Hepatomegaly, Myelofibrosis Transformation in Essential Thrombocythemia, Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, Primary Myelofibrosis, Splenomegaly
Conditions
Brief summary
This phase II trial studies how well nivolumab works in treating patients with primary myelofibrosis, post-essential thrombocythemia myelofibrosis, or post-polycythemia vera myelofibrosis. Immunotherapy with monoclonal antibodies, such as nivolumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.
Detailed description
PRIMARY OBJECTIVES: I. To determine the efficacy/clinical activity of nivolumab in patients with myelofibrosis (MF). SECONDARY OBJECTIVES: I. To determine the safety of nivolumab in patients with MF. TERTIARY OBJECTIVES: I. To explore time to response and duration of response. II. To assess changes in symptom burden. III. To explore changes in bone marrow fibrosis. IV. To explore changes in Janus kinase 2 valine at amino acid position 617 (JAK2V617F) (or other molecular marker) allele burden or changes in cytogenetic abnormalities. OUTLINE: Patients receive nivolumab intravenously (IV) over 60 minutes once every 2 weeks for 8 doses and then once every 12 weeks thereafter. Treatment may continue for up to 4 years in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up at 30, 60, and 100 days.
Interventions
OTHERLaboratory Biomarker Analysis
Correlative studies
BIOLOGICALNivolumab
Given IV
OTHERQuality-of-Life Assessment
Ancillary studies
Sponsors
National Cancer Institute (NCI)
M.D. Anderson Cancer Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of MF (either primary or post essential thrombocythemia/polycythemia vera) requiring therapy, including those previously treated and relapsed or refractory, or if newly diagnosed, with intermediate-1 or -2 or high risk according to International Prognostic Scoring System (IPSS) * Previously treated with ruxolitinib (unless not a good candidate for ruxolitinib therapy in the judgment of treating physician) * Palpable splenomegaly or hepatomegaly of more than or equal to 5 cm below left or right, respectively, costal margin on physical exam * Understanding and voluntary signing an institutional review board (IRB)-approved informed consent form * No prior history of immune checkpoint modulator therapy * Disease-free of other malignancies * Eastern Cooperative Oncology Group (ECOG) performance status 0 to 2 * Negative pregnancy test in females of childbearing potential (FCBP); male patients with female partners of child-bearing potential and female patients of childbearing potential are required to use two forms of acceptable contraception, including one barrier method, during their participation in the study and for 23 weeks (for females) or 31 weeks (for males) following the last dose of study medication; acceptable forms of contraception include 1 highly effective method such as an intrauterine device (IUD), hormonal (birth control pills, injections, or implants), tubal ligation, or partner's vasectomy and at least 1 additional approved barrier method such as a latex condom, diaphragm, or cervical cap plus spermicide; female patients of childbearing potential must not be breast-feeding or planning to breast feed and must have a negative pregnancy test within 24 hours of the first study treatment * Direct bilirubin equal to or less than 1.5 x upper limit of normal (ULN) * Serum creatinine equal to or less than 1.5 x ULN * Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) equal to or less than 2.5 x ULN (unless considered to be related to MF or patient has known history of Gilberts, in which case it must be equal to or less than 5 x ULN)
Exclusion criteria
* Use of any other standard or experimental therapy within 14 days of starting study therapy * Lack of recovery from all toxicity from previous therapy to grade 1 or baseline * Any concurrent severe and/or uncontrolled medical conditions that could increase the patient's risk for toxicity while in the study or that could confound discrimination between disease- and study treatment-related toxicities * Documented history of a cerebral vascular event (stroke or transient ischemic attack), unstable angina, myocardial infarction, or cardiac symptoms consistent with New York Heart Association class III-IV within 6 months prior to their first dose of the study drugs * Patients who are currently receiving chronic (\> 14 days) treatment with corticosteroids at a dose equal to or more than 10 mg of prednisone (or its glucocorticoid equivalent) per day, or any other chronic immunosuppressive treatment that cannot be discontinued prior to starting study drug * Patients with autoimmune diseases are excluded: patients with a history of inflammatory bowel disease (including Crohn's disease and ulcerative colitis) are excluded from this study as are patients with a history of autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis \[scleroderma\], systemic lupus erythematosus, autoimmune vasculitis) * Pregnant or breast feeding (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive beta-human chorionic gonadotropin (HCG) laboratory test * Known positive for human immunodeficiency virus (HIV) or infectious hepatitis, type A, B or C * The use of dietary supplements or herbal medications within 7 days of starting study therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate, Defined as Complete Remission + Partial Remission + Clinical Improvement | 14 weeks (after 8 doses of therapy) | Responses will be categorized according to the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukmiaNet consensus criteria for myelofibrosis. |
Countries
United States
Participant flow
Recruitment details
Recruitment Period: May 2015 to October 2017
Participants by arm
| Arm | Count |
|---|---|
| Treatment (Nivolumab) Patients receive nivolumab IV over 60 minutes once every 2 weeks for 8 doses and then once every 12 weeks thereafter. Treatment may continue for up to 4 years in the absence of disease progression or unacceptable toxicity.
Laboratory Biomarker Analysis: Correlative studies
Nivolumab: Given IV
Quality-of-Life Assessment: Ancillary studies | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Treatment (Nivolumab) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 8 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 74 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 8 Participants |
| Region of Enrollment United States | 8 Participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 3 / 8 |
| other Total, other adverse events | 7 / 8 |
| serious Total, serious adverse events | 6 / 8 |
Outcome results
Primary
Objective Response Rate, Defined as Complete Remission + Partial Remission + Clinical Improvement
Responses will be categorized according to the revised International Working Group-Myeloproliferative Neoplasms Research and Treatment and European LeukmiaNet consensus criteria for myelofibrosis.
Time frame: 14 weeks (after 8 doses of therapy)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Treatment (Nivolumab) | Objective Response Rate, Defined as Complete Remission + Partial Remission + Clinical Improvement | 0 Participants |