GlioblastomaPhase 2NCT06991101
Ruxolitinib With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma
A Phase 2 study testing Ruxolitinib, Temozolomide and Radiation Therapy in people with Glioblastoma and Brain Cancer, run by Baptist Health South Florida at 2 sites in United States.
Trial summary
The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Glioblastoma, Brain Cancer, Glioblastoma Multiforme
- What is being tested?
- Ruxolitinib, Temozolomide and Radiation Therapy
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 190 participants
- Where
- 2 sitesUnited States
- Study dates
- 3 Dec 2025to Dec 2030
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Provision of signed informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Individuals of any sex, gender, race, or ethnicity ≥ 18 years of age.
- Histologically confirmed glioblastoma as defined by the World Health Organization (WHO) 2021 Criteria (IDH-wildtype) that is either methylated, unmethylated, or indeterminate MGMT.
- Must have a Karnofsky performance status (KPS) ≥ 70% (i.e., the patient must be able to care for themself with occasional help from others).
- 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:
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- Absolute neutrophil count (ANC) ≥ 1500/mm³. Note: Granulocyte-colony stimulating factor (G-CSF) administration is not allowed within 1 week prior to screening assessment.
- Platelet count ≥ 100,000/mm³. Note: Platelet transfusion is not allowed within 1 week prior to registration.
- Total bilirubin (TBL) ≤ 1.5 × institutional upper limit of normal (ULN).
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 3 × ULN.
- Serum albumin ≥ 2.5 g/dL.
- Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 50 mL/min
- CrCl to be calculated using Cockcroft-Gault formula:
- If actual body weight < Ideal body weight (IBW), use actual body weight
- If ideal body weight < actual body weight < 1.25 ideal body weight, use ideal body weight
- If actual body weight ≥ 1.25 ideal body weight, use adjusted body weight
- Adjusted body weight = Ideal body weight + 0.4 (Actual body weight - ideal body weight)
- IBW: Male IBW = 50 kg + 2.3 kg per inch over 5 feet or Female IBW = 45.5 kg + 2.3 kg per inch over 5 feet *Note: for patients whose serum creatinine exceeds 1.5 × ULN, a calculated creatinine ≥ 50 mL/min is required for eligibility
- 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.
- 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.
- The ability to swallow
Who cannot join
- 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.
- Patients receiving concurrent therapy for their brain tumor (e.g., chemotherapeutics or investigational agents).
- 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.
- Patient has previously taken ruxolitinib or is allergic to any components of the study drug.
- Patients using warfarin.
- Uncontrolled immunodeficiency virus infection or active tuberculosis.
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- Patients with active serious infections requiring systemic therapy.
- 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.
- 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.
- Patients who have obtained the following vaccines ≤ 6 weeks prior to the start of the study: adenovirus, BCG, chikungunya, cholera, dengue, Ebola Zaire, Influenza (live/attenuated), Japanese encephalitis (live/attenuated), measles, mumps, rubella, varicella, poliovirus (live/bivalent/oral), rotavirus, smallpox (live), typhoid, yellow fever, zoster (live/attenuated).
- Any other serious medical/psychiatric condition, in the judgement of the investigator, that likely to interfere or limit compliance with study requirements/treatment.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
WCI Multisite Research Program contact
United States2 sites, 2 recruiting
- Recruiting
Baptist Health Herbert Wertheim Cancer Institute
Miami, Florida, 33176
WCI Multisite Research Program, 786-596-2000, MCIMultisiteResearch@baptisthealth.net
Manmeet Ahluwalia, M.D., MBA
- Recruiting
New York University Langone's Perlmutter Cancer Institute
New York, New York, 10016
Alexandra Miller, M.D., Ph.D., Alexandra.Miller2@nyulangone.org
About this study
Official title: Randomized Phase 2 Trial of Ruxolitinib in Combination With Radiation and Temozolomide Compared to Radiation and Temozolomide for Newly Diagnosed Glioblastoma.
The purpose of this research is to test the safety and effectiveness of the investigational drug ruxolitinib when it is combined with standard of care treatment (radiation therapy and temozolomide) for the treatment of newly diagnosed glioblastoma. Half the people in the study will be assigned to take the study drug ruxolitinib in addition to the standard of care temozolomide and radiation therapy and the other half will be assigned to the standard of care temozolomide and radiation therapy only. This assignment will be randomized in a 1-to-1 ratio, like the flip of a coin.
- Conditions
- Glioblastoma, Brain Cancer, Glioblastoma Multiforme, Glioblastoma Multiforme of Brain, Glioblastoma Multiforme, Adult, MGMT-Unmethylated Glioblastoma
- Being tested
- Ruxolitinib, Temozolomide, Radiation Therapy
- Medical subject headings
- Glioblastoma, Brain Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RuxolitinibDrug
Also called Jakavi
"During Radiation Therapy" phase: 20 mg ruxolitinib will be self-administered orally (PO) twice every day (BID), starting on Day 1 for 6 weeks. Then there will be a 4-week break after radiotherapy is complete.
"Maintenance" phase: Occurs thirty days (4 weeks) after receiving the last dose of radiotherapy. Ruxolitinib 20 mg will be self-administered PO BID, starting on Day 1 in consecutive 28-day cycles.
