Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis

Sponsor

M.D. Anderson Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04517851

Collaborator

(none)

Enrollment

Location

Arm

46.7

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Myelofibrosis Transformation in Essential Thrombocythemia Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase Primary Myelofibrosis	Biological: Elotuzumab Other: Questionnaire Administration	Phase 2

Detailed Description

PRIMARY OBJECTIVE:

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:

To characterize the safety and tolerability of elotuzumab in patients with MF.
To assess for improvements in cytopenias and bone marrow fibrosis grade, splenomegaly and disease-related symptoms.
To determine the duration of objective responses, if any, to elotuzumab. IV. To determine the time to next treatment.

EXPLORATORY OBJECTIVES:

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.
To assess baseline levels of IL-1Ralpha and other cytokines and the effects of elotuzumab, if any, on these over time.
To examine the effects of elotuzumab on fibrocyte count and differentiation, both in vitro and in vivo.
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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

15 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Patients With Myelofibrosis

Actual Study Start Date :

Feb 10, 2021

Anticipated Primary Completion Date :

Dec 31, 2024

Anticipated Study Completion Date :

Dec 31, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Treatment (elotuzumab) Patients 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.	Biological: Elotuzumab Given IV Other Names: BMS-901608 Empliciti HuLuc-63 HuLuc63 PDL-063 PDL063 Other: Questionnaire Administration Ancillary studies

Arm

Intervention/Treatment

Experimental: Treatment (elotuzumab)

Patients 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.

Biological: Elotuzumab

Given IV

Other Names:

BMS-901608

Empliciti

HuLuc-63

HuLuc63

PDL-063

PDL063

Other: Questionnaire Administration

Ancillary studies

Outcome Measures

Primary Outcome Measures

Overall response (OR) [Up to completion of cycle 36 (1 cycle is 28 days)]
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

Incidence of adverse events [Up to 30 days post-treatment]
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.
Duration of response [Up to 5 years]
The Kaplan-Meier method will be used to estimate the duration of response where median and 95% confidence interval will be reported.
Time to next treatment [Up to 5 years]
The Kaplan-Meier method will be used to estimate the time to next treatment where median and 95% confidence interval will be reported.
Rates of complete response [Up to 5 years]
Rates of partial response [Up to 5 years]
Rates of clinical improvement [Up to 5 years]
Platelet response rate [Up to 5 years]
Changes in bone marrow fibrosis grade [Baseline up to 5 years]
Will be assessed according to European classification.

Other Outcome Measures

Biomarker analysis [Up to 5 years]
Fisher's exact test will be used to assess the associations between biomarker expression (high versus low) and outcomes. Wilcoxon singed rank test will be applied to assess the change of biomarkers from baseline.
Percentage of circulating SLAMF7high/CD16neg monocytes [Baseline and over time up to 5 years]
Serum IL-1Ralpha levels [Baseline and over time up to 5 years]
JAK2V617F allele burden in the bone marrow or blood [Baseline and over time up to 5 years]
Myeloid mutation panel (81-gene next generation sequencing panel) on serial bone marrow aspirates [Up to 5 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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