Acute Myelogenous Leukemia, Acute Myeloid Leukemia, Myelodysplastic Syndrome, Non-Hodgkin Lymphoma
Conditions
Keywords
AML, BET Inhibitor, FT-1101, Acute Leukemia, Myelodysplastic Syndrome, NHL, Non-Hodgkin Lymphoma
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.
Interventions
DRUGFT-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
DRUGAzacitidine
Azacitidine will be administered per site's standard of care
Sponsors
Forma Therapeutics, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose Limiting Toxicities (DLT) | Within first 4 weeks of treatment |
| Recommended Phase 2 Dose (RP2D) | Participants to be followed for duration of participation, an expected average of 12 weeks |
| Maximum Tolerated Dose (MTD) | Within first 4 weeks of treatment |
Secondary
| Measure | Time frame |
|---|---|
| Time of peak plasma concentration (TMax) | PK collected at multiple visits during the first 30 days of treatment |
| Rate at which drug is removed from blood stream (CL/F) | PK collected at multiple visits during the first 30 days of treatment |
| Rate of drug distribution within the blood stream (Vd/F) | PK collected at multiple visits during the first 30 days of treatment |
| 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 |
| 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 |
| Area under the plasma concentration versus time curve (AUC) | PK collected at multiple visits during the first 30 days of treatment |
| Peak Plasma Concentration (Cmax) | PK collected at multiple visits during the first 30 days of treatment |
Other
| Measure | Time frame |
|---|---|
| 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 |
| To evaluate PK/PD relationships in dose-escalation and dose-expansion cohorts | Assessed for duration of participation, an expected average of 12 weeks |
| 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 |
Countries
United States
Outcome results
None listed