LY2784544 for Blood Cancer

Not currently recruiting at 47 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Eli Lilly and Company

Must be taking: Hydroxyurea, Low-dose aspirin

Must not be taking: CYP3A4 agents, Warfarin

Disqualifiers: Heart failure, Infections, Other malignancy, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of a new treatment, LY2784544, for individuals with specific blood cancers, including polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF). The trial targets those who have not responded well to standard treatments, particularly ruxolitinib, or whose disease has worsened. Prospective participants should have one of these conditions and have tried other treatments without success. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

Participants must stop taking all previous approved therapies for Myeloproliferative Neoplasms (MPNs) at least 14 days before starting the trial, except for hydroxyurea and low-dose aspirin, which are allowed if stable. If you are on medications metabolized by certain liver enzymes or on warfarin, you may need to stop those as well.

Is there any evidence suggesting that LY2784544 is likely to be safe for humans?

Research shows that LY2784544, also called Gandotinib, targets a specific mutation linked to certain blood cancers. Previous patients generally tolerated it well. Earlier studies focused on assessing its safety and determining the optimal dose for future research.

The results indicated that most side effects were manageable, including mild to moderate issues like nausea, tiredness, and some changes in blood counts. However, reactions can vary among individuals. Since this trial is in a more advanced phase, evidence suggests the treatment is safe enough for broader testing. This information may reassure those considering joining the trial about its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for blood cancer?

Researchers are excited about LY2784544 for blood cancer because it targets the condition in a unique way. Unlike standard treatments like chemotherapy, which attack all rapidly dividing cells, LY2784544 is a targeted therapy designed to selectively inhibit the JAK2 enzyme. This enzyme is often mutated in certain blood cancers, leading to uncontrolled cell growth. By focusing specifically on this mutation, LY2784544 offers the potential for more precise treatment with potentially fewer side effects.

What evidence suggests that LY2784544 might be an effective treatment for blood cancer?

Studies have shown that LY2784544 targets a specific change in the JAK2 V617F gene, often linked to certain blood cancers. This drug blocks JAK2 activity, helping to reduce cancer cell numbers. Research indicates that LY2784544 can significantly lower cancer levels, especially in individuals with these gene changes, without harming healthy blood cells essential for normal body function. These findings suggest that LY2784544 could effectively treat conditions like polycythemia vera, essential thrombocythemia, and myelofibrosis. Participants in this trial will receive 120 mg of LY2784544 orally once daily for 6 cycles (168 days). ^{2 4 6 7 8}

Who Is on the Research Team?

Call 1-877-CTLilly (1-877-285-4559) or 1-317-615-4559 Mon- Fri 9 AM - 5 PM Eastern time (UTC/GMT -5 hours, EST)

Principal Investigator

Eli Lilly and Company

Are You a Good Fit for This Trial?

Adults with blood cancers like polycythemia vera, essential thrombocythemia, or myelofibrosis who haven't responded to or can't tolerate standard treatments (including ruxolitinib) may join. They should have a specific JAK2 mutation (except certain cohorts), be able to swallow pills, not be pregnant or breastfeeding, and agree to use contraception.

Inclusion Criteria

- Are able to swallow capsules

Have a diagnosis of polycythemia vera (PV), essential thrombocythemia (ET), or myelofibrosis (MF) as defined by the World Health Organization (WHO) diagnostic criteria for myeloproliferative neoplasms (Swerdlow et al. 2008) and meet the following additional subtype specific criteria:

- PV: have failed or is intolerant of standard therapies or refuses to take standard medications

Exclusion Criteria

Are currently enrolled in, or discontinued within the last 14 days from a clinical trial involving an investigational product or non-approved use of a drug or device, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study

Have a corrected QT (QTc) interval >470 millisecond (msec) using Bazett's formula

Have serious preexisting medical conditions that, in the opinion of the investigator would preclude participation in the study (for example a gastrointestinal disorder causing clinically significant symptoms such as nausea, vomiting, and diarrhea, or malabsorption syndrome)

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 120 mg of LY2784544 orally once daily for 6 cycles

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LY2784544

Trial Overview The trial is testing LY2784544 at 120 mg for those with myeloproliferative neoplasms who've had inadequate results from other therapies. It aims to see how well participants respond in terms of disease symptoms and progression.

How Is the Trial Designed?

Group I: 120 mg LY2784544 Experimental Treatment 1 Intervention

120 milligram (mg) administered orally once daily for 6 cycles (168 days)

Who Is Running the Clinical Trial?

Eli Lilly and Company

Lead Sponsor

Trials

2,708

Recruited

3,720,000+

Dr. Daniel Skovronsky

Eli Lilly and Company

Chief Medical Officer since 2018

MD from Harvard Medical School

David A. Ricks

Eli Lilly and Company

Chief Executive Officer since 2017

BSc from Purdue University, MBA from Indiana University

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3641321/

Discovery and characterization of LY2784544, a small ... These data suggest that LY2784544 has potential for development as a targeted agent against JAK2V617F and may have properties that allow suppression of ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8207330/

A phase 1 study of the Janus kinase 2 (JAK2)V617F inhibitor ... Gandotinib (LY2784544), a potent inhibitor of JAK2 activity, shows increased potency for the JAK2 V6l7F mutation.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0006497119461521

Poster III Efficacy of LY2784544, a Small Molecule Inhibitor ... LY2784544 selectively reduces JAK2 V617F tumor cell burden with no effect on erythroid progenitor cells.

4. nature.com nature.com/articles/bcj20136

Discovery and characterization of LY2784544, a small ... LY2784544 significantly reduced the Ba/F3-JAK2V617F-GFP tumor burden in the high-dose groups (40 and 80 mg/kg, BID) as compared with the vehicle ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT01594723

NCT01594723 | A Study of LY2784544 in Participants With ... The primary purpose of this study is to measure the response rate in participants with the myeloproliferative neoplasms (MPNs), polycythemia vera (PV), ...

6. cdn.caymanchem.com cdn.caymanchem.com/cdn/insert/16705.pdf

PRODUCT INFORMATION SAFETY DATA. This material should be considered hazardous until further information becomes available. Do not ingest, inhale, get in eyes, on skin, ...

7. ashpublications.org ashpublications.org/blood/article/122/21/665/71037/Phase-I-Study-Of-LY2784544-a-JAK2-Selective

Phase I Study Of LY2784544, a JAK2 Selective Inhibitor, In ... The study's primary objectives were to determine the safety and tolerability of LY2784544 and define a recommended oral daily dose for further ...

8. apexbt.com apexbt.com/ly2784544.html

LY2784544 (Gandotinib) – JAK2 Inhibitor LY2784544 (Gandotinib) is a selective JAK2 inhibitor that suppresses STAT signaling and proliferation, widely studied in hematology and oncology research.