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Chronic Myelomonocytic LeukemiaPhase 1NCT02564536

Pacritinib in Combination With Low Dose Decitabine in Intermediate-High Risk Myelofibrosis or Myeloproliferative Neoplasm (MPN)/Myelodysplastic Syndrome (MDS)

A Phase 1 study testing Pacritinib and Decitabine in people with Chronic Myelomonocytic Leukemia and Juvenile Myelomonocytic Leukemia, run by Washington University School of Medicine.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

For the first 28 day cycle, all patients will be treated with single agent pacritinib at 200 mg twice daily. The investigators chose this starting dose based on the previous three phase I studies of pacritinib as a single agent which showed that the maximum tolerated dose (MTD) to be 500 mg, and subsequently, the dose… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pacritinib and Decitabine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
No sites listed yet
Study dates
Jun 2017to 30 Jun 2020
Phase
Phase 1
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

  • Confirmed diagnosis of:
  • Primary MF or post-PV/ET MF classified as high risk, intermediate-2 risk, or intermediate-1 risk who are unresponsive or unable to receive current therapy which may or may not include ruxolitinib OR
  • MPN/MDS Syndrome (chronic myelomonocytic leukemia [CMML], juvenile myelomonocytic leukemia [JMML], atypical chronic myeloid leukemia [aCML], or MDS/MPN unclassifiable)
  • ECOG 0-3
  • Required laboratory values:
  • Neutrophil count of ≥ 0.5 x 109/L
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  • Bone marrow blood blast count < 20%
  • AST and ALT ≤ 3 x ULN (≤ 5 x ULN if liver is involved by extramedullary hematopoiesis as judged by the investigator or if related to iron chelator therapy that was started within the prior 60 days)
  • Total creatinine < 2.5mg/dL
  • Total bilirubin ≤ 2.0 x ULN
  • Age ≥ 18 years old at enrollment.
  • If female, must be:
  • postmenopausal for at least 1 year before the screening visit OR
  • surgically sterile OR
  • agreeable to practicing 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment.
  • Able to swallow pills.
  • If a sexually active heterosexual male, must be agreeable to practicing 2 effective methods of contraception prior to study entry, for the duration of study participation, and for 30 days after the last dose of study treatment.
  • Ability to understand and willingness to sign an IRB approved written informed consent document (or that of legally authorized representative, if applicable).

Who cannot join

  • Prior treatment with more than two JAK2 inhibitors or with pacritinib
  • Known positive status for human immunodeficiency virus (HIV)
  • Chronic, active, or acute viral hepatitis A, B, or C infection, or a hepatitis B or C carrier
  • Use of chemotherapy, biologic therapy, radiation therapy, erythropoietin or related erythropoiesis stimulating agents, or investigational therapy within 2 weeks of the first dose of study drug
  • History of allogeneic stem cell transplant or transplant eligible
  • Currently receiving any other investigational agents
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  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to pacritinib or other agents used in the study
  • Ongoing gastrointestinal medical condition such as Crohn's disease, inflammatory bowel disease, chronic diarrhea, or chronic constipation that could interfere with absorption of oral medication
  • Active bleeding that requires hospitalization during the screening period
  • Cardiovascular disease, including recent history of or currently clinically symptomatic and uncontrolled congestive heart failure, arrhythmia, angina, QTc prolongation or other QTc risk factors, myocardial infarction. Patients with CTCAE grade 2 cardiac arrhythmias may be considered for inclusion if the arrhythmias are stable, asymptomatic, and unlikely to affect patient safety. Patients will e excluded if they have ongoing cardiac dysrhythmias of CTCAE grade ≥ 3, corrected QT interval (QTc) prolongation > 450 ms, or other factors that increase the risk for QT interval prolongation (e.g., heart failure, hypokalemia [defined as serum potassium < 3.0 mEq/L that is persistent and refractory to correction], or family history of long QT interval syndrome).
  • Other malignancy requiring active treatment at time of study entry
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, or serious medical or psychiatric illness/social situations that would limit compliance with study requirements.
  • Life expectancy < 6 months
  • Pregnant and/or breastfeeding. Patient must have a negative pregnancy test within 14 days of study entry.
  • Receiving treatment with any potent CYP3A4 inhibitors within 7 days of the first dose of study drug
  • Patients with MF who are eligible for enrollment in the pacritinib "PERSIST-2" study at WUSM (NCT02055781) HRPO 201406075.

About this study

Official title: A Pilot Study of Pacritinib in Combination With Low Dose Decitabine in Patients With Intermediate-High Risk Myelofibrosis or MPN/MDS Syndromes

For the first 28 day cycle, all patients will be treated with single agent pacritinib at 200 mg twice daily. The investigators chose this starting dose based on the previous three phase I studies of pacritinib as a single agent which showed that the maximum tolerated dose (MTD) to be 500 mg, and subsequently, the dose of 400 mg daily was recommended for the phase II studies.

