Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis
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|ClinicalTrials.gov Identifier: NCT04517851|
Recruitment Status : Recruiting
First Posted : August 18, 2020
Last Update Posted : November 14, 2022
|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|
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.
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.
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.
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Pilot Study of the Anti-SLAMF7 Monoclonal Antibody, Elotuzumab, in Patients With Myelofibrosis|
|Actual Study Start Date :||February 10, 2021|
|Estimated Primary Completion Date :||December 31, 2024|
|Estimated Study Completion Date :||December 31, 2024|
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.
Other: Questionnaire Administration
- Overall response (OR) [ Time Frame: 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.
- Incidence of adverse events [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Up to 5 years ]
- Rates of partial response [ Time Frame: Up to 5 years ]
- Rates of clinical improvement [ Time Frame: Up to 5 years ]
- Platelet response rate [ Time Frame: Up to 5 years ]
- Changes in bone marrow fibrosis grade [ Time Frame: Baseline up to 5 years ]Will be assessed according to European classification.
- Biomarker analysis [ Time Frame: 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 [ Time Frame: Baseline and over time up to 5 years ]
- Serum IL-1Ralpha levels [ Time Frame: Baseline and over time up to 5 years ]
- JAK2V617F allele burden in the bone marrow or blood [ Time Frame: Baseline and over time up to 5 years ]
- Myeloid mutation panel (81-gene next generation sequencing panel) on serial bone marrow aspirates [ Time Frame: Up to 5 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04517851
|Contact: Prithviraj Boseemail@example.com|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Prithviraj Bose 713-792-7747 firstname.lastname@example.org|
|Principal Investigator: Prithviraj Bose|
|Principal Investigator:||Prithviraj Bose||M.D. Anderson Cancer Center|