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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
Sponsor:
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

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:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : February 10, 2021
Estimated Primary Completion Date : December 31, 2024
Estimated Study Completion Date : December 31, 2024


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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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.

  3. 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.

  4. Rates of complete response [ Time Frame: Up to 5 years ]
  5. Rates of partial response [ Time Frame: Up to 5 years ]
  6. Rates of clinical improvement [ Time Frame: Up to 5 years ]
  7. Platelet response rate [ Time Frame: Up to 5 years ]
  8. Changes in bone marrow fibrosis grade [ Time Frame: Baseline up to 5 years ]
    Will be assessed according to European classification.


Other Outcome Measures:
  1. 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.

  2. Percentage of circulating SLAMF7high/CD16neg monocytes [ Time Frame: Baseline and over time up to 5 years ]
  3. Serum IL-1Ralpha levels [ Time Frame: Baseline and over time up to 5 years ]
  4. JAK2V617F allele burden in the bone marrow or blood [ Time Frame: Baseline and over time up to 5 years ]
  5. Myeloid mutation panel (81-gene next generation sequencing panel) on serial bone marrow aspirates [ Time Frame: Up to 5 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

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


Contacts
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Contact: Prithviraj Bose 713-792-7747 pbose@mdanderson.org

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Prithviraj Bose    713-792-7747    pbose@mdanderson.org   
Principal Investigator: Prithviraj Bose         
Sponsors and Collaborators
M.D. Anderson Cancer Center
Investigators
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Principal Investigator: Prithviraj Bose M.D. Anderson Cancer Center
Additional Information:
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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT04517851    
Other Study ID Numbers: 2020-0522
NCI-2020-05712 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
2020-0522 ( Other Identifier: M D Anderson Cancer Center )
First Posted: August 18, 2020    Key Record Dates
Last Update Posted: November 14, 2022
Last Verified: November 2022

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Polycythemia Vera
Primary Myelofibrosis
Polycythemia
Thrombocytosis
Thrombocythemia, Essential
Myeloproliferative Disorders
Bone Marrow Diseases
Hematologic Diseases
Bone Marrow Neoplasms
Hematologic Neoplasms
Neoplasms by Site
Neoplasms
Blood Platelet Disorders
Blood Coagulation Disorders
Hemorrhagic Disorders
Elotuzumab
Antineoplastic Agents