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

Trial Summary

What is the purpose of this trial?

Background: - Some people with cancer have solid tumors. Others have refractory leukemia. This may not go away after treatment. 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 of TURALIO(R). To see if it helps treat certain types of cancer. Eligibility: - People ages 3-35 with a solid tumor or leukemia that has returned or not responded to cancer therapies. Design: * Participants will be screened with: * Medical history * Physical exam * Blood and urine tests * Heart tests * Scans or other tests of the tumor * Participants will take TURALIO(R) as a capsule once daily for a 28-day cycle. They can do this for up to 2 years. * During the study, participants will have many tests and procedures. They include repeats of the screening tests. Participants will keep a diary of symptoms. * Participants with solid tumors will have scans or x-rays. * Participants with leukemia will have blood tests. They may have a bone marrow sample taken. * Some participants may have a biopsy. * When finished taking TURALIO(R), participants will have follow-up visits. They will repeat the screening tests and note side effects.

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 Turalio (Pexidartinib) safe for humans?

Turalio (Pexidartinib) has been approved for treating a specific type of tumor, but it comes with serious safety risks, including potentially fatal liver injury. A special program is in place to manage these risks, requiring doctors to monitor liver health closely and educate patients about the risks. ^{1 2 3 4 5}

What makes the drug Turalio unique for treating leukemia?

Turalio (Pexidartinib) is unique because it is an oral drug that targets specific proteins (tyrosine kinases) involved in cell growth, which may help in treating leukemia by disrupting cancer cell survival pathways. This mechanism is different from traditional chemotherapy, which generally targets rapidly dividing cells. ^{1 4 6 7 8}

Research Team

Rosandra N Kaplan, M.D.

Principal Investigator

National Cancer Institute (NCI)

Eligibility Criteria

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

References

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

Pexidartinib: First Approval. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Turalio risk evaluation and mitigation strategy for treatment of tenosynovial giant cell tumor: framework and experience. [2022]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Evaluation of Absorption and Metabolism-Based DDI Potential of Pexidartinib in Healthy Subjects. [2023]

4. United States 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). [2022]

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

Involvement of Rho-Associated Coiled-Coil Containing Kinase (ROCK) in BCR-ABL1 Tyrosine Kinase Inhibitor Cardiovascular Toxicity. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Real-World Patient Experience of Pexidartinib for Tenosynovial Giant-Cell Tumor. [2023]

7. United States 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. [2021]

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

A phase 1/2 study of chemosensitization with the CXCR4 antagonist plerixafor in relapsed or refractory acute myeloid leukemia. [2022]