Elotuzumab for Myelofibrosis

Overseen By Prithviraj Bose

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: M.D. Anderson Cancer Center

Must not be taking: Chemotherapy, Interferons, Androgens, others

Disqualifiers: CNS involvement, Uncontrolled illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 36 cycles (28 days each)

15 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications like chemotherapy (except hydroxyurea), interferons, and other specific treatments for myelofibrosis at least 4 weeks before joining. If you're on other investigational drugs, you need to stop them for a period based on their half-lives before starting the trial.

Is Elotuzumab safe for humans?

Elotuzumab, also known as Empliciti, has been used to treat multiple myeloma, and while specific safety data for myelofibrosis is not available, it has been studied for its potential to target certain cells in myelofibrosis. Generally, it is important to consult with healthcare providers for detailed safety information. ^{1 2 3 4 5}

How does the drug Elotuzumab differ from other treatments for myelofibrosis?

Elotuzumab is unique because it targets SLAMF7, a protein highly expressed on fibrocytes involved in myelofibrosis, and inhibits their differentiation, which is not a mechanism used by other treatments like JAK inhibitors. This approach could be particularly beneficial for patients with the JAK2V617F mutation, offering a novel way to address the disease. ^{2 5 6 7 8}

Research Team

Prithviraj Bose

Principal Investigator

M.D. Anderson Cancer Center

Eligibility Criteria

Adults with JAK2 V617F+ myelofibrosis needing treatment and at intermediate/high risk. They must have good performance status, specific blood counts, liver and kidney function levels, agree to use contraception, and not be candidates for JAK inhibitor therapy. Excluded are those recently on certain treatments or with allergies to similar drugs, CNS involvement, uncontrolled illnesses, pregnancy/lactation, HIV/HBV/HCV positivity or prior transplants.

Inclusion Criteria

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

I have a type of blood cancer called myelofibrosis with a specific mutation and it's considered intermediate or high risk.

My bone marrow fibrosis is moderate to severe.

Exclusion Criteria

I have not had radiation to my spleen in the last 4 months.

My cancer has spread to my brain or spinal cord.

I haven't taken any experimental drugs recently.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive elotuzumab intravenously over 1-4 hours on days 1, 8, 15, and 22 of cycles 1-2, and on day 1 from cycle 3 onwards. Treatment repeats every 28 days for up to 36 cycles.

Up to 36 cycles (28 days each)

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and periodically thereafter.

Up to 5 years

Treatment Details

Interventions

• Elotuzumab

Trial Overview The trial is testing Elotuzumab's effectiveness in treating patients with JAK2-mutated myelofibrosis to control the disease and improve blood cell count and bone marrow function. It also includes questionnaire administration to gather patient-reported outcomes.

Participant Groups

Group I: Treatment (elotuzumab) Experimental Treatment 2 Interventions

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.

Elotuzumab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Empliciti for:

• Multiple myeloma

Approved in European Union as Empliciti for:

• Multiple myeloma

Approved in Canada as Empliciti for:

• Multiple myeloma

Who Is Running the Clinical Trial?

M.D. Anderson Cancer Center

Lead Sponsor

Trials

3,107

Recruited

1,813,000+

Findings from Research

Fedratinib has been approved by the FDA as a treatment for myelofibrosis, marking it as the second drug and second JAK inhibitor approved for this condition.

In the phase III JAKARTA trial, fedratinib significantly reduced symptoms of myelofibrosis compared to a placebo, but it carries a Boxed Warning for the risk of encephalopathy, highlighting the need for careful monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fedratinib Becomes New Option in Myelofibrosis. [2020]

In a study of 219 patients with myelofibrosis, ruxolitinib demonstrated a significant efficacy advantage over the best available therapy, with 28% of patients achieving at least a 35% reduction in spleen volume at 48 weeks, compared to 0% in the control group.

Ruxolitinib not only reduced spleen size but also improved overall quality of life and disease symptoms, with manageable side effects, primarily hematologic issues like thrombocytopenia and anemia, indicating it is a safe and effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. Harrison, C., Kiladjian, JJ., Al-Ali, HK., et al.[2022]

JAK inhibitors have significantly improved treatment options for myelofibrosis (MF) by alleviating symptoms, reducing spleen size, and enhancing quality of life, although they may lead to worsening blood cell counts (cytopenias).

Despite their benefits, JAK inhibitors do not stop disease progression or prevent the transformation to leukemia, and their impact on overall survival remains uncertain.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

JAK inhibitors in the treatment of myelofibrosis. Levavi, H., Hoffman, R., Marcellino, BK.[2022]

Ruxolitinib, a JAK inhibitor approved for myelofibrosis, does not cure the disease, highlighting the need for new therapies with different mechanisms of action.

Several promising new agents, including heat shock protein inhibitors and monoclonal antibodies, are being tested in clinical trials and may help overcome resistance to JAK2 inhibitors and address challenges like bone marrow fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

What is next beyond janus kinase 2 inhibitors for primary myelofibrosis? Santos, FP., Verstovsek, S.[2023]

References

1. United States pubmed.ncbi.nlm.nih.gov

Fedratinib Becomes New Option in Myelofibrosis. [2020]

2. United States pubmed.ncbi.nlm.nih.gov

JAK inhibition with ruxolitinib versus best available therapy for myelofibrosis. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

JAK inhibitors in the treatment of myelofibrosis. [2022]

4. New Zealand pubmed.ncbi.nlm.nih.gov

Emerging treatment options for myelofibrosis: focus on pacritinib. [2020]

5. Japan pubmed.ncbi.nlm.nih.gov

[The role of fibrocytes in myelofibrosis and fibrocyte regulation as a novel treatment approach]. [2020]

6. United States pubmed.ncbi.nlm.nih.gov

Conventional and experimental drug therapy in myelofibrosis with myeloid metaplasia. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

What is next beyond janus kinase 2 inhibitors for primary myelofibrosis? [2023]

8. Spain pubmed.ncbi.nlm.nih.gov

[Effectiveness and safety of lenalidomide in myelofibrosis patients: a case series from the Spanish compassionate use program]. [2018]