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Chronic Phase MyelofibrosisPhase 2NCT03065400

PD-1 Inhibition in Advanced Myeloproliferative Neoplasms

A Phase 2 study testing Pembrolizumab in people with Chronic Phase Myelofibrosis and Primary Myelofibrosis, run by John Mascarenhas at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The purpose of this study is to test the effectiveness of a drug called pembrolizumab in patients with Myeloproliferative Neoplasm (MPN); chronic phase (MF-CP), accelerated phase (MPN-AP), or blast phase (MF-BP). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
3 sitesUnited States
Study dates
14 Jun 2017to 28 May 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

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

  • Be willing and able to provide written informed consent/assent for the trial.
  • Be ≥ 18 years of age on day of signing consent.
  • Must have a diagnosis of chronic phase (CP) (defined as peripheral blood and bone marrow <10% blasts) primary myelofibrosis (PMF) or post essential thrombocythemia (post-ET) or polycythemia vera (post-PV) myelofibrosis by World Health Organization (WHO) criteria OR a diagnosis of a myeloproliferative neoplasm in accelerated/blast phase (MPN-AP/BP) defined as either a peripheral blood or bone marrow with =10% blasts .
  • If the diagnosis is MF-CP, must have Dynamic International Prognostic Scoring System (DIPSS) intermediate-2/high risk disease and either be intolerant/resistant to ruxolitinib as determined by the treating investigator or ineligible for ruxolitinib therapy as determined by the treating investigator .
  • If the diagnosis is MPN-AP/BP, must have progressive/resistant disease after treatment with a DNMT1 inhibitor therapy (azacytidine, decitabine) as determined by the treating investigator .
  • Either not eligible or unwilling to proceed with hematopoietic stem cell transplantation (HSCT)
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  • Have a performance status of 0 or 1 on the ECOG Performance Scale.
  • Demonstrate adequate organ function as defined in Table 1, all screening labs should be performed within 10 days of treatment initiation.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication (Reference Section 5.7.2). Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.

Who cannot join

  • Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
  • Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or sponsor staff directly involved with this trial, unless prospective IRB approval (by chair or designee) is given allowing exception to this criterion for a specific subject.
  • Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
  • Has a known history of active TB (Bacillus Tuberculosis)
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
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  • Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events due to a previously administered agent.
  • Note: Subjects with = Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
  • Note: If subject received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
  • Has a known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
  • Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • Has known history of, or any evidence of active, non-infectious pneumonitis.
  • Has an active infection requiring systemic therapy.
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
  • Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment.
  • Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent. "Anti-CD137 or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways)
  • Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
  • Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
  • Has received a live vaccine within 30 days of planned start of study therapy. Note: Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Harvard Medical School Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Icahn School of Medicine at Mount Sinai

    New York, New York, 10029

  • Montefiore Medical Center Division of Hematology, Department of Oncology

    The Bronx, New York, 10467

Other trials in United States

About this study

The purpose of this study is to test the effectiveness of a drug called pembrolizumab in patients with Myeloproliferative Neoplasm (MPN); chronic phase (MF-CP), accelerated phase (MPN-AP), or blast phase (MF-BP). Myelofibrosis neoplasm (MPN) is a group of diseases of the bone marrow in which excessive cells are produced.

Pembrolizumab also known as Keytruda is a drug that has recently been approved in the United Stated by the Food and Drug Administration (FDA) for the treatment of patients with unresectable or metastatic melanoma and disease progression. Pembrolizumab is experimental in the treatment of MPN. The researchers want to find out what effects, good and /or bad it has on participants and the disease.

Read more

Participants qualify to take part in this research study if have been diagnosed with a MPN blood disorder called myelofibrosis (MF). Accelerated (10-19% blasts in the blood or bone marrow) and blast phase (>20% blasts in the blood or bone marrow) MPN has been a difficult disease to treat. The term "blasts" refers to immature cells found in the bone marrow. They are not fully developed, and therefore, do not yet carry out any particular function within the body.

Funds for conducting this research are provided by Merck and Company, the manufacturer of the study drug pembrolizumab.

