Myeloproliferative Neoplasms Clinical Trial

Study to Evaluate Safety, Pharmacokinetic and Pharmacodynamic Dose Escalation and Expansion Study of PXS-5505 in Patients With Primary, Post-polycythemia Vera or Post-essential Thrombocythemia Myelofibrosis

Summary

This study will be an open-label phase 1/2a study to evaluate the safety and tolerability of PXS-5505 in patients with primary, postpolycythemia vera (PV) or post-essential thrombocythemia (ET) myelofibrosis.

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Full Description

The study consists of two phases: a dose escalation phase and a cohort expansion phase. The dose escalation phase will follow a 3+3 design with a starting dose of 100 mg twice daily, and a treatment duration of 4 weeks. Patients will be able to participate in more than one dose level.

During the cohort expansion phase, up to 24 patients will be treated at the dose determined appropriate based on safety, pharmacokinetic and pharmacodynamic results from the dose escalation phase, for a period of up to 6 months. Patients from the dose escalation phase will be able to participate in the cohort expansion phase.

There will be no washout period between dose escalation and dose expansion cohorts.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria:

Have a pathologically confirmed established diagnosis of primary myelofibrosis or post-essential thrombocythemia/polycythemia vera myelofibrosis as per the World Health Organization 2016 diagnostic criteria (must include at least Grade 2 marrow fibrosis)
Patients who are not eligible for stem cell transplantation

Patients not currently on ruxolitinib or fedratinib (where available) treatment due to ineligibility, or previously treated patients who have been discontinued for at least 2 weeks prior to first dose of study drug due to any of the following criteria:

Ineligible: Platelets <50 x 10^9L
Intolerant: Development of red blood cell transfusion dependence of at least two units/month for 2 months OR ≥Grade 3 adverse events of thrombocytopenia, anemia, hematoma, and/or hemorrhage while on treatment with ruxolitinib or fedratinib for at least 28 days
Refractory: < 10% spleen volume reduction by MRI or CT, or < 30% decrease from baseline in spleen volume by palpation after at least 3 months treatment with ruxolitinib or fedratinib
Relapsed: Regrowth to < 10% spleen volume reduction by MRI or CT, or < 30% decrease from baseline in spleen volume by palpation, following an initial response to ruxolitinib or fedratinib and after at least 3 months treatment
Have intermediate -2, or high-risk disease according to the International Working Group prognostic scoring system (DIPSS);
Have symptomatic disease according to the MFSAF v4.0;
Life expectancy of six months or greater;

Must have adequate organ function as demonstrated by the following (within last 2 weeks):

Alanine aminotransferase and/or aspartate aminotransferase ≤ 2.5x upper limit of normal (ULN), or ≤ 4 x ULN (if upon judgment of the treating physician, it is believed to be due to extramedullary hematopoiesis [EMH] related to MF);
Direct bilirubin ≤ 1.5 x ULN; or ≤ 2 x ULN (if upon judgment of the treating physician, it is believed to be due to EMH related to MF);
Estimated glomerular filtration rate (eGFR) > 50 mL/min
Eastern Cooperative Oncology Group performance status ≤ 2;
Men must agree to using one medically approved contraceptive measure and have their partners agree to an additional barrier method of contraception for the duration of the study and for 90 days after the last administration of study drug; women of childbearing potential must use effective contraception
Cohort Expansion Phase only: A bone marrow biopsy must have been performed within 3 months prior to Day 1 treatment to establish the baseline fibrosis score or within 5 months of the re-initiation of treatment with PXS-5505 if subject participated in dose escalation phase of the trial

Exclusion Criteria:

Greater than (>) 10% blasts in peripheral blood (determined within last two weeks);
Prior splenectomy, or planning to undergo splenectomy, or splenic irradiation within 3 months prior to the first dose of study treatment
Any serious medical condition or psychiatric illness that would prevent (as judged by the treating physician) the subject from signing the informed consent form or any condition, including the presence of laboratory abnormalities, which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from the study
Known history of human immunodeficiency virus, active hepatitis C, or active hepatitis B
History or presence of any form of cancer within the three years prior to enrolment, with the exception of excised basal cell or squamous cell carcinoma of the skin, or cervical carcinoma in situ or breast carcinoma in situ that has been excised or resected completely and is without evidence of local recurrence or metastasis
Participation in an investigational drug or device trial within two weeks prior to study Day 1 or within five times the half-life of the investigational agent in the other clinical study, if known
Use of any cytotoxic chemotherapeutic agents, including hydroxyurea, corticosteroids (prednisone ≤ 10 mg/day or corticosteroid equivalent is allowed), or immune modulators (e.g., thalidomide) within two weeks and interferon use within four weeks prior to study Day 1
Symptomatic congestive heart failure (New York Heart Association Classification Class II), unstable angina, or unstable cardiac arrhythmia requiring medication
Pregnancy
History of surgery within two weeks prior to enrolment or anticipated surgery during the study period or two weeks post-study
History of aneurysm
Any other condition that might reduce the chance of obtaining data required by the protocol or that might compromise the ability to give truly informed consent.

