Turalio for Leukemia

Recruiting at 1 trial location

Overseen By Elaine W Thomas

Age: < 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Cancer Institute (NCI)

Must not be taking: Warfarin, CYP3A4 drugs

Disqualifiers: Pregnancy, Active infection, Hepatitis, others

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

Compensation: Varies

Number of Visits: 3

Duration: Up to 104 weeks

54 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests TURALIO(R) (also known as PLX-3397 or Pexidartinib), a drug that may help treat cancers like solid tumors and leukemia that haven't responded to other treatments. The main goal is to find the safest dose, identify any side effects, and determine if the drug can shrink or stop tumor growth. People with a solid tumor or leukemia that has returned or didn't respond to other therapies might be a good fit for this trial. Participants will take the drug as a capsule once daily in 28-day cycles, undergoing regular tests and check-ups to monitor progress and any side effects. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this potentially groundbreaking therapy.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting TURALIO(R). Specifically, you must stop drugs that strongly affect CYP3A4, including some acid-reducing agents, at least 14 days or 5 half-lives before the study. If you're on corticosteroids or hydroxyurea for leukemia, you can continue as long as the dose hasn't increased in the 7 days before starting TURALIO(R).

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

A previous study demonstrated that TURALIO (also known as pexidartinib or PLX3397) maintained a consistent safety profile, with most participants experiencing similar side effects. In the ENLIVEN trial, 97% of patients experienced treatment-emergent adverse events, which are side effects occurring after starting a new treatment.

The FDA has already approved TURALIO for a different condition, indicating prior safety testing. However, researchers are still determining the safest dose for treating tumors and leukemia. As this trial is in an early phase, they are closely monitoring participants' reactions and potential side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Turalio is unique because it targets the CSF1R pathway, which is not commonly addressed by existing leukemia treatments. Most leukemia therapies focus on directly attacking cancer cells or inhibiting their growth. However, Turalio, with its active ingredient PLX3397, works by interfering with the signals that support cancer cell survival, potentially opening new avenues for treatment. Researchers are excited about this approach because it offers a different mechanism that might be effective for patients who have not responded to traditional therapies.

What evidence suggests that Turalio might be an effective treatment for leukemia?

Research has shown that Turalio, also known as PLX3397 or pexidartinib, may help treat certain types of cancer by blocking an enzyme that aids cancer cell growth. In earlier studies, Turalio shrank tumors or halted their growth, particularly in tenosynovial giant cell tumor cases. The drug's side effects are generally manageable, consistent with past research. While most data comes from studies on other cancers, these findings offer hope for its use in treating leukemia. Participants in this trial will take Turalio orally each day for a 28-day cycle to evaluate its effectiveness in leukemia. ^{3 6 7 8 9}

Who Is on the Research Team?

Rosandra N Kaplan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Are You a Good Fit for This Trial?

This trial is for young people aged 3-35 with certain types of cancer that haven't responded to other treatments. They should have solid tumors or specific leukemias (AML, ALL), be able to swallow capsules, and have a performance status indicating they can do daily activities. Patients must not have active infections or be pregnant, and need adequate blood counts and organ function.

Inclusion Criteria

I have NF1 and a cancerous tumor in my nerve sheath.

I am between 3 and 35 years old with a body size of at least 0.55 m^2.

I can swallow pills.

Exclusion Criteria

I am not on any cancer treatment except for specific leukemia therapy.

I do not have any severe illnesses or social situations that would stop me from following the study's requirements.

I do not have active hepatitis or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants take TURALIO(R) orally once daily for a 28-day cycle, repeated for up to 2 years

Up to 104 weeks

Regular visits for tests and procedures, including scans and blood tests

Follow-up

Participants are monitored for safety and effectiveness after treatment, repeating screening tests and noting side effects

4 weeks

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• PLX3397
• Turalio

Trial Overview Researchers are testing Turalio(R) (Pexidartinib) in children and young adults with refractory cancers including leukemia and solid tumors like neurofibromas associated with NF1. The goal is to find the highest safe dose of Turalio(R), understand its side effects, and see if it helps treat these cancers.

