Adding ruxolitinib to standard radiation and temozolomide for newly diagnosed glioblastoma

Randomized Phase 2 Trial of Ruxolitinib in Combination With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma.

This trial will try whether adding the oral drug ruxolitinib to standard radiation and temozolomide helps adults newly diagnosed with glioblastoma.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 190 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Baptist Health South Florida (other)
• Drugs / interventions: ruxolitinib, radiation
• Locations: 1 site (Miami, Florida)
• Trial ID: NCT06991101 on ClinicalTrials.gov

What this trial studies

This is a randomized Phase 2 trial comparing standard radiation plus temozolomide with or without the addition of ruxolitinib in adults with newly diagnosed, IDH‑wildtype glioblastoma. Eligible patients (KPS ≥70) are randomized 1:1 to receive either standard therapy or standard therapy plus oral ruxolitinib, with safety and tumor outcomes tracked over time. Patients must have sufficient tumor tissue for MGMT and IDH testing and adequate organ and bone marrow function before randomization. The trial is led by Baptist Health South Florida at the Miami Cancer Institute in collaboration with Incyte.

Who should consider this trial

Good fit: Adults (≥18) with newly diagnosed, histologically confirmed IDH‑wildtype glioblastoma, KPS ≥70, adequate organ and bone marrow function, and available tumor tissue for MGMT and IDH testing are the intended candidates.

Not a fit: Patients with recurrent glioblastoma, non–IDH‑wildtype tumors, poor performance status (KPS <70), or inadequate organ or bone marrow function are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, adding ruxolitinib could slow tumor progression or extend survival compared with standard therapy alone.

How similar studies have performed: Previous efforts targeting the JAK/STAT pathway including ruxolitinib in solid tumors and gliomas have shown limited or mixed results, so this approach remains exploratory in newly diagnosed glioblastoma.

Eligibility criteria

Inclusion Criteria:

1. Provision of signed informed consent form.
2. Stated willingness to comply with all study procedures and availability for the duration of the study.
3. Individuals of any sex, gender, race, or ethnicity ≥ 18 years of age.
4. Histologically confirmed glioblastoma as defined by the World Health Organization (WHO) 2021 Criteria (IDH-wildtype) that is either methylated, unmethylated, or indeterminate MGMT.
5. Confirmation that patient has sufficient tissue to undergo MGMT and IDH testing, as mandated.
6. Must have a Karnofsky performance status (KPS) ≥ 70% (i.e., the patient must be able to care for themself with occasional help from others).
7. Adequate organ (liver and renal) and bone marrow function within 14 days before randomization. For all parameters listed below, the most recent results available must be used:

   1. Absolute neutrophil count (ANC) ≥ 1500/mm3. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.
   2. Platelet count ≥ 100,000/mm3. Note: Platelet transfusion is not allowed within 1 week prior to registration.
   3. Total bilirubin (TBL) ≤ 1.5 × institutional upper limit of normal (ULN).
   4. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
   5. Serum albumin ≥ 2.5 g/dL.
8. Patients able to become pregnant: use of highly effective contraception for at least one (1) month prior to screening and agreement to use such a method. Should a participant become pregnant or suspect that they are pregnant while participating in this study, they should notify the treating physician immediately. Such individuals must have a negative pregnancy test.
9. Patients must have no concurrent malignancy except curatively treated early-stage bladder and prostate cancer that has been completed resected, basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix and breast, adequately treated stage I or II cancer from which the patient is in complete remission. Patients with other prior malignancies must be disease-free for ≥ 3 years.

Exclusion Criteria:

1. Patients who are pregnant or breast-feeding. The anti-proliferative activity of this experimental drug and temozolomide may be harmful to the developing fetus or nursing infant.
2. Patients receiving concurrent therapy for their brain tumor (e.g., chemotherapeutics or investigational agents).
3. Patients with a concurrent or prior malignancy are ineligible unless they are patients with curatively treated carcinoma-in-situ or basal cell carcinoma of the skin. Patients who have been free of disease (any prior malignancy) for at least 3 years are eligible for this study.
4. Patients who have had repeat craniotomy for tumor therapy after receiving radiation therapy and temozolomide treatment.
5. Patients who received other chemotherapeutics or investigational agents in addition to their radiation therapy and concomitant temozolomide treatment.
6. Patient has previously taken ruxolitinib or is allergic to components of the study drug.
7. Patients using warfarin.
8. Uncontrolled immunodeficiency virus infection or active tuberculosis.
9. Patients with active serious infections requiring systemic therapy.
10. Known Active hepatitis B virus (HBV) or hepatitis C virus infection that requires treatment or at risk for HBV reactivation. At risk for HBV reactivation is defined as hepatitis B surface antigen positive or anti-hepatitis B core antibody positive. Participants with previous positive serology results must have negative polymerase chain reaction results.
11. Patient has significant abnormalities on screening electrocardiogram (EKG) and active and significant cardiovascular disease such as uncontrolled or symptomatic arrhythmias, New York Heart Association (NYHA) Grade ≥2 heart failure, uncontrolled hypertension, valvular disease, pericarditis, myocardial infarction, or other thrombosis events like including pulmonary embolism or deep vein thrombosis within 6 months of screening.
12. Any other serious medical/psychiatric condition, in the judgement of the investigator, that likely to interfere or limit compliance with study requirements/treatment.

Where this trial is running

Miami, Florida

• Miami Cancer Institute at Baptist Health, Inc. — Miami, Florida, United States (RECRUITING)

Study contacts

• Principal investigator: Manmeet Ahluwalia, M.D., MBA — Miami Cancer Institute at Baptist Health, Inc.
• Study coordinator: Manmeet Ahluwalia, M.D., MBA

Conditions: Glioblastoma, Brain Cancer, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain, Glioblastoma Multiforme, Adult, MGMT-Unmethylated Glioblastoma, MGMT-Methylated Glioblastoma