Pacritinib w/ Talazoparib in Pts w/ Myeloproliferative Neoplasms Unresponsive to JAK2 Inhibition

NCT06218628 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: 23-1048HM-224
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective phase I dose-escalation study, with the primary objective to access the MTD and find the RP2D of talazoparib, given in combination with standard of care dosing of pacritinib.

Conditions

Primary Myelofibrosis; Post-polycythemia Vera Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Chronic Myelomonocytic Leukemia; Polycythemia Vera; Essential Thrombocytosis

Keywords

Talazoparib; Pacritinib; JAK2 Inhibition; Myeloproliferative Neoplasm

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose (MTD)

  To define the maximum tolerated dose (MTD) of talazoparib in combination with standard of care dosing of pacritinib in order to establish a recommended phase II dose (RP2D).

  6 years

Secondary Outcomes (5)

• Rate of grade 3 or higher toxicity

  6 years

• Response rate

  6 years

• Disease control rate

  6 years

• Progression free survival

  6 years

• Overall survival

  6 years

Study Arms (5)

Dose Level -1

EXPERIMENTAL

0.25 mg (PO, QD) Talazoparib (Days 1-7) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

Drug: Talazoparib; Drug: pacritinib

Dose Level 1

EXPERIMENTAL

0.25 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

Drug: Talazoparib; Drug: pacritinib

Dose Level 2

EXPERIMENTAL

0.5 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

Drug: Talazoparib; Drug: pacritinib

Dose Level 3

EXPERIMENTAL

0.75 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

Drug: Talazoparib; Drug: pacritinib

Dose Level 4

EXPERIMENTAL

1 mg (PO, QD) Talazoparib (Days 1-14) 200 mg (PO, BID) Pacritinib (Day 1-28, Lead in dosing of Pacritinib day -7 for the first cycle of treatment)

Drug: Talazoparib; Drug: pacritinib

Interventions

Talazoparib DRUG

pacritinib in combination with talazoparib

Also known as: talzenna

Dose Level -1; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

pacritinib DRUG

pacritinib in combination with talazoparib

Also known as: vonjo

Dose Level -1; Dose Level 1; Dose Level 2; Dose Level 3; Dose Level 4

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically or cytologically confirmed primary myelofibrosis (PMF), post-polycythemia vera-myelofibrosis (PPV-MF), post-essential thrombocythemia-myelofibrosis (PET-MF), chronic myelomonocytic leukemia, polycythemia vera, or essential thrombocytosis according to the 2008 World Health Organization criteria
• Subject has at least 2 symptoms with a score ≥ 3 or a total score of ≥ 12, as measured by the MFSAF(Myelofibrosis Symptom Assessment Form) v4.0
• Subject classified as intermediate-2 or high-risk MF, as defined by the Dynamic International Prognostic Scoring System Plus (DIPSS+70).
• Age \> 18 years.
• ECOG (Eastern Cooperative Oncology Group) performance status 0-2
• Subject must have received prior treatment with a single JAK2 inhibitor 4.1.6 for at least 12 weeks with documented disease progression OR subject must have appearance of new splenomegaly that is palpable to at least 5 cm below the left costal margin (LCM) in subjects with no evidence of splenomegaly prior to the initiation of any first line JAK2 inhibitor
• Baseline QTc (corrected QT interval) \<0.47 seconds (Bazett formula)
• Patients must have normal organ function as defined in protocol.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document

You may not qualify if:

• Patients may not be receiving any other investigational agents
• Subjects must not be experiencing toxicity due to prior therapy that has not resolved to ≤Grade 1 by study registration, with the exception of sensory neuropathy related to previous systemic therapy exposure, alopecia and fatigue.
• Patients that have transformed to Acute Myeloid Leukemia defined by \>20% blasts count on peripheral blood smear or bone marrow biopsy evaluation
• Uncontrolled inter-current illness including, but not limited to, any other malignancy (with the exception of hormonal therapy for breast cancer/prostate cancer in remission \>1 year and for non-hormonal therapies for other cancers in remission for \>3 years), other ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patients with history of hemorrhagic stroke and evidence of uncontrolled bleeding as well as bleeding disorder
• Known HIV positive patients on combination antiretroviral therapy are ineligible because these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Pregnant or breast-feeding.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

RECRUITING

MeSH Terms

Conditions

Primary Myelofibrosis; Leukemia, Myelomonocytic, Chronic; Polycythemia Vera; Thrombocythemia, Essential; Myeloproliferative Disorders

Interventions

talazoparib; 11-(2-pyrrolidin-1-ylethoxy)-14,19-dioxa-5,7,26-triazatetracyclo(19.3.1.1(2,6).1(8,12))heptacosa-1(25),2(26),3,5,8,10,12(27),16,21,23-decaene

Condition Hierarchy (Ancestors)

Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Leukemia, Myeloid; Leukemia; Neoplasms by Histologic Type; Neoplasms; Myelodysplastic-Myeloproliferative Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Blood Coagulation Disorders; Thrombocytosis; Blood Platelet Disorders; Hemorrhagic Disorders

Study Officials

• Peter Abdelmessieh, DO, MSc

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Abigail Protocol Development Coordinator

CONTACT

215-728-2451; abigail.okeefe@fccc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 12, 2024
• First Posted: January 23, 2024
• Study Start: April 5, 2024
• Primary Completion (Estimated): August 22, 2029
• Study Completion (Estimated): August 27, 2030
• Last Updated: May 3, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)