A Study of APG-1252 in Patients With Myelofibrosis Who Progressed After Initial Therapy

NCT04354727 | Withdrawn Phase 1 FDA Drug

• 1 other identifier: APG1252MU101
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

The study is a designed to evaluate safety and activity of APG-1252 when administered as monotherapy and in combination with ruxolitinib in previously ruxolitinib treated myelofibrosis patients.

Conditions

Myelofibrosis

Keywords

JAK2 wild type; JAK2V617F mutation; Thrombocythemia; Polycythemia vera

Outcome Measures

Primary Outcomes (2)

• Dose-limiting toxicity (DLT) rate at each dose level

  DLT will be assessed within the first 28-day cycle of study treatment via CTCAE version 5.0

  28 days

• Spleen Volume Measurement Reduction

  At least a 35% reduction in spleen volume or ≥ 50% reduction in myelofibrosis related total symptom score (TSS)

  24 weeks

Study Arms (2)

APG-1252

EXPERIMENTAL

Drug: APG-1252

APG-1252 + Ruxolitinib

EXPERIMENTAL

Drug: APG-1252; Drug: Ruxolitinib

Interventions

APG-1252 DRUG

infusion once weekly

APG-1252; APG-1252 + Ruxolitinib

Ruxolitinib DRUG

taken orally twice a day

Also known as: Jakafi

APG-1252 + Ruxolitinib

Eligibility Criteria

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

You may qualify if:

• Histologically or cytologically confirmed myelofibrosis requiring therapy including:
• Either primary or post essential thrombocythemia/polycythemia vera
• Have intermediate-2 or high-risk myelofibrosis by International Prognostic Scoring System (IPSS) scoring system
• If intermediate-1 myelofibrosis must have palpable splenomegaly ≥ 5 cm below left costal margin
• Either in chronic (CP) or accelerated phase (AP)
• Patients can be either JAK2 wild type or JAK2V617F mutated
• Patients must be ineligible or unwilling to undergo a stem cell transplantation or receive any other approved standard of care at the time of study entry
• Patients have been previously treated with a JAK inhibitor (JAKi) and are intolerant, resistant, refractory or lost response to the JAKi ruxolitinib or fedratinib, or had sub-optimal response to ruxolitinib. Patients in Part 1 will be those ineligible to receive ruxolitinib and other approved standard of care. (Patients will be defined as having received sub-optimal response to ruxolitinib if, they achieved inadequate response to ruxolitinib based therapy after 6 months of treatment, or had been on a stable dose of ruxolitinib based therapy for \< 24 weeks and had shown initial response but in opinion of investigators were unlikely to benefit from continuing dose and schedule of ruxolitinib).
• Eastern Cooperative Oncology Group (ECOG) performance score of 0-2
• Adequate bone marrow function:
• Absolute neutrophil count (ANC) ≥ 0.750 X 10˄9/L
• Hemoglobin (Hb) ≥ 9.0 g/dL
• Platelets count ≥ 50 X 10˄9/L (independent of transfusion within14 days of first dose)
• International normalized ratio (INR), prothrombin time (PT) or activated partial thromboplastin time (aPTT) ≤1.5 X upper limit of normal (ULN) unless the subject is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants
• Adequate renal and liver function as indicated by:

You may not qualify if:

• Received standard or experimental therapy within 14 days or 5 half-lives (whichever is greater) before starting study therapy
• Previously received other B-cell lymphoma-extra large (Bcl-xL) inhibitors
• Receiving concomitant anticancer therapy, except hormonal therapy and patients on ruxolitinib
• Disease associated with myelofibrosis such as metastatic carcinoma, lymphoma, myelodysplasia, hairy cell leukemia, mast cell disease or acute leukemia
• Radiation within 14 days of study entry, thoracic radiation within 28 days of study entry
• Has gastrointestinal conditions that could affect the absorption of oral medication
• Has known active central nervous system (CNS) involvements
• Lack of toxicity recovery from previous therapy ≤ grade 1 or baseline (except alopecia, hemoglobin, neutropenia and thrombocytopenia)
• Use of therapeutic anticoagulants
• Failure to recover adequately, as judged by the investigator, from prior surgical procedures. Patients with active wound healing, patients who have had major surgery within 28 days from study entry, and patients who have had minor surgery within 14 days of study entry
• Unstable angina, or other significant cardiac condition including:
• Unstable arrhythmia on treatment including permanent cardiac pacemaker
• History of symptomatic congestive heart failure (New York Heart Association \[NYHA\] Class III or IV)
• History of myocardial infarction within 6 months of enrollment
• Current unstable angina

Sponsors & Collaborators

• Ascentage Pharma Group Inc.: lead

Study Sites (2)

Banner MD Anderson Cancer Center

Gilbert, Arizona, 85234, United States

Location

University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

MeSH Terms

Conditions

Primary Myelofibrosis; Thrombocytosis; Polycythemia Vera

Interventions

pelcitoclax; ruxolitinib

Condition Hierarchy (Ancestors)

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

Study Officials

• Yifan Zhai, MD, PhD

  Ascentage Pharma Group Inc.

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: April 17, 2020
• First Posted: April 21, 2020
• Study Start: December 15, 2020
• Primary Completion: December 15, 2022
• Study Completion: June 15, 2023
• Last Updated: July 12, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)