PAT-1251 in Treating Patients With Primary Myelofibrosis, Post-Polycythemia Vera Myelofibrosis, or Post-Essential Thrombocytosis Myelofibrosis

NCT ID: NCT04054245

Last Updated: 2019-08-13

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-24
• Study Completion Date: 2019-07-24

Brief Summary

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.

Detailed Description

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.

Conditions

Myelofibrosis Transformation in Essential Thrombocythemia; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment (LOXL2 inhibitor PAT-1251)

Patients receive LOXL2 inhibitor PAT-1251 PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Group Type: EXPERIMENTAL

LOXL2 Inhibitor PAT-1251

Intervention Type: DRUG

Given PO

Quality-of-Life Assessment

Intervention Type: OTHER

Ancillary studies

Questionnaire Administration

Intervention Type: OTHER

Ancillary studies

Interventions

LOXL2 Inhibitor PAT-1251

Given PO

Intervention Type: DRUG

Quality-of-Life Assessment

Ancillary studies

Intervention Type: OTHER

Questionnaire Administration

Ancillary studies

Intervention Type: OTHER

Other Intervention Names

PAT-1251; PAT1251; PAT 1251; Lysyl Oxidase-like Protein 2 Inhibitor PAT-1251; Quality of Life Assessment

Eligibility Criteria

Inclusion Criteria

• Patients must provide written informed consent
• Willing and able to comply with scheduled visits, treatment plan and laboratory tests
• Patient is able to swallow and retain oral medication
• Must be diagnosed with treatment requiring PMF or post ET/PV MF with intermediate -1, intermediate -2 or high risk disease according to the International Working Group (IWG) prognostic scoring system, or if with low risk disease then with symptomatic splenomegaly that is greater than or equal to 5 cm below left costal margin by physical exam
• Patients who are not candidates for, intolerant of, or relapsed/refractory to ruxolitinib
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2
• Absolute neutrophil count (ANC) >= 1.5 x 10^9/L (1500/mm^3)
• Serum direct bilirubin =< 2.0 x ULN (upper limit of normal)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) or alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) (if both measured, then this applies to both measurements) =< 2.5 x ULN, except for patients with MF involvement of the liver who must have levels =< 5 x ULN
• Treatment-related toxicities from prior therapies must have resolved to grade =< 1
• At least 2 weeks from prior MF-directed treatment (till the start of study drug)

Exclusion Criteria

• Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities
• Impaired cardiac function or clinically significant cardiac diseases, including any of the following:

• History or presence of ventricular tachyarrhythmia
• Clinically significant resting bradycardia (< 50 bpm)
• Angina pectoris or acute myocardial infarction =< 3 months prior to starting study drug
• Other clinically significant heart disease (e.g., symptomatic congestive heart failure; uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen)
• Patients who are currently receiving chronic (> 14 days) treatment with corticosteroids at a dose >= 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug
• Patients with impairment of gastrointestinal (GI) function or GI disease that may significantly alter the absorption of PAT-1251 as per physicians opinion
• Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive - human chorionic gonadotropin (HCG) laboratory test
• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during dosing and for 90 days after study treatment. Highly effective contraception methods include:

• Total abstinence or
• Male partner or female sterilization or
• Combination of any two of the following (a+b or a+c, or b+c):

• Use of oral, injected or implanted hormonal methods of contraception
• Placement of an intrauterine device (IUD) or intrauterine system (IUS)
• Barrier methods of contraception: condom for male partner or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository
• Note: Postmenopausal women are allowed to participate in this study. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate, history of asomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, a woman is considered to be of not child bearing potential only when her reproductive status has been confirmed by follow-up hormone level assessment
• Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping study drug and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: collaborator

M.D. Anderson Cancer Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lucia Masarova

Role: PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Locations

M D Anderson Cancer Center

Houston, Texas, United States

Countries

United States

Related Links

http://www.mdanderson.org

MD Anderson Cancer Center Website

Other Identifiers

NCI-2019-03143

Identifier Type: REGISTRY

Identifier Source: secondary_id

2018-0831

Identifier Type: OTHER

Identifier Source: secondary_id

P30CA016672

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2018-0831

Identifier Type: -

Identifier Source: org_study_id