PD-1 Inhibition in Advanced Myeloproliferative Neoplasms

NCT03065400 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: GCO 16-2350
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 3

Brief 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). 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. 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.

Conditions

Chronic Phase Myelofibrosis; Primary Myelofibrosis; Post-essential Thrombocythemia Myelofibrosis; Polycythemia Vera

Keywords

Myelofibrosis; Acute Leukemia

Outcome Measures

Primary Outcomes (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

  18 weeks

Secondary Outcomes (1)

• Acute Myeloid Leukemia Response Criteria

  18 weeks

Study Arms (1)

Pembolizumab

EXPERIMENTAL

Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

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

Also known as: Keytruda

Pembolizumab

Eligibility Criteria

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

You may qualify if:

• 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)
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• John Mascarenhas: lead
• Massachusetts General Hospital: collaborator
• Montefiore Medical Center: collaborator

Study Sites (3)

Harvard Medical School Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Montefiore Medical Center Division of Hematology, Department of Oncology

The Bronx, New York, 10467, United States

Location

Related Publications (1)

• 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.

  PMID: 34581778 DERIVED

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Mikaela Dougherty
• Organization: Icahn School of Medicine at Mount Sinai

Mikaela.dougherty@mssm.edu

212-241-8839

Study Officials

• John Mascarenhas, MD

  Icahn School of Medicine at Mount Sinai

  STUDY CHAIR

• Gabriela Hobbs, MD

  Harvard Medical School Massachussets General Hospital

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 22, 2017
• First Posted: February 27, 2017
• Study Start: June 14, 2017
• Primary Completion: May 28, 2020
• Study Completion: May 28, 2020
• Last Updated: June 21, 2021
• Results First Posted: June 21, 2021

Record last verified: 2021-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)