Clinical trial NCT04517851: Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
Official title: A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Patients With Myelofibrosis
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Myelofibrosis Transformation in Essential Thrombocythemia
Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase
Primary Myelofibrosis
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
First posted: 2020-08-18
Enrollment: 15
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This phase II 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.

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

Primary outcomes:
measure: Overall response (OR)
timeFrame: Up to completion of cycle 36 (1 cycle is 28 days)
Secondary outcomes:
measure: Incidence of adverse events
timeFrame: Up to 30 days post-treatment
measure: Duration of response
timeFrame: Up to 5 years
measure: Time to next treatment
timeFrame: Up to 5 years
measure: Rates of complete response
timeFrame: Up to 5 years
measure: Rates of partial response
timeFrame: Up to 5 years
measure: Rates of clinical improvement
timeFrame: Up to 5 years
measure: Platelet response rate
timeFrame: Up to 5 years
measure: Changes in bone marrow fibrosis grade
timeFrame: Baseline up to 5 years
Other outcomes:
measure: Biomarker analysis
timeFrame: Up to 5 years
measure: Percentage of circulating SLAMF7high/CD16neg monocytes
timeFrame: Baseline and over time up to 5 years
measure: Serum IL-1Ralpha levels
timeFrame: Baseline and over time up to 5 years
measure: JAK2V617F allele burden in the bone marrow or blood
timeFrame: Baseline and over time up to 5 years
measure: Myeloid mutation panel (81-gene next generation sequencing panel) on serial bone marrow aspirates
timeFrame: Up to 5 years
Locations:
city: Houston
country: United States
facility: M D Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: Prithviraj Bose
role: PRINCIPAL_INVESTIGATOR
References: