Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
Primary Purpose
Myelofibrosis Transformation in Essential Thrombocythemia, Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, Primary Myelofibrosis
Status
Recruiting
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Elotuzumab
Questionnaire Administration
Sponsored by
About this trial
This is an interventional treatment trial for Myelofibrosis Transformation in Essential Thrombocythemia
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
Sites / Locations
- M D Anderson Cancer CenterRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Treatment (elotuzumab)
Arm Description
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.
Outcomes
Primary Outcome Measures
Overall response (OR)
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
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
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
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
Rates of partial response
Rates of clinical improvement
Platelet response rate
Changes in bone marrow fibrosis grade
Will be assessed according to European classification.
Full Information
NCT ID
NCT04517851
First Posted
August 14, 2020
Last Updated
August 22, 2023
Sponsor
M.D. Anderson Cancer Center
1. Study Identification
Unique Protocol Identification Number
NCT04517851
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
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 10, 2021 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Myelofibrosis Transformation in Essential Thrombocythemia, Polycythemia Vera, Post-Polycythemic Myelofibrosis Phase, Primary Myelofibrosis
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Treatment (elotuzumab)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Elotuzumab
Other Intervention Name(s)
BMS-901608, Empliciti, HuLuc-63, HuLuc63, PDL-063, PDL063
Intervention Description
Given IV
Intervention Type
Other
Intervention Name(s)
Questionnaire Administration
Intervention Description
Ancillary studies
Primary Outcome Measure Information:
Title
Overall response (OR)
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.
Time Frame
Up to completion of cycle 36 (1 cycle is 28 days)
Secondary Outcome Measure Information:
Title
Incidence of adverse events
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.
Time Frame
Up to 30 days post-treatment
Title
Duration of response
Description
The Kaplan-Meier method will be used to estimate the duration of response where median and 95% confidence interval will be reported.
Time Frame
Up to 5 years
Title
Time to next treatment
Description
The Kaplan-Meier method will be used to estimate the time to next treatment where median and 95% confidence interval will be reported.
Time Frame
Up to 5 years
Title
Rates of complete response
Time Frame
Up to 5 years
Title
Rates of partial response
Time Frame
Up to 5 years
Title
Rates of clinical improvement
Time Frame
Up to 5 years
Title
Platelet response rate
Time Frame
Up to 5 years
Title
Changes in bone marrow fibrosis grade
Description
Will be assessed according to European classification.
Time Frame
Baseline up to 5 years
Other Pre-specified Outcome Measures:
Title
Biomarker analysis
Description
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.
Time Frame
Up to 5 years
Title
Percentage of circulating SLAMF7high/CD16neg monocytes
Time Frame
Baseline and over time up to 5 years
Title
Serum IL-1Ralpha levels
Time Frame
Baseline and over time up to 5 years
Title
JAK2V617F allele burden in the bone marrow or blood
Time Frame
Baseline and over time up to 5 years
Title
Myeloid mutation panel (81-gene next generation sequencing panel) on serial bone marrow aspirates
Time Frame
Up to 5 years
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Prithviraj Bose
Phone
713-792-7747
Email
pbose@mdanderson.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Prithviraj Bose
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Prithviraj Bose
Phone
713-792-7747
Email
pbose@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Prithviraj Bose
12. IPD Sharing Statement
Links:
URL
http://www.mdanderson.org
Description
MD Anderson Cancer Center Website
Learn more about this trial
Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
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