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)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called elotuzumab for people with myelofibrosis, a condition where the bone marrow fails to produce enough healthy blood cells. The focus is on individuals with a specific mutation (JAK2) who cannot use JAK inhibitor therapy. The goal is to determine if elotuzumab can control the disease and improve blood cell counts and bone marrow function. This trial may suit adults with the JAK2 mutation who struggle with daily activities due to myelofibrosis and are not candidates for other targeted therapies. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

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 there any evidence suggesting that elotuzumab is likely to be safe for humans?

Research has shown that elotuzumab is generally safe. In earlier studies with patients who had myelofibrosis, most side effects were mild or moderate, meaning they were not severe and could be managed.

Elotuzumab is already used to treat multiple myeloma, a type of blood cancer, which supports its safety in humans. However, important warnings include the risk of low blood counts, blood clots, and potential harm to unborn babies.

Overall, elotuzumab appears to be well-tolerated, but it is crucial to be aware of these risks and discuss them with a healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Elotuzumab is unique because it offers a fresh approach to treating myelofibrosis by targeting specific proteins on the surface of certain immune cells. Unlike the standard treatments like JAK inhibitors, which primarily focus on reducing symptoms and slowing disease progression, elotuzumab works through a different mechanism by enhancing the immune system's ability to fight the disease. Researchers are excited about this treatment because it could provide an alternative for patients who don't respond well to existing therapies, offering hope for better management of myelofibrosis.

What evidence suggests that elotuzumab might be an effective treatment for myelofibrosis?

Research has shown that elotuzumab, which participants in this trial will receive, may help treat myelofibrosis, particularly in patients with the JAK2 mutation. A previous study found that 33% of patients responded positively, showing improvements in low red blood cell counts, platelet levels, and symptoms. Elotuzumab might help manage the disease and improve blood cell counts and bone marrow health. It is also known for its safety. These findings suggest that elotuzumab could be an effective treatment option for managing myelofibrosis. ^{1 3 6 7 8}

Who Is on the Research Team?

Prithviraj Bose

Principal Investigator

M.D. Anderson Cancer Center

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10431428/

A PILOT STUDY OF THE ANTI-SLAMF7 MONOCLONAL ... Elo is active in the treatment of MF and has an excellent safety profile. A total of 15 pts are planned to be accrued to this pilot study.

2. onclive.com onclive.com/view/data-for-elotuzumab-support-further-investigation-in-jak-inhibitor-based-combinations-in-myelofibrosis

Data for Elotuzumab Support Further Investigation in JAK ... The study reported a 33% overall response rate, with improvements in anemia, platelet response, and symptoms.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04517851

Elotuzumab for the Treatment of JAK2-Mutated Myelofibrosis Elotuzumab may help to control myelofibrosis and/or help to improve blood cell count and bone marrow function.

4. youtube.com youtube.com/watch?v=pZqx5zW97UE

Final results of a pilot study of elotuzumab in patients with ... Dr Bose highlights that advances in understanding myelofibrosis biology have led to the investigation of elotuzumab, which has shown promise in ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12102281/

Real world outcomes with elotuzumab-based therapies for ... At 2 years 38.8% and 53.7% of patients had ongoing sustained response for EPd and ERd, respectively. The median PFS for patients treated with ...

6. bmsaccesssupport.com bmsaccesssupport.com/empliciti/indications-important-safety-information

EMPLICITI® (elotuzumab) | Indications and Important ... REVLIMID & POMALYST Boxed WARNINGS. WARNING: EMBRYO-FETAL TOXICITY, HEMATOLOGIC TOXICITY, and VENOUS AND ARTERIAL THROMBOEMBOLISM.

7. empliciti.com empliciti.com/

EMPLICITI® (elotuzumab) | Official Patient Website Important Safety Information and Indications · WARNINGS FOR REVLIMID: Risk to unborn babies, risk of low blood counts and blood clots. · WARNINGS FOR POMALYST: ...

8. packageinserts.bms.com packageinserts.bms.com/pi/pi_empliciti.pdf

EMPLICITI U.S. Prescribing Information The safety data described in this section are based on ELOQUENT-3, a randomized, open-label clinical trial in patients with previously treated multiple myeloma.