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 1

Estimated Enrollment:

24

Study ID:

NCT04676529

Recruitment Status:

Recruiting

Sponsor:

Pharmaxis

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There are 20 Locations for this study

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Comprehensive Cancer Center (UAB CCC)
Birmingham Alabama, 98374, United States More Info
Vachhani Pankit
Contact
205-934-9591
[email protected]
Harvard U Med School IRB #1
Boston Massachusetts, 02115, United States More Info
Gabriela Hobbs
Contact
617-724-1124
[email protected]
Novant Health Cancer Institute
Winston-Salem North Carolina, 27103, United States More Info
Chen Franklin
Contact
336-277-8800
[email protected]
The University of Texas MD Anderson Cancer Center
Houston Texas, 77030, United States More Info
Masarova Lucia
Contact
832-750-4211
[email protected]
Liverpool Hospital
Liverpool New South Wales, 2170, Australia More Info
Pinky Patel
Contact
0474 279 274
[email protected]
Ashford Cancer Centre Research
Adelaide South Australia, 5037, Australia More Info
Stanley Cheung
Contact
08 8292 2240
[email protected]
One Clinical Research
Perth Western Australia, 6009, Australia More Info
The Perth Blood Institute
West Perth Western Australia, 6005, Australia More Info
Shona Garlick
Contact
61 8 9200 5300
[email protected]
Inje University Busan Paik Hospital - Internal Medicine
Busan Busan Gwang'yeogsi [Pusan-Kwan, 47392, Korea, Republic of More Info
Won Sik Lee
Contact
+82-51-890-6407
[email protected]
Keimyung University Dongsan Medical Center
Daegu Daegu Gwang'yeogsi [Taegu-Kwan, 42601, Korea, Republic of More Info
Young Rok Do
Contact
82-53-250-7114
[email protected]
Gachon University Gil Hospital
Incheon Incheon Gwang'yeogsi [Inch'n-K, 21565, Korea, Republic of More Info
Jae Hoon Lee
Contact
82-460-2186
[email protected]
Seoul National University Hospital
Seoul , 03080, Korea, Republic of More Info
Dong-Yeop Shin
Contact
+82-2-2072-4439
[email protected]
Severance Hospital, Yonsei University Health System- Haemat
Seoul , 03711, Korea, Republic of More Info
June-Won Cheong
Contact
82 2 2228 1970
[email protected]
Samsung Medical Center
Seoul , 06351, Korea, Republic of More Info
Chul Won Jung
Contact
82 2 3410 3452
[email protected]
The Catholic University of Korea, Seoul St. Mary's Hospital
Seoul , 06591, Korea, Republic of More Info
Sung-Eun Lee
Contact
82 2 2258 6058
[email protected]
Chang Gung Medical Foundation - ChiaYi Chang Gung Memorial Hospital - Hematology and Oncology
Chiayi City Chiayi, 613, Taiwan More Info
Chih-Cheng 志丞 Chen 陳
Contact
+886 5 3621000
[email protected]
Kaohsiung Medical University Chung-Ho Memorial Hospital
Kaohsiung , 807, Taiwan More Info
Hui-Hua 惠樺 Hsiao 蕭
Contact
+886-7-312-1101
[email protected]
China Medical University Hospital - Internal Medicine - Taichung
Taichung , 40447, Taiwan More Info
Su-Peng 士芃 Yeh 葉
Contact
+886-4-2205-2121
[email protected]
National Cheng Kung University Hospital - Internal Medicine
Tainan , 70403, Taiwan More Info
Tsai-Yun 彩雲 Chen 陳
Contact
+886 6-2353535
[email protected]
National Taiwan University Hospital - Hematology And Oncology
Taipei , 100, Taiwan More Info
Shang-Ju 尚儒 Wu 吳
Contact
+886-2-23123456
[email protected]

How clear is this clinincal trial information?

Study is for people with:

Myeloproliferative Neoplasms

Phase:

Phase 1

Estimated Enrollment:

24

Study ID:

NCT04676529

Recruitment Status:

Recruiting

Sponsor:


Pharmaxis

How clear is this clinincal trial information?

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