Study of a Novel BET Inhibitor FT-1101 in Patients With Relapsed or Refractory Hematologic Malignancies

Acute Myeloid Leukemia Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02543879
• Other study ID #: 1101-HEM-101
• Status: Completed
• Phase: Phase 1
• Start date: September 2015
• Est. completion date: March 2019

Study information

• Verified date: November 2023
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 94
• Est. completion date: March 2019
• Est. primary completion date: March 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Acute Myelogenous Leukemia
• Acute Myeloid Leukemia
• Hematologic Neoplasms
• Leukemia
• Leukemia, Myeloid
• Leukemia, Myeloid, Acute
• Lymphoma, Non-Hodgkin
• Myelodysplastic Syndrome
• Myelodysplastic Syndromes
• Non-Hodgkin Lymphoma
• Preleukemia

Intervention

Drug:
• FT-1101
FT-1101 will be supplied as 5 mg, 20 mg or 100 mg capsules and will be administered per the protocol defined frequency and dose level
• Azacitidine
Azacitidine will be administered per site's standard of care

Locations

Country	Name	City	State
United States	University of Maryland, Greenebaum Comprehensive Cancer Center	Baltimore	Maryland
United States	Levine Cancer Institute	Charlotte	North Carolina
United States	Northwestern University	Chicago	Illinois
United States	MD Anderson Cancer Center	Houston	Texas
United States	Cedars Sinai	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Forma Therapeutics, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of on-target activity of FT-1101, as determined by changes in PD biomarkers in bone marrow aspirates and/or peripheral blood		Assessed for duration of participation, an expected average of 12 weeks
Other	To determine if there is any correlation between cancer-associated genetic alterations with response		Assessed for duration of participation, an expected average of 12 weeks
Other	To evaluate PK/PD relationships in dose-escalation and dose-expansion cohorts		Assessed for duration of participation, an expected average of 12 weeks
Primary	Maximum Tolerated Dose (MTD)		Within first 4 weeks of treatment
Primary	Dose Limiting Toxicities (DLT)		Within first 4 weeks of treatment
Primary	Recommended Phase 2 Dose (RP2D)		Participants to be followed for duration of participation, an expected average of 12 weeks
Secondary	Area under the plasma concentration versus time curve (AUC)		PK collected at multiple visits during the first 30 days of treatment
Secondary	Peak Plasma Concentration (Cmax)		PK collected at multiple visits during the first 30 days of treatment
Secondary	Time of peak plasma concentration (TMax)		PK collected at multiple visits during the first 30 days of treatment
Secondary	Time for half of the drug to be absent in blood stream following dose (T 1/2)		PK collected at multiple visits during the first 30 days of treatment
Secondary	Rate at which drug is removed from blood stream (CL/F)		PK collected at multiple visits during the first 30 days of treatment
Secondary	Rate of drug distribution within the blood stream (Vd/F)		PK collected at multiple visits during the first 30 days of treatment
Secondary	Observe patients for any evidence of anti-leukemic or anti-myelodysplastic activity of FT-1101		Assessed for duration of participation, an expected average of 12 weeks