This phase II trial studies how well PAT-1251 works in treating patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytosis myelofibrosis. PAT-1251 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
PRIMARY OBJECTIVES: I. To determine the efficacy of LOXL2 inhibitor PAT-1251 (PAT-1251) as therapy for primary myelofibrosis (PMF), post-polycythemia vera (PV) myelofibrosis (MF), and post-essential thrombocytosis (ET) MF. II. To determine the objective response of PAT-1251 treatment which is defined as CR (complete remission) + PR (partial remission) + CI (clinical improvement) after three and six cycles of treatment. SECONDARY OBJECTIVES: I. To determine the safety of PAT-1251 as therapy for PMF, post-PV MF and post-ET MF. II. To determine time to response and response duration. III. To assess changes in symptom burden as assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score (MPN-SAF TSS). EXPLORATORY OBJECTIVES: I. To explore changes in bone marrow reticulin fibrosis, collagen, osteosclerosis (grading). II. To determine the percent target engagement based on a plasma target engagement assay after treatment with PAT-1251. OUTLINE: Patients receive LOXL2 inhibitor PAT-1251 orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30 days.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Given PO
Ancillary studies
Ancillary studies
M D Anderson Cancer Center
Houston, Texas, United States
Objective response rate (ORR)
Will be defined as complete remission (CR) + partial remission (PR) + clinical improvement (CI). Responses will be categorized according to the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) and European Leukemia Net (ELN) consensus criteria for myelofibrosis. Will be estimated along with the exact 95% confidence interval.
Time frame: Up to 6 cycles, each cycle is 28 days.
Incidence of adverse events (AEs)
Toxicity is defined as grade 3-4 clinically relevant non-hematologic toxicity or a serious adverse event that is at least possibly drug related (Common Terminology Criteria for Adverse Events version 4.03) and occurs anytime during the treatment. The method of Thall, Simon and Estey will be used for toxicity monitoring. Safety data will be summarized by category, severity and frequency. The proportion of patients with AEs will be estimated, along with the Bayesian 95% credible intervals.
Time frame: Up to 2 years
Time to response
The distribution will be estimated by Kaplan-Meier curves.
Time frame: From date of first treatment to the first date at which the subject's objective status was classified as a response (CR, PR, or CI), assessed up to 2 years
Duration of response
The distribution will be estimated by Kaplan-Meier curves.
Time frame: From the date at which the patient's objective status is first noted to be a CR, PR, or CI to the date of progression (no longer meeting criteria for either CR, PR, or CI) is documented (if one has occurred), assessed up to 2 years
Changes in symptom burden
Will be assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.
Time frame: Baseline up to 2 years
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The Descriptive statistics in the improvement of anemia
Will be used to explore improvements in anemia and the following outcomes will be summarized: mean changes in hemoglobin at monthly intervals.
Time frame: Baseline up to 2 years
The Descriptive statistics in Improvements of transfusion dependence.
Will be used to explore improvements in the transfusion dependence. The following outcomes will be summarized: mean changes in hemoglobin at monthly intervals.
Time frame: Baseline up to 2 years
The Transfusion of independent patients
Will be summarized if the patient is not requiring transfusions on the study who experience an increase of 2 g/dL in their hemoglobin.
Time frame: Baseline up to 2 years
Proportion of transfusion dependent patients who become transfusion independent
The proportion of transfusion dependent patients (defined as requiring a transfusion of 2 units packed red blood cells (PRBCs) monthly for 3 months (12 weeks) prior to starting the trial) who become transfusion independent (not requiring a transfusion of PRBCs over a period of 3 months (12 weeks) while on study) will be summarized.
Time frame: Baseline up to 2 years
Proportion of transfusion dependent patients who become transfusion independent and have a 1 g/dL increase in hemoglobin
Will be summarized.
Time frame: Baseline up to 2 years
Proportion of transfusion independent patients requiring a transfusion
Will be summarized.
Time frame: Baseline up to 2 years