How Is the Trial Designed?

Group I: Phase I Experimental Treatment 1 Intervention

take oral drug daily for a 28 day cycle

PLX3397 is already approved in United States for the following indications:

Approved in United States as Turalio for:

• Symptomatic tenosynovial giant cell tumor (TGCT) associated with severe morbidity or functional limitations and not amenable to improvement with surgery

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

A survey of 83 patients taking pexidartinib for symptomatic tenosynovial giant-cell tumor (TGCT) showed that 78.3% reported improvement in overall symptoms and 77.2% in physical function after starting treatment.

Patients experienced significant reductions in worst stiffness and pain scores, indicating that pexidartinib effectively alleviates symptoms associated with TGCT, although 26.5% discontinued treatment due to various reasons.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor. Lin, F., Jacqueline Kwong, W., Pan, I., et al.[2023]

Pexidartinib, used for treating symptomatic tenosynovial giant cell tumor (TGCT), is associated with serious liver injury, leading to its approval under a mandatory Risk Evaluation and Mitigation Strategy (REMS).

The Turalio REMS program ensures that healthcare providers are educated on safe prescribing practices, requires monitoring of liver function, and includes a patient registry to track safety and potential liver toxicity, helping to balance treatment benefits with safety risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Turalio risk evaluation and mitigation strategy for treatment of tenosynovial giant cell tumor: framework and experience. Dharmani, C., Wang, E., Salas, M., et al.[2022]

Pexidartinib, an oral medication for tenosynovial giant cell tumor, shows significant changes in its exposure levels when taken with other drugs, highlighting the importance of understanding drug-drug interactions (DDIs) for safe and effective treatment.

The study found that certain medications, like itraconazole, can greatly increase pexidartinib levels in the body, while others, like rifampin, can significantly decrease its levels, suggesting that careful dosing adjustments are necessary when these drugs are used together.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of Absorption and Metabolism-Based DDI Potential of Pexidartinib in Healthy Subjects. Zahir, H., Greenberg, J., Shuster, D., et al.[2023]

In a phase 1/2 study involving 52 patients with relapsed or refractory acute myeloid leukemia (AML), the small molecule inhibitor plerixafor was safely combined with chemotherapy, showing no dose-limiting toxicities at a maximum dose of 0.24 mg/kg/d.

The combination treatment resulted in a 46% overall complete remission rate, and plerixafor effectively mobilized leukemic blasts into circulation, indicating its potential to enhance chemotherapy sensitivity by disrupting the CXCR4/CXCL12 interaction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. Uy, GL., Rettig, MP., Motabi, IH., et al.[2022]

In a phase 3b study involving 161 patients with polycythemia vera resistant or intolerant to hydroxyurea, ruxolitinib demonstrated a safety profile consistent with previous studies, with 37.9% of patients experiencing adverse events that required dose adjustments.

Ruxolitinib was effective, achieving hematocrit control in 45.3% of patients and significant spleen size reduction in 86.7%, indicating its potential as a viable treatment option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy findings from the open-label, multicenter, phase 3b, expanded treatment protocol study of ruxolitinib for treatment of patients with polycythemia vera who are resistant/intolerant to hydroxyurea and for whom no alternative treatments are available. Foltz, L., Pica, GM., Zerazhi, H., et al.[2021]

Pexidartinib (TURALIO™) is an FDA-approved oral medication specifically for adults with symptomatic tenosynovial giant cell tumor (TGCT) that cannot be treated with surgery, highlighting its targeted therapeutic use.

The approval was based on positive outcomes from the phase III ENLIVEN trial, and pexidartinib is also being explored for use in other cancers, indicating its potential broader application in oncology.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pexidartinib: First Approval. Lamb, YN.[2021]

Patients with Philadelphia chromosome-positive leukemia on second- and third-generation BCR-ABL1 tyrosine kinase inhibitors (TKIs) showed 1.6-fold greater ROCK activity compared to those on imatinib and healthy controls, indicating a potential link between elevated ROCK activity and cardiovascular adverse events (CVAEs).

