Clinical Trials /

Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis

NCT04517851

Description:

This phase I trial investigates how well elotuzumab works in treating patients with JAK2-mutated myelofibrosis. Elotuzumab may help to control myelofibrosis and/or help to improve blood cell count and bone marrow function.

Related Conditions:
  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
  • Official Title: A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Patients With Myelofibrosis

Clinical Trial IDs

  • ORG STUDY ID: 2020-0522
  • SECONDARY ID: NCI-2020-05712
  • SECONDARY ID: 2020-0522
  • NCT ID: NCT04517851

Conditions

  • Myelofibrosis Transformation in Essential Thrombocythemia
  • Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
  • Primary Myelofibrosis

Interventions

DrugSynonymsArms
ElotuzumabBMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063Treatment (elotuzumab)

Purpose

This phase I trial investigates how well elotuzumab works in treating patients with JAK2-mutated myelofibrosis. Elotuzumab may help to control myelofibrosis and/or help to improve blood cell count and bone marrow function.

Detailed Description

      PRIMARY OBJECTIVE:

      I. To obtain preliminary evidence of the efficacy of elotuzumab in patients with
      myelofibrosis (MF) by estimating the rate of overall response by International Working
      Group-Myeloproliferative Neoplasms Research and Treatment (IWG-MRT) 2013 criteria.

      SECONDARY OBJECTIVES:

      I. To characterize the safety and tolerability of elotuzumab in patients with MF.

      II. To assess for improvements in cytopenias and bone marrow fibrosis grade, splenomegaly and
      disease-related symptoms.

      III. To determine the duration of objective responses, if any, to elotuzumab. IV. To
      determine the time to next treatment.

      EXPLORATORY OBJECTIVES:

      I. To assess the proportion of circulating monocytes expressing the target of elotuzumab,
      SLAMF7, and any correlation of the same to the mutant JAK2 allele burden.

      II. To assess baseline levels of IL-1Ralpha and other cytokines and the effects of
      elotuzumab, if any, on these over time.

      III. To examine the effects of elotuzumab on fibrocyte count and differentiation, both in
      vitro and in vivo.

      IV. To assess clonal evolution, if any, in MF patients on elotuzumab treatment.

      OUTLINE:

      Patients receive elotuzumab intravenously (IV) over 1-4 hours on days 1, 8, 15, and 22 of
      cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1.
      Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or
      unacceptable toxicity.

      After completion of study treatment, patients are followed up at 30 days and then
      periodically thereafter.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (elotuzumab)ExperimentalPatients receive elotuzumab IV over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2. Beginning in cycle 3, patients receive elotuzumab IV over 1-4 hours on day 1. Treatment repeats every 28 days for up to 36 cycles in the absence of disease progression or unacceptable toxicity.
  • Elotuzumab

Eligibility Criteria

        Inclusion Criteria:

          -  Adults with JAK2 V617F+ primary myelofibrosis (PMF) or post-polycythemia vera
             (PV)/essential thrombocythemia myelofibrosis (ET-MF) who require treatment and have
             intermediate or higher risk disease (as assessed by the International Prognostic
             Scoring System for Myelodysplastic Syndrome [IPSS], Dynamic International Prognostic
             Scoring System [DIPSS], DIPSS-plus, Mutation-Enhanced Prognostic System for Transplant
             Age Patients with Primary Myelofibrosis [MIPSS70], MIPSS70-plus version [v] 2.0, or
             MYelofibrosis SECondary to PV and ET-Prognostic Model [MYSEC-PM]). The MYSEC-PM is to
             only be used for patients with post-PV/ET MF

          -  Patients must not be candidates for JAK inhibitor therapy in the opinion of the
             treating physician

          -  Bone marrow (BM) fibrosis grade 2 or 3 according to the European classification

          -  Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2 (Karnofsky
             performance status >= 60%)

          -  Absolute neutrophil count >= 0.5 x 10^9/L

          -  Direct bilirubin =< 1.5 x institutional upper limit of normal

          -  Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase
             [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT])
             =< 2.5 x institutional upper limit of normal unless felt to be due to liver
             involvement by MF/extramedullary hematopoiesis, in which case =< 5 x institutional
             upper limit of normal is permissible

          -  Creatinine =< 2 x institutional upper limit of normal OR creatinine clearance >= 30
             mL/min/1.73 m^2 for patients with creatinine levels above institutional normal

          -  Ability to understand and the willingness to sign a written informed consent document

          -  Women of child-bearing potential and men must agree to use adequate contraception
             (hormonal or barrier method of birth control; abstinence) prior to study entry and for
             the duration of study participation until 6 months after the last administration of
             elotuzumab. Should a woman become pregnant or suspect she is pregnant while she or her
             partner is participating in this study, she should inform her treating physician
             immediately. Women of child-bearing potential must have a negative pregnancy test. Men
             treated or enrolled on this protocol must also agree to use adequate contraception
             prior to the study, for the duration of study participation, and 6 months after the
             last administration of elotuzumab

        Exclusion Criteria:

          -  Splenic irradiation within the preceding 4 months

          -  Chemotherapy (other than hydroxyurea), interferons, IMiDs, danazol or other androgens,
             erythroid stimulating agents, or other MF-directed commercially available agents
             within 4 weeks prior to entering the study or those who have not recovered to baseline
             from adverse events due to agents administered more than 4 weeks earlier

          -  Other investigational agents within 4 half-lives prior to study entry

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to elotuzumab

          -  Patients with known central nervous system (CNS) involvement

          -  Prior allogeneic hematopoietic cell transplantation (allo-HCT) for MF

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, or psychiatric illness/social situations that would limit compliance with
             study requirements

          -  Known pregnancy or lactation

          -  Known human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus
             (HCV) positivity
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response (OR)
Time Frame:Up to completion of cycle 36 (1 cycle is 28 days)
Safety Issue:
Description:OR is defined as CR (complete response) +PR (partial response) + CI (clinical improvement), where CI includes clinical improvements in anemia, splenomegaly and/or symptoms. Will estimate the OR rate, along with the exact 95% confidence interval.

Secondary Outcome Measures

Measure:Incidence of adverse events
Time Frame:Up to 30 days post-treatment
Safety Issue:
Description:The method of Thall, Simon and Estey will be used to monitor for safety. The severity of the toxicities will be graded according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 whenever possible. Will follow standard reporting guidelines for adverse events. Safety data will be summarized by category, severity and frequency.
Measure:Duration of response
Time Frame:Up to 5 years
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate the duration of response where median and 95% confidence interval will be reported.
Measure:Time to next treatment
Time Frame:Up to 5 years
Safety Issue:
Description:The Kaplan-Meier method will be used to estimate the time to next treatment where median and 95% confidence interval will be reported.
Measure:Rates of complete response
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Rates of partial response
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Rates of clinical improvement
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Platelet response rate
Time Frame:Up to 5 years
Safety Issue:
Description:
Measure:Changes in bone marrow fibrosis grade
Time Frame:Baseline up to 5 years
Safety Issue:
Description:Will be assessed according to European classification.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:M.D. Anderson Cancer Center

Last Updated

August 14, 2020