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Myelofibrosis Transformation in Essential ThrombocythemiaPhase 2NCT04054245

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

A Phase 2 study testing LOXL2 Inhibitor PAT-1251, Quality-of-Life Assessment and Questionnaire Administration in people with Myelofibrosis Transformation in Essential Thrombocythemia and Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, run by M.D. Anderson Cancer Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
LOXL2 Inhibitor PAT-1251, Quality-of-Life Assessment and Questionnaire Administration
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
24 Jul 2019to 24 Jul 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 11Show fewer
  • 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)

Who cannot join

  • 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
  • Presence of unstable atrial fibrillation (ventricular response > 100 beats per minute [bpm]); patients with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria
  • Clinically significant resting bradycardia (< 50 bpm)
  • Angina pectoris or acute myocardial infarction =< 3 months prior to starting study drug
Show all 19Show fewer
  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • M D Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Open Label Phase 2 Single Agent Study of PAT-1251 in Patients With Primary Myelofibrosis (PMF), Post-Polycythemia Vera Myelofibrosis (Post-PV MF), or Post-Essential Thrombocytosis Myelofibrosis (Post-ET MF)

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
LOXL2 Inhibitor PAT-1251, Quality-of-Life Assessment, Questionnaire Administration
Medical subject headings
Polycythemia Vera, Primary Myelofibrosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LOXL2 Inhibitor PAT-1251Drug

    Also called PAT-1251; PAT1251; PAT 1251; Lysyl Oxidase-like Protein 2 Inhibitor PAT-1251

    Given PO

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04054245
Study groupRoleWhat they receive
Treatment (LOXL2 inhibitor PAT-1251)ExperimentalPatients 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.
Receives: Drug: LOXL2 Inhibitor PAT-1251; Other: Quality-of-Life Assessment; Other: Questionnaire Administration

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Up to 6 cycles, each cycle is 28 days.

Secondary outcomes (10)

  1. 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.

    Measured: Up to 2 years

  2. Time to response

    The distribution will be estimated by Kaplan-Meier curves.

    Measured: 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

  3. Duration of response

    The distribution will be estimated by Kaplan-Meier curves.

    Measured: 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

  4. Changes in symptom burden

    Will be assessed by Myeloproliferative Neoplasm Symptom Assessment Form Total Symptom Score.

    Measured: Baseline up to 2 years

  5. 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.

    Measured: Baseline up to 2 years

  6. 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.

    Measured: Baseline up to 2 years

  7. 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.

    Measured: Baseline up to 2 years

  8. 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.

    Measured: Baseline up to 2 years

  9. Proportion of transfusion dependent patients who become transfusion independent and have a 1 g/dL increase in hemoglobin

    Will be summarized.

    Measured: Baseline up to 2 years

  10. Proportion of transfusion independent patients requiring a transfusion

    Will be summarized.

    Measured: Baseline up to 2 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Aug 2019
  2. Study start24 Jul 2019
  3. Primary completion24 Jul 2019
  4. Study completion24 Jul 2019

Why it stopped: "Company is in a process of being taken over by another pharma and the new one has different ideas on how to pursue studies with this drug"

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04054245
Sponsor's protocol ID
2018-0831
Other IDs
NCI-2019-03143, 2018-0831, P30CA016672
Status last verified
Aug 2019
First submitted
6 Jun 2019
Last updated
13 Aug 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing LOXL2 Inhibitor PAT-1251, Quality-of-Life Assessment and Questionnaire Administration in people with Myelofibrosis Transformation in Essential Thrombocythemia and Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, run by M.D. Anderson Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 11 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 13 Aug 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Objective response rate (ORR) (time frame: Up to 6 cycles, each cycle is 28 days.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04054245.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Aug 2019.

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