Recently, the results of the phase III PERSIST-1 trial comparing pacritinib to best available therapy (BAT) in patients with MF was reported at the 2015 American Society of Clinical Oncology (ASCO) annual meeting. Pacritinib was found to be significantly more effective than BAT at reducing spleen volume at 24 weeks of therapy and improving constitutional symptoms.

Low dose decitabine has demonstrated depletion of DNMT1 in normal hematopoietic stem cells (HSC) without cytotoxicity and subcutaneous (SC) instead of intravenous (IV) administration may avoid high peak levels that can cause apoptosis. Furthermore, the low toxicity associated with low dose decitabine would allow for more frequent (1 to 3 times weekly) administration of the drug which would catch more cells in S-phase via greater exposure time. Based on these findings, a starting dose of decitabine 5 mg/m2 SC twice weekly should be well tolerated and effective in patients with MF and MPN/MDS syndromes when combined with pacritinib 400 mg daily.

Being tested
Pacritinib, Decitabine
Medical subject headings
Leukemia, Myelomonocytic, Chronic, Leukemia, Myelomonocytic, Juvenile, Leukemia, Myeloid, Chronic, Atypical, BCR-ABL Negative, Myeloproliferative Disorders, Myelodysplastic Syndromes, Primary Myelofibrosis

What participants receive

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

  • PacritinibDrug

    -Patients should take pacritinib at approximately the same times every day with a glass of water, with or without food.

  • DecitabineDrug

    -From commercial stock

Study groups in NCT02564536
Study groupRoleWhat they receive
Arm 1: Pacritinib and DecitabineExperimental* Patients will receive one cycle of single agent pacritinib. * Patients who tolerate single agent pacritinib will then receive up to 11 cycles of pacritinib and decitabine combination therapy. * Patients who do not tolerate single agent pacritinib (require dose interruption for more than 7 days before Cycle 2 Day 1) will be considered non-evaluable and replaced. * Pacritinib will be administered orally at a dose of 200 mg twice daily continuously for Days 1 through 28 of a 28-day cycle. * Decitabine will be administered as a subcutaneous injection in clinic on Days 1, 5, 8, 12, 15, 19, 22, and 26 of a 28-day cycle. * Patients may continue treatment for up to 12 cycles.
Receives: Drug: Pacritinib; Drug: Decitabine

What is being measured

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

  1. Safety of regimen as measured by adverse events

    The descriptions and grading for adverse events are found in the revised NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.0

    Measured: 30 days after completion of treatment (up to 1 year)

Secondary outcomes (4)

  1. Rate of objective response as defined by the International Working Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) consensus

    Objective response is defined as CR (complete remission/response) + PR (partial remission/response) + CI (clinical improvement).

    Measured: End of treatment (up to 48 weeks)

  2. Rate of hematologic response

    -Anemia response

    Anemia response is only applicable for patients with baseline hemoglobin level less than 10g/dL for 8 weeks or more and requires:

    *≥2 g/dL increase in hemoglobin level

    *becoming transfusion-independent (no RBC transfusions in past 1 month)

    -Platelet response

    Platelet response is only applicable for patients with a baseline platelet count of less than 50 x 10^9/L for 8 weeks or more, and requires:

    • 100% increase in platelet count AND
    • An absolute platelet count of at least 50 x 10^9/L

    Measured: End of treatment (up to 48 weeks)

  3. Rate of symptom response as measured by the total symptom score (TSS)

    A ≥50% reduction in the myeloproliferative neoplasm symptom assessment total symptom score

    Measured: End of treatment (up to 48 weeks)

  4. Rate of spleen response

    • A baseline splenomegaly that is palpable at 5-10 cm below the left costal margin becomes not palpable OR
    • A baseline splenomegaly that is palpable > 10 cm below the left costal margin decreases by ≥50% OR
    • A baseline splenomegaly that is palpable < 5 cm below the left costal margin is not eligible for spleen response OR
    • MRI or CT shows ≥35% spleen volume reduction

    Measured: End of treatment (up to 48 weeks)

Timeline

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

  1. First posted30 Sep 2015 (estimated)
  2. Study startJun 2017 (estimated)
  3. Primary completion30 Jun 2020 (estimated)
  4. Study completion30 Jun 2020 (estimated)

Why it stopped: Lack of funding following full FDA clinical hold

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
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
NCT02564536
Sponsor's protocol ID
201510166
Status last verified
May 2017
First submitted
29 Sep 2015
Last updated
8 May 2017
Results posted
No
Data monitoring committee
Yes
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 study testing Pacritinib and Decitabine in people with Chronic Myelomonocytic Leukemia and Juvenile Myelomonocytic Leukemia, run by Washington University School of Medicine.

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 18 inclusion and 16 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 8 May 2017. Status can change between updates, so confirm with the study contact before making plans.

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 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.

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?

Safety of regimen as measured by adverse events (time frame: 30 days after completion of treatment (up to 1 year)). 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 NCT02564536.

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 8 May 2017.

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