PD-1 Inhibition in Advanced Myeloproliferative Neoplasms
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|ClinicalTrials.gov Identifier: NCT03065400|
Recruitment Status : Completed
First Posted : February 27, 2017
Results First Posted : June 21, 2021
Last Update Posted : June 21, 2021
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Phase Myelofibrosis Primary Myelofibrosis Post-essential Thrombocythemia Myelofibrosis Polycythemia Vera||Drug: Pembrolizumab||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||10 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||PD-1 Inhibition in Advanced Myeloproliferative Neoplasms|
|Actual Study Start Date :||June 14, 2017|
|Actual Primary Completion Date :||May 28, 2020|
|Actual Study Completion Date :||May 28, 2020|
200 mg of Pembolizumab administered via intravenous infusion over 30 mins given every 3 weeks
Other Name: Keytruda
- European Leukemia Net -International Working Group (ELN-IWG) Criteria [ Time Frame: 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 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
- Acute Myeloid Leukemia Response Criteria [ Time Frame: 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 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03065400
|United States, Massachusetts|
|Harvard Medical School Massachusetts General Hospital|
|Boston, Massachusetts, United States, 02114|
|United States, New York|
|Montefiore Medical Center Division of Hematology, Department of Oncology|
|Bronx, New York, United States, 10467|
|Icahn School of Medicine at Mount Sinai|
|New York, New York, United States, 10029|
|Study Chair:||John Mascarenhas, MD||Icahn School of Medicine at Mount Sinai|
|Study Chair:||Gabriela Hobbs, MD||Harvard Medical School Massachussets General Hospital|