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MyelofibrosisPhase 1/2NCT04354727

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

A Phase 1/2 study testing APG-1252 and Ruxolitinib in people with Myelofibrosis, run by Ascentage Pharma Group Inc. at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Myelofibrosis
What is being tested?
APG-1252 and Ruxolitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
15 Dec 2020to 15 Jun 2023
Phase
Phase 1/2
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

  • 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
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  • 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:
  • Direct bilirubin < 2.0 mg/dL (unless Gilbert's syndrome and evidence of hemolysis)
  • Serum creatinine < 1.5 mg/dL, if >1.5 mg/dL, creatinine clearance must be ≥ 50 mL/min
  • Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 3 x upper limit of normal (unless considered to be related to myelofibrosis or patient has known history of Gilberts)
  • Alkaline phosphatase < 2.5 x ULN
  • Albumin ≥ 2.5g/dl
  • Willingness to use contraception method that is deemed effective by the investigator by female patients of child bearing potential (postmenopausal women amenorrhea for at least 12 months to be considered of non-childbearing potential) and males with partners of child bearing potential, throughout the treatment period and for at least three months following the last dose of study drug
  • Ability to understand and willingness to sign a written informed consent form
  • Willingness and ability to comply with study procedures and follow-up examination

Who cannot join

  • 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
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  • 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
  • Family history of long QT syndrome or corrected QT interval (QTc) (Fridericia or Bazett) > 480 msec
  • Active infection requiring systemic antibiotic/ antifungal medication, known clinically active hepatitis B or C infection, or on antiretroviral therapy for HIV disease
  • Uncontrolled concurrent illness including, but not limited to: psychiatric illness/social situations that would limit compliance with the study requirements or any other condition or circumstance that would, in the opinion of the investigator, make the patient unsuitable for participation in the study
  • Women who are pregnant, breast feeding or women of child-bearing potential (WOCBP) not using an effective method of birth control. WOCBP are sexually active mature women who have not undergone a hysterectomy or who have not been achieved post-menopause for at least 12 consecutive months. WOCBP must have a negative serum pregnancy test with 72 hours of receiving the first dose of study medication
  • Male patients whose sexual partners are WOCBP not using effective birth control

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Banner MD Anderson Cancer Center

    Gilbert, Arizona, 85234

  • University of Texas MD Anderson Cancer Center

    Houston, Texas, 77030

Other trials in United States

About this study

Official title: Phase Ib/II Study of APG-1252 in Patients With Myelofibrosis Who Progressed After Initial Therapy

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.

Read the detailed description

Part 1 will evaluate safety of APG-1252 monotherapy using a 3+3 dose escalation study design. The starting dose of APG-1252 monotherapy will be 160 mg administered as an intravenous injection over 30 minutes once weekly in a 28-day cycle. If the APG-1252 at 160 mg is tolerated (0/3 and ≤ 1/6 DLTs), dose escalation to 240 mg will be evaluated and declared as recommended phase 2 dose (RP2D) if tolerated. No doses higher than 240 mg once per week will be explored. If the 160 mg once weekly dose schedule is not tolerated (≥ 2/3 or ≥ 2/6 DLTs) de-escalation to 80 mg once weekly dose will be explored. No doses under 80 mg of APG-1252 will be explored as monotherapy. Maximum tolerated dose (MTD)/RP2D is defined as the highest dose with ≤ 1/6 patients with dose limiting toxicities. A maximum of 6 patients will be treated at the APG-1252 monotherapy dose level to further characterize safety. Part 2 will commence once APG-1252 monotherapy MTD/RP2D is determined following review of safety and tolerability of APG-1252 monotherapy and discussion between sponsor and investigators. In Part 2, APG-1252 will be tested in combination with ruxolitinib. Part 2 will evaluate tolerability and clinical benefit of the combination APG-1252 plus ruxolitinib using a 3+3 dose escalation design. Patients starting APG-1252 treatment as an addition to ruxolitinib should have been on ruxolitinib daily dose for at least 5 days at the same dose. If they were on fedratinib they should discontinue fedratinib and switch to ruxolitinib for at least 5 days before the addition of APG-1252. The starting dose of APG-1252 in Part 2, will be one dose level lower than the MTD of APG-1252 as monotherapy (i.e, at 80 mg if MTD is 160 and 160 mg if MTD is 240 mg) and will be increased to a maximum of 240 mg once per week, added to ruxolitinib. Once the MTD/RP2D of combination arm is determined, additional patients up to a maximum of 15 will be treated at the RP2D to further evaluate safety and clinical benefit.

Conditions
Myelofibrosis
Being tested
APG-1252, Ruxolitinib
Keywords
JAK2 wild type, JAK2V617F mutation, Thrombocythemia, Polycythemia vera
Medical subject headings
Primary Myelofibrosis, Thrombocytosis, Polycythemia Vera

What participants receive

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

  • APG-1252Drug

    infusion once weekly

  • RuxolitinibDrug

    Also called Jakafi

    taken orally twice a day

Study groups in NCT04354727
Study groupRoleWhat they receive
APG-1252ExperimentalNot described
Receives: Drug: APG-1252
APG-1252 + RuxolitinibExperimentalNot described
Receives: Drug: APG-1252; Drug: Ruxolitinib

What is being measured

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

  1. 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

    Measured: 28 days

  2. Spleen Volume Measurement Reduction

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

    Measured: 24 weeks

Timeline

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

  1. First posted21 Apr 2020
  2. Study start15 Dec 2020 (estimated)
  3. Primary completion15 Dec 2022 (estimated)
  4. Study completion15 Jun 2023 (estimated)

Why it stopped: Sponsor decision

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04354727
Sponsor's protocol ID
APG1252MU101
Status last verified
Jul 2022
First submitted
17 Apr 2020
Last updated
12 Jul 2022
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing APG-1252 and Ruxolitinib in people with Myelofibrosis, run by Ascentage Pharma Group Inc. at 2 sites 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 23 inclusion and 20 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 12 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites 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 combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

Dose-limiting toxicity (DLT) rate at each dose level (time frame: 28 days). The study lists 2 primary outcomes in all. 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 NCT04354727.

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 12 Jul 2022.

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