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NCT03065400

PD-1 Inhibition in Advanced Myeloproliferative Neoplasms

Completed Phase 2 Results posted Last updated 21 June 2021
What this trial tests

Phase 2 trial testing Pembrolizumab in Chronic Phase Myelofibrosis in 10 participants. Completed in 28 May 2020.

Timeline
14 June 2017
Primary endpoint
28 May 2020
28 May 2020

Quick facts

Lead sponsorJohn Mascarenhas
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment10
Start date14 June 2017
Primary completion28 May 2020
Estimated completion28 May 2020
Sites3 locations across United States

Drugs / interventions tested

Conditions studied

Sponsor

John Mascarenhas — full company profile →

Who can join

18 and older, any sex, with Chronic Phase Myelofibrosis or Primary Myelofibrosis. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

European Leukemia Net -International Working Group (ELN-IWG) Criteria Primary · 18 weeks

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 Re

GroupValue95% CI
Pembolizumab0
Acute Myeloid Leukemia Response Criteria Secondary · 18 weeks

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

GroupValue95% CI
Pembolizumab0

Adverse events — posted to ClinicalTrials.gov

Time frame: 18 weeks. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Pembolizumab
Serious: 3/10 (30%)
Deaths: 1/10

Serious adverse events (5 terms)

ReactionSystemPembolizumab
WeaknessNervous system disorders
PneumoniaRespiratory, thoracic and mediastinal disorders
Supraventricular TachycardiaCardiac disorders
High grade pleomorphic sarcoma of left breast.Reproductive system and breast disorders
Respiraitory FailureRespiratory, thoracic and mediastinal disorders
Other adverse events (30 terms — click to expand)

ReactionSystemPembolizumab
AnemiaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
LymphopeniaBlood and lymphatic system disorders
HyperglycemiaEndocrine disorders
CoughRespiratory, thoracic and mediastinal disorders
FatigueGeneral disorders
DyspneaRespiratory, thoracic and mediastinal disorders
LeukopeniaBlood and lymphatic system disorders
WBC DecreeasedBlood and lymphatic system disorders
HyperuricemiaRenal and urinary disorders
HeadacheNervous system disorders
AST IncreasedHepatobiliary disorders
HypoalbuminemiaHepatobiliary disorders
Chest PainRespiratory, thoracic and mediastinal disorders
DiarrheaGastrointestinal disorders
DizzinessNervous system disorders
FeverGeneral disorders
NauseaGastrointestinal disorders
WeaknessNervous system disorders
ALP IncreasedHepatobiliary disorders
HypocalcaemiaRenal and urinary disorders
HypernatremiaRenal and urinary disorders
Blurred VisionNervous system disorders
ConstipationGastrointestinal disorders
DyspepsiaGastrointestinal disorders
Productive CoughRespiratory, thoracic and mediastinal disorders
RashSkin and subcutaneous tissue disorders
Sore ThroatRespiratory, thoracic and mediastinal disorders
Upper Respiratory InfectionRespiratory, thoracic and mediastinal disorders
Weight LossGeneral disorders

Most-reported serious reactions: Weakness, Pneumonia, Supraventricular Tachycardia, High grade pleomorphic sarcoma of left breast., Respiraitory Failure.

Data from ClinicalTrials.gov NCT03065400 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Molecular pathogenesis of the myeloproliferative neoplasms.
    Greenfield G, McMullin MF, Mills K. · · 2021 · cited 83× · PMID 34193229 · DOI 10.1186/s13045-021-01116-z
  2. Management of myelofibrosis after ruxolitinib failure.
    Harrison CN, Schaap N, Mesa RA. · · 2020 · cited 70× · PMID 32198525 · DOI 10.1007/s00277-020-04002-9
  3. Novel therapeutics in myeloproliferative neoplasms.
    Venugopal S, Mascarenhas J. · · 2020 · cited 32× · PMID 33267911 · DOI 10.1186/s13045-020-00995-y
  4. PD-1 inhibition in advanced myeloproliferative neoplasms.
    Hobbs G, Cimen Bozkus C, Moshier E, Dougherty M, et al · · 2021 · cited 30× · PMID 34581778 · DOI 10.1182/bloodadvances.2021005491
  5. Inflammatory Microenvironment and Specific T Cells in Myeloproliferative Neoplasms: Immunopathogenesis and Novel Immunotherapies.
    Nasillo V, Riva G, Paolini A, Forghieri F, et al · · 2021 · cited 28× · PMID 33672997 · DOI 10.3390/ijms22041906
  6. Challenges and Perspectives for Therapeutic Targeting of Myeloproliferative Neoplasms.
    Brkic S, Meyer SC. · · 2021 · cited 26× · PMID 33403355 · DOI 10.1097/hs9.0000000000000516
  7. Cancer Immune Therapy for Philadelphia Chromosome-Negative Chronic Myeloproliferative Neoplasms.
    Holmström MO, Hasselbalch HC, Andersen MH. · · 2020 · cited 22× · PMID 32630667 · DOI 10.3390/cancers12071763
  8. Management of challenging myelofibrosis after JAK inhibitor failure and/or progression.
    Scherber RM, Mesa RA. · · 2020 · cited 19× · PMID 32593470 · DOI 10.1016/j.blre.2020.100716

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