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

NCT04054245 | Withdrawn Phase 2 FDA Drug

• 3 other identifiers: 2018-0831NCI-2019-03143P30CA016672
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 6 cycles, each cycle is 28 days.

Secondary Outcomes (10)

• Incidence of adverse events (AEs)

  Up to 2 years

• Time to response

  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

  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

  Baseline up to 2 years

• The Descriptive statistics in the improvement of anemia

  Baseline up to 2 years

Other Outcomes (2)

• The Correlative Studies

  Baseline up to 2 years

• Percent target engagement after treatment

  Baseline up to 2 years

Study Arms (1)

Treatment (LOXL2 inhibitor PAT-1251)

EXPERIMENTAL

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.

Drug: LOXL2 Inhibitor PAT-1251; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

Interventions

LOXL2 Inhibitor PAT-1251 DRUG

Given PO

Also known as: PAT-1251; PAT1251; PAT 1251; Lysyl Oxidase-like Protein 2 Inhibitor PAT-1251

Treatment (LOXL2 inhibitor PAT-1251)

Quality-of-Life Assessment OTHER

Ancillary studies

Also known as: Quality of Life Assessment

Treatment (LOXL2 inhibitor PAT-1251)

Questionnaire Administration OTHER

Ancillary studies

Treatment (LOXL2 inhibitor PAT-1251)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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)

Sponsors & Collaborators

• M.D. Anderson Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

M D Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Links

• MD Anderson Cancer Center Website

MeSH Terms

Conditions

Polycythemia Vera; Primary Myelofibrosis

Condition Hierarchy (Ancestors)

Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Myeloproliferative Disorders

Study Officials

• Lucia Masarova

  M.D. Anderson Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 6, 2019
• First Posted: August 13, 2019
• Study Start: July 24, 2019
• Primary Completion: July 24, 2019
• Study Completion: July 24, 2019
• Last Updated: August 13, 2019

Record last verified: 2019-08

Locations

US (1)