCL, and B-cell lymphoma not specified that is R/R to standard therapy and for whom standard treatments are contraindicated or unavailable
* AML/MDS combination treatment (dose escalation and expansion): histologically or cytologically proven AML or MDS as defined by WHO criteria and IPSS-R, respectively, that is: R/R to standard therapy, or AML: who are unfit for, or unwilling to receive standard induction therapy, or MDS: eligible to receive azacitidine
* Patients ≥ 18 years old
* Good kidney and liver function
* No prior organ allograft
* For fertile men and women, agreement to use effective contraceptive methods duration of study participation and 90 days after

Key Exclusion Criteria:

* History of prior malignancy unless disease free for \> or equal to 12 months or considered surgically cured.
* Patients with symptomatic central nervous system (CNS) metastases or other tumor location (such as spinal cord compression, other compressive mass, uncontrolled painful lesion, bone fracture, etc.) necessitating an urgent therapeutic intervention, palliative care, surgery or radiation therapy
* Treatment with major surgery (requiring general anesthesia) within one month prior to study entry
* Previous treatment with any prior BET inhibitor therapy
* Patients unable to swallow oral medications, or patients with gastrointestinal conditions (e.g. malabsorption, gastric or small bowel resection, etc.) deemed to jeopardize intestinal absorption
* Congestive heart failure (New York Heart Association Class III or IV) or unstable angina pectoris. Previous history of myocardial infarction within 1 year prior to study entry, uncontrolled hypertension or uncontrolled arrhythmias
* Pulmonary disease (e.g. COPD, asthma, etc) that is not controlled (moderate to severe symptoms) with current medication
* Known HIV positivity
* Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy

Primary outcomes:
measure: Maximum Tolerated Dose (MTD)
timeFrame: Within first 4 weeks of treatment
measure: Dose Limiting Toxicities (DLT)
timeFrame: Within first 4 weeks of treatment
measure: Recommended Phase 2 Dose (RP2D)
timeFrame: Participants to be followed for duration of participation, an expected average of 12 weeks
Secondary outcomes:
measure: Area under the plasma concentration versus time curve (AUC)
timeFrame: PK collected at multiple visits during the first 30 days of treatment
measure: Peak Plasma Concentration (Cmax)
timeFrame: PK collected at multiple visits during the first 30 days of treatment
measure: Time of peak plasma concentration (TMax)
timeFrame: PK collected at multiple visits during the first 30 days of treatment
measure: Time for half of the drug to be absent in blood stream following dose (T 1/2)
timeFrame: PK collected at multiple visits during the first 30 days of treatment
measure: Rate at which drug is removed from blood stream (CL/F)
timeFrame: PK collected at multiple visits during the first 30 days of treatment
measure: Rate of drug distribution within the blood stream (Vd/F)
timeFrame: PK collected at multiple visits during the first 30 days of treatment
measure: Observe patients for any evidence of anti-leukemic or anti-myelodysplastic activity of FT-1101
timeFrame: Assessed for duration of participation, an expected average of 12 weeks
Other outcomes:
measure: Assessment of on-target activity of FT-1101, as determined by changes in PD biomarkers in bone marrow aspirates and/or peripheral blood
timeFrame: Assessed for duration of participation, an expected average of 12 weeks
measure: To determine if there is any correlation between cancer-associated genetic alterations with response
timeFrame: Assessed for duration of participation, an expected average of 12 weeks
measure: To evaluate PK/PD relationships in dose-escalation and dose-expansion cohorts
timeFrame: Assessed for duration of participation, an expected average of 12 weeks
Locations:
city: Los Angeles
country: United States
facility: Cedars Sinai
state: California
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Baltimore
country: United States
facility: University of Maryland, Greenebaum Comprehensive Cancer Center
state: Maryland
city: Charlotte
country: United States
facility: Levine Cancer Institute
state: North Carolina
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Houston
country: United States
facility: MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: Forma Therapeutics, Inc.
name: Patrick Kelly, MD
role: STUDY_DIRECTOR
References: