Nivolumab in Treating Patients With Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis

• Sponsor: M.D. Anderson Cancer Center (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02421354
• Collaborator: National Cancer Institute (NCI) (NIH)
• Enrollment: 8
• Location: 1
• Arm: 1
• Actual Duration (Months): 35
• Patients Per Site Per Month: 0.2

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatomegaly; Myelofibrosis Transformation in Essential Thrombocythemia; Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase; Primary Myelofibrosis; Splenomegaly	Other: Laboratory Biomarker Analysis; Biological: Nivolumab; Other: Quality-of-Life Assessment	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. To determine the efficacy/clinical activity of nivolumab in patients with myelofibrosis (MF).

SECONDARY OBJECTIVES:

1. To determine the safety of nivolumab in patients with MF.

TERTIARY OBJECTIVES:

1. 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 8 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 2 Study of Nivolumab in Patients With Primary Myelofibrosis, Post-Essential Thrombocythemia Myelofibrosis, or Post-Polycythemia Vera Myelofibrosis
• Actual Study Start Date: May 14, 2015
• Actual Primary Completion Date: Apr 13, 2018
• Actual Study Completion Date: Apr 13, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Nivolumab; Given IV; Other Names: BMS-936558 MDX-1106 NIVO ONO-4538 Opdivo ; Other: Quality-of-Life Assessment; Ancillary studies; Other Names: Quality of Life Assessment

Outcome Measures

Primary Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	M D Anderson Cancer Center	Houston	Texas	United States	77030

Sponsors and Collaborators

• M.D. Anderson Cancer Center
• National Cancer Institute (NCI)

Investigators

• Principal Investigator: Srdan Verstovsek, M.D. Anderson Cancer Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Aug 11, 2016

More Information

Additional Information:

• MD Anderson Cancer Center Website

Publications

None provided.

• Responsible Party: M.D. Anderson Cancer Center
• ClinicalTrials.gov Identifier: NCT02421354
• Other Study ID Numbers: 2014-0962; NCI-2015-00836; 2014-0962; P30CA016672
• First Posted: Apr 20, 2015
• Last Update Posted: May 15, 2019
• Last Verified: Apr 1, 2019

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Polycythemia Vera; Hepatomegaly; Primary Myelofibrosis; Polycythemia; Thrombocytosis; Thrombocythemia, Essential; Splenomegaly; Nivolumab

Study Results

Participant Flow

Recruitment Details	Recruitment Period: May 2015 to October 2017

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Period Title: Overall Study
STARTED	8
COMPLETED	8
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Overall Participants	8
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	0 0%
>=65 years	8 100%
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	74
Sex: Female, Male (Count of Participants)
Female	3 37.5%
Male	5 62.5%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	8 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	8 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response Rate, Defined as Complete Remission + Partial Remission + Clinical Improvement
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
Measure Participants	8
Count of Participants [Participants]	0 0%

Adverse Events

Time Frame	2 years, 5 months
Arm/Group Title	Treatment (Nivolumab)
Arm/Group Description	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
All Cause Mortality
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	3/8 (37.5%)
Serious Adverse Events
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	6/8 (75%)
Blood and lymphatic system disorders
Anemia	2/8 (25%)	2
Gastrointestinal disorders
Esophageal Varices Hemorrhage	1/8 (12.5%)	1
Gastric Hemorrhage	2/8 (25%)	4
General disorders
Abdominal Pain	1/8 (12.5%)	1
Back Pain	1/8 (12.5%)	1
Chest Pain	1/8 (12.5%)	1
Fever	1/8 (12.5%)	2
Headache	1/8 (12.5%)	1
Infections and infestations
Infection	1/8 (12.5%)	2
Urinary Tract Infection	1/8 (12.5%)	1
Injury, poisoning and procedural complications
Fall	1/8 (12.5%)	2
Nervous system disorders
Facial Nerve Disorder	1/8 (12.5%)	1
Renal and urinary disorders
Acute Kidney Injury	1/8 (12.5%)	2
Chronic Kidney Disease	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Pleural Effusion	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Urticaria	1/8 (12.5%)	1
Other (Not Including Serious) Adverse Events
	Treatment (Nivolumab)
	Affected / at Risk (%)	# Events
Total	7/8 (87.5%)
Blood and lymphatic system disorders
Leptomeningeal disease	1/8 (12.5%)	1
Anemia	1/8 (12.5%)	2
Neutropenia	1/8 (12.5%)	1
Thrombocytopenia	1/8 (12.5%)	1
Cardiac disorders
Cardiomegaly	1/8 (12.5%)	1
Ear and labyrinth disorders
Hemotympanum	1/8 (12.5%)	1
Gastrointestinal disorders
Mucositis	1/8 (12.5%)	1
Nausea	1/8 (12.5%)	1
Diarrhea	2/8 (25%)	3
Constipation	4/8 (50%)	4
Abdominal distention	1/8 (12.5%)	1
Esophageal Varicies	1/8 (12.5%)	1
General disorders
Pain	3/8 (37.5%)	5
Fever	1/8 (12.5%)	1
Edema	3/8 (37.5%)	3
Bruising	1/8 (12.5%)	1
Chills	1/8 (12.5%)	1
Hepatobiliary disorders
Hepatobiliary disorder	1/8 (12.5%)	1
Infections and infestations
Neutropenic Fever	1/8 (12.5%)	1
Infection	3/8 (37.5%)	4
Sinusitis	1/8 (12.5%)	1
Investigations
Increased Transaminases	1/8 (12.5%)	1
Hyperbilirubinemia	3/8 (37.5%)	3
Elevated Alkaline Phophatase	1/8 (12.5%)	1
Elevated Creatinine	1/8 (12.5%)	1
Metabolism and nutrition disorders
Hyperglycemia	1/8 (12.5%)	1
Hypoalbuminemia	1/8 (12.5%)	1
Hypokalemia	1/8 (12.5%)	1
Musculoskeletal and connective tissue disorders
Myalgia	2/8 (25%)	2
Joint Swelling	1/8 (12.5%)	1
Nervous system disorders
Peripheral Neuropathy	1/8 (12.5%)	1
Dizziness	1/8 (12.5%)	1
Memory Impairment	1/8 (12.5%)	1
Hemorrhage	2/8 (25%)	2
Psychiatric disorders
Insomnia	1/8 (12.5%)	1
Renal and urinary disorders
Acute Kidney Injury	1/8 (12.5%)	1
Renal lesion	1/8 (12.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory Failure	1/8 (12.5%)	1
Dyspnea	1/8 (12.5%)	1
Allergic Rhinitis	1/8 (12.5%)	1
Cough	1/8 (12.5%)	1
Hemoptysis	1/8 (12.5%)	1
Skin and subcutaneous tissue disorders
Dermatitis	1/8 (12.5%)	1
Pruritis	1/8 (12.5%)	1
Skin discoloration	1/8 (12.5%)	1
Vascular disorders
Hypertension	2/8 (25%)	2

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.