In vitro studies revealed that dasatinib and ponatinib treatment caused endothelial dysfunction, which could be reversed by ROCK inhibition, suggesting that targeting ROCK may help reduce CVAEs in patients treated with these TKIs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Involvement of Rho-Associated Coiled-Coil Containing Kinase (ROCK) in BCR-ABL1 Tyrosine Kinase Inhibitor Cardiovascular Toxicity. Yu, B., Osman, AEG., Sladojevic, N., et al.[2023]

Plerixafor, when combined with high-dose chemotherapy, was well tolerated in a phase 1 trial involving 19 children and young adults with relapsed or refractory acute leukemias and myelodysplastic syndrome, with no dose-limiting toxicities observed.

While plerixafor successfully mobilized leukemic blasts into the bloodstream in most patients, clinical responses were limited, with only three patients achieving remission, indicating that while the treatment is safe, its effectiveness in this heavily pretreated group was modest.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 1 study of the CXCR4 antagonist plerixafor in combination with high-dose cytarabine and etoposide in children with relapsed or refractory acute leukemias or myelodysplastic syndrome: A Pediatric Oncology Experimental Therapeutics Investigators' Consortium study (POE 10-03). Cooper, TM., Sison, EAR., Baker, SD., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7189289/

A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in ... This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity against the FLT3 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02390752

Study Details | NCT02390752 | Phase I Trial of TURALIO(R ... Attempts will be made to enroll equal numbers of patients between the ages of 3 and 12 years and over 12 years of age to gain pharmacokinetic and safety data ...

3. ashpublications.org ashpublications.org/bloodadvances/article-abstract/4/8/1711/454467

A phase 1/2 study of the oral FLT3 inhibitor pexidartinib in ... This phase 1/2 study evaluated the safety, tolerability, and efficacy of the oral FLT3 inhibitor PLX3397 (pexidartinib), which has activity ...

4. daiichisankyo.us daiichisankyo.us/press-releases/-/article/turalio-final-long-term-data-showed-sustained-clinical-benefit-in-patients-with-tenosynovial-giant-cell-tumor-from-open-label-extension-of-enliven-phase-3-trial

TURALIO® Final Long-Term Data Showed Sustained ... The final results of the ENLIVEN trial show the potential for long-term tumor responses with TURALIO treatment with a safety profile consistent with earlier ...

5. asco.org asco.org/abstracts-presentations/ABSTRACT193653

Phase I study of pexidartinib (PLX3397) in children with ... Background: Refractory tumors remain a significant treatment challenge, and novel approaches targeting the tumor microenvironment may hold promise.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02390752

Study Details | NCT02390752 | Phase I Trial of TURALIO(R ... Researchers want to see if a drug called TURALIO(R) can shrink tumors or stop them from growing. Objectives: - To find the highest safe dose and side effects ...

7. clinicalstudies.info.nih.gov clinicalstudies.info.nih.gov/protocoldetails.aspx?id=15-C-0093&&query=Adult%20Acute%20Lymphocytic%20Leukemia

Phase I Trial of TURALIO (pexidartinib, PLX3397 ... Phase I Trial of TURALIO (pexidartinib, PLX3397) in Children and Young Adults with Refractory Leukemias and Refractory Solid Tumors Including Neurofibromatosis ...

8. onclive.com onclive.com/view/pexidartinib-shows-long-term-safety-and-efficacy-in-symptomatic-tgct

Pexidartinib Shows Long-Term Safety and Efficacy in ... The ENLIVEN trial demonstrated a consistent safety profile for pexidartinib, with 97% of patients experiencing treatment-emergent adverse ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT01349049

NCT01349049 | Phase 1/2 Safety and Efficacy of PLX3397 ... The purpose of this study is to evaluate the safety of study drug PLX3397 at 3 dose levels (800 mg/day, 1000 mg/day, and 1200 mg/day) and explore the ...