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

NCT02805868 | Withdrawn Early Phase 1 DMC

• 4 other identifiers: NU 16H01STU00202680P30CA060553NCI-2016-00685
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

The main purpose of this investigational research study is to determine how safe and tolerable the study drug siltuximab is in patients with myelofibrosis (MF). This medication has been approved by the FDA for another condition (multicentric castleman's disease (MCD), but not for myelofibrosis (MF). In MCD, siltuximab resulted in improvement in symptoms and anemia. While MCD and MF are different diseases, they share some common features including a protein call interleukin-6 (IL-6) that may be important in causing symptoms of MCD and MF.

Conditions

Myelofibrosis; Polycythemia Vera; Primary Myelofibrosis; Thrombocytopenia

Keywords

Severe; Anemia; Aplastic; Post-Polycythemic; Transformation; Thrombocythemia; Essential

Outcome Measures

Primary Outcomes (1)

• Incidence of Adverse Events

  To evaluate safety and tolerability of the drug siltuximab in the myelofibrosis patient population. Adverse events will be assessed by type, timing, frequency, and attribution and will be graded according to the NCI's common terminology criteria, version 4.03.

  Up to 30 days after last treatment

Secondary Outcomes (4)

• Clinical Improvement (CI): changes in symptoms

  At baseline and after cycle 3 (9 weeks)

• Clinical Improvement (CI): splenomegaly

  At baseline and after cycle 3 (9 weeks)

• Clinical Improvement (CI): Anemia response

  At baseline and after cycle 3 (9 weeks)

• Overall Response Rate (ORR)

  After 6 cycles of treatment (18 weeks)

Other Outcomes (3)

• Iron Dysregulation

  At baseline, after cycle 3 (9 weeks), and after cycle 6 (18 weeks)

• Changes in inflammatory stress: C-reactive protein (CRP)

  At baseline, after cycle 3 (9 weeks), and after cycle 6 (18 weeks)

• Changes in inflammatory stress: hepcidin levels

  At baseline, after cycle 3 (9 weeks), and after cycle 6 (18 weeks)

Study Arms (1)

Treatment (siltuximab)

EXPERIMENTAL

Patients receive siltuximab IV over 60 minutes on day 1. Patients also undergo bone marrow biopsy and aspiration at baseline and at the end of treatment (within 30 days of last siltuximab dose) or as clinically indicated. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. Patients who are responding after 6 courses may receive additional siltuximab treatment for up to 1 year at the discretion of the study doctor.

Procedure: Bone Marrow Aspiration and Biopsy; Other: Laboratory Biomarker Analysis; Biological: Siltuximab

Interventions

Bone Marrow Aspiration and Biopsy PROCEDURE

Undergo bone marrow aspiration and biopsy

Treatment (siltuximab)

Laboratory Biomarker Analysis OTHER

Correlative studies

Treatment (siltuximab)

Siltuximab BIOLOGICAL

Given IV

Also known as: Anti-IL-6 Chimeric Monoclonal Antibody, cCLB8, CNTO 328, CNTO-328, Sylvant

Treatment (siltuximab)

Eligibility Criteria

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

You may qualify if:

• Patients must have a histologically confirmed diagnosis of primary myelofibrosis (PMF), post-polycythemia vera (post-PV) myelofibrosis (MF), or post-essential thrombocythemia (post-ET) MF using World Health Organization Criteria
• Patients must have disease that requires therapy, including intermediate-1, intermediate-2, or high-risk disease according to the International Prognostic Scoring System (IPSS) or Dynamic-IPSS
• Patients must be off myeloproliferative neoplasm (MPN) directed therapy, such as Janus kinase (JAK)-inhibitors, for at least 2 weeks prior to administration of the study drug; NOTE: This does not include supportive transfusion, or hydroxyurea; these must be stopped prior to first day of treatment, but no wash -out period is required
• Patients must be resistant to, intolerant of, or ineligible for JAK2 inhibitor therapy, based on severe anemia or thrombocytopenia
• Patients must exhibit an Eastern Cooperative Oncology Group (ECOG) performance status of =\< 2
• New York Heart Association functional classification for congestive heart failure (NYHA CHF) \< 3
• Patients must have clinical laboratory values meeting the following criteria within 28 days prior to registration:
• Absolute neutrophil count \>= 1.0 x 10\^9/L (without growth factor support)
• Platelet count \>= 20 x 10\^9/L (without transfusion support within 2 weeks of registration)
• Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x upper limit of normal (ULN)
• Alkaline phosphatase =\< 2.5 x ULN
• Total bilirubin =\< 2.5 x upper limit of normal (ULN) except if the elevation is due to Gilbert's syndrome (allowable at =\< 5 x ULN) or myelofibrosis (per principle investigator \[PI\] discretion)
• Calculated creatinine clearance \> 20 mL/min per institutional standard
• Before enrollment, a woman must be one of the following:
• Not of childbearing potential, defined as:

You may not qualify if:

• Patients with prior exposure to agents targeting interleukin 6 (IL -6) or the IL-6 receptor are not eligible
• Patients with another malignancy, unless they have been disease free for 2 years prior to registration, with the exception of
• Basal cell or non-metastatic squamous cell carcinoma of the skin
• Cervical carcinoma in situ or International Federation of Gynecology and Obstetrics (FIGO) stage 1 carcinoma of the cervix
• Patients who have an uncontrolled intercurrent illness including, but not limited to any of the following, are not eligible:
• Ongoing or active infection requiring concurrent systemic antibiotic treatment: there is no mandatory duration of time that a patient has to be off antibiotics, but the treating physician has to deem the infection as effectively treated prior to enrollment
• Symptomatic congestive heart failure
• Unstable angina pectoris
• Cardiac arrhythmia
• Psychiatric illness/social situations that would limit compliance with study requirements
• Any other illness or condition that the treating investigator feels would interfere with study compliance or would compromise the patient's safety or study endpoints
• Patients who have received vaccination with live attenuated vaccines within 6 months prior to registration are not eligible
• Patients who are on any prohibited medication; they have to be have a wash-out period of at least 2 weeks prior to registration, in order to be eligible for the study
• Patients with clinically significant infection, including known human immunodeficiency virus (HIV), human herpesvirus-8 (HHV-8), hepatitis C infection, or known hepatitis B surface antigen positivity are not eligible
• Female patients who are pregnant or breast-feeding are not eligible; NOTE: A woman who is planning to become pregnant or a man who plans to father a child while enrolled in this study or within 3 months after the last dose of study agent should likewise not be considered for this study

Sponsors & Collaborators

• Northwestern University: lead
• National Cancer Institute (NCI): collaborator

MeSH Terms

Conditions

Primary Myelofibrosis; Polycythemia Vera; Thrombocytopenia; Lymphoma, Follicular; Anemia; Thrombocytosis

Interventions

Biopsy; siltuximab

Condition Hierarchy (Ancestors)

Myeloproliferative Disorders; Bone Marrow Diseases; Hematologic Diseases; Hemic and Lymphatic Diseases; Bone Marrow Neoplasms; Hematologic Neoplasms; Neoplasms by Site; Neoplasms; Blood Platelet Disorders; Cytopenia; Lymphoma, Non-Hodgkin; Lymphoma; Neoplasms by Histologic Type; Lymphoproliferative Disorders; Lymphatic Diseases; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Brady Stein, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 10, 2016
• First Posted: June 20, 2016
• Study Start: June 1, 2016
• Primary Completion: February 1, 2019
• Last Updated: October 24, 2016

Record last verified: 2016-10