Read the detailed description

The researchers propose a Simon-two stage design for this study. The researchers will test pembrolizumab at the FDA approved dose (in head and neck cancer) of 200mg dose administered via intravenous infusion over 30 minutes given every 3 weeks. Nine patients will be enrolled in the first stage of the Simon-two stage design, and 15 in the second stage. A treatment cycle is 3 weeks and the core study period is 6 cycles. Response assessment by established consensus criteria will be used to assess response after 6 cycles in order to determine if the trial will progress to the second stage and for the purpose of determining the primary endpoint. In addition, allowed will be a maximum of ten patients with accelerated or blast phase disease (MPN-AP/BP) who are refractory or intolerant to conventional therapies such as decitabine, and in which hematopoietic stem cell transplant is not a therapeutic option (exploratory cohort), to enroll in the study as a separate exploratory cohort. These patients can be enrolled during stage 1 or 2 and will be analyzed separately from the primary cohort population.

Exploratory biomarkers will be obtained from enrolled patients at baseline, cycle 3 and cycle 7 and at 1 year of therapy. Patients that obtain at least a clinical improvement after 6 cycles of therapy can continue receiving pembrolizumab until evidence of disease progression, unacceptable toxicity, and patient or physician decision for a maximum of 2 years.

Being tested
Pembrolizumab
Keywords
Myelofibrosis, Acute Leukemia
Medical subject headings
Primary Myelofibrosis, Polycythemia Vera

What participants receive

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

  • PembrolizumabDrug

    Also called Keytruda

    200 mg of Pembolizumab administered via intravenous infusion over 30 mins given every 3 weeks

Study groups in NCT03065400
Study groupRoleWhat they receive
PembolizumabExperimentalNot described
Receives: Drug: Pembrolizumab

What is being measured

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

  1. European Leukemia Net -International Working Group (ELN-IWG) Criteria

    The proportion of treated MF-CP patients (primary cohort) that achieve at least a clinical improvement (CI, PR, CR) by combined European Leukemia Net -International Working Group (ELN-IWG) criteria after 6 cycles of pembrolizumab therapy.

    Complete Remission - CR: Bone marrow: Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF and Peripheral blood: Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥ 1 × 109/L and <UNL; Platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH Partial Remission (PR): Hemoglobin ≥100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; platelet count ≥100 × 109/L and <UNL; <2% immature myeloid cells and Clinical: Resolution of disease symptoms; spleen and liver not palpable; no evidence of EMH or Bone marrow: Age-adjusted normocellularity; <5% blasts; ≤grade 1 MF, and Hemoglobin ≥85 but <100 g/L and <UNL; neutrophil count ≥1 × 109/L and <UNL; plat

    Measured: 18 weeks

Secondary outcomes (1)

  1. Acute Myeloid Leukemia Response Criteria

    The proportion of treated MPN-AP/BP patients (exploratory cohort) that achieve at least a complete morphologic remission of the leukemic blasts (CR, Cri) by Acute Myeloid Leukemia Response Criteria within 6 cycles of pembrolizumab therapy.

    Acute Myeloid Leukemia Response Assessment Criteria:

    Complete Response (CR) - The subject must be free of all symptoms related to leukemia and have an absolute neutrophil count of greater than 1 x 109/L, no need for red blood cell transfusion, platelet count greater than 100x 109/L, and normal marrow differential (<5% blasts) in a normo- or hypercellular marrow Complete Remission with Incomplete Hematologic Recovery (Cri) - As per CR but incomplete count recovery Partial Response - CR with 6-25% abnormal cells in the marrow or 50% decrease in bone marrow blasts

    Measured: 18 weeks

Timeline

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

  1. First posted27 Feb 2017
  2. Study start14 Jun 2017
  3. Primary completion28 May 2020
  4. Study completion28 May 2020

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03065400
Sponsor's protocol ID
GCO 16-2350
Status last verified
May 2021
First submitted
22 Feb 2017
Last updated
21 Jun 2021
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Hobbs G, Cimen Bozkus C, Moshier E, Dougherty M, Bar-Natan M, Sandy L, Johnson K, Foster JE, Som T, Macrae M, Marble H, Salama M, El Jamal SM, Zubizarreta N, Wadleigh M, Stone R, Bhardwaj N, Iancu-Rubin C, Mascarenhas J. PD-1 inhibition in advanced myeloproliferative neoplasms. Blood Adv. 2021 Dec 14;5(23):5086-5097. doi: 10.1182/bloodadvances.2021005491.

    PubMed 34581778

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Pembrolizumab in people with Chronic Phase Myelofibrosis and Primary Myelofibrosis, run by John Mascarenhas at 3 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 11 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: finished, as of the sponsor's last update on 21 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 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 phase mean?

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?

Yes. Results are posted in the registry (first posted 21 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

European Leukemia Net -International Working Group (ELN-IWG) Criteria (time frame: 18 weeks). 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 NCT03065400, which also lists 1 linked publication.

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 21 Jun 2021.

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