Either phase:
Aside from the 30-day break, ruxolitinib will be continued daily until disease progression or treatment intolerance. Ruxolitinib should be administered at approximately the same time each day. The tablets should be swallowed whole with water and should not be opened, broken, or chewed. The dose may be reduced in the case of certain adverse events.
TemozolomideDrug
Also called Temodar
"During Radiation Therapy" phase: 75 mg/m^2 will be self-administered PO once every day, starting on Day 1, for 6 weeks. Then there will be a 4-week break after radiotherapy is complete.
"Maintenance" phase: Occurs thirty days (4 weeks) after receiving the last dose of radiotherapy. Temozolomide 150-200 mg/m^2 will be self-administered PO BID, starting on Day 1 to Day 5 of each cycle for six cycles.
Either phase:
The dose may be reduced in the case of certain adverse events.
Radiation TherapyRadiation
Radiation will be administered every weekday (Monday to Friday) in 2 Gy fractions for 30 fractions during a 6-week period (60 Gy total).
| Study group | Role | What they receive |
|---|---|---|
| Ruxolitinib plus Radiation and Temozolomide | Experimental | There will be two phases of drug administration: (1) Ruxolitinib and temozolomide will be administered "During Radiation Therapy" and (2) Maintenance phase after radiation therapy is complete. Receives: Drug: Ruxolitinib; Drug: Temozolomide; Radiation: Radiation Therapy |
| Radiation and Temozolomide | Active comparator | There will be two phases of drug administration: (1) Temozolomide will be administered "During Radiation Therapy" and (2) Maintenance phase after radiation therapy is complete. Receives: Drug: Temozolomide; Radiation: Radiation Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall survival (OS) at end of study
OS is defined as the time from first treatment until the date of death from any cause at the end of the study. Participants who are lost to follow-up will be censored at the time of the last follow-up.
Measured: 4 years
Secondary outcomes (9)
OS at 12 months
OS is defined as the time from first treatment until the date of death from any cause at 12 months. Participants who are lost to follow-up will be censored at the time of the last follow-up.
Measured: 12 months
Progression-free survival (PFS) at 6 months
PFS is defined as the time from treatment to the first progressive disease (PD) using Response Assessment in Neuro-Oncology 2.0 (RANO 2.0) criteria or death due to any cause, whichever occurs first by 6 months. Participants lost to follow-up will be censored at the last follow-up. PD is defined as any of the following:
- ≥ 25% increase in sum of products of perpendicular diameters or ≥ 40% increase in total volume of enhancing lesions compared to the smallest tumor measurement obtained at baseline or best response and sustained for at least 4 weeks
- Any new measurable (> 10mm × 10mm) enhancing lesions if baseline or best response demonstrated no measurable enhancing disease
- Appearance of definite leptomeningeal disease
- Unequivocal progression of existing non-target lesions
- Clear clinical deterioration not attributable to decreased corticosteroid dose or other causes apart from tumor
- Failure to return for evaluation due to death or deteriorating condition
Measured: 6 months
PFS at 12 months
PFS is defined as defined as the time from treatment to the first documented PD using RANO 2.0 criteria or death due to any cause, whichever occurs first by 12 months. Participants who are lost to follow-up will be censored at the time of the last follow-up. PD is defined above for PFS at 6 months.
Measured: 12 months
Objective response rate (ORR)
ORR is defined as the proportion of participants in the analysis population who have a complete or partial response (CR or PR) using RANO 2.0 criteria. CR is defined as the disappearance of all enhancing measurable and non-measurable disease sustained for at least 4 weeks, no new lesions, stable or better clinical status, and no corticosteroid use. PR is defined as 50% or more decrease in the in sum of the products of perpendicular diameters of all lesions or 65% or more decrease in total volume of all measurable enhancing lesions compared with baseline, sustained for at least 4 weeks, no new lesions, no progression of non-measurable enhancing disease or non-target lesions, corticosteroid dose should be the same or lower compared to baseline, and clinical status should be stable or better compared to baseline.
Measured: 4 years
Duration of response (DOR)
DOR is defined as the time that criteria for CR or PR (whichever is recorded first) is met until the date that recurrent or PD is objectively documented or expiration. RANO 2.0 will be used to assess response. PD is defined above for PFS at 6 months. CR and PR are defined above for ORR.
Measured: 4 years
Incidence of Adverse Events (AEs)
An AE is defined as any untoward medical occurrence associated with the use of an intervention in humans, whether or not considered to be intervention-related. AEs will be documented from the time that the informed consent form is signed to the end of participation on the study. The number of total AEs will be calculated for this outcome.
Measured: 4 years
Incidence of Serious Adverse Events (SAEs)
An SAE is defined as an AE that results in any of the following outcomes:
- Death
- Life-threatening adverse event
- Inpatient hospitalization or prolongation of existing hospitalization
- Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions
- Congenital anomaly/birth defect
Important medical events that may not result in death, be life-threatening, or require hospitalization may be considered an SAE when, based upon appropriate medical judgment, they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
SAEs will be documented from the time that the informed consent form is signed to the end of participation on the study. The number of total SAEs will be calculated for this outcome.
Measured: 4 years
Mortality
Number of participants who expire while on study.
Measured: 4 years
Incidence of laboratory abnormalities
Laboratory values that fall outside the normal range will be documented, whether or not the values are considered clinically significant. The number of total laboratory abnormalities will be calculated for this outcome.
Note: clinically significant laboratory abnormalities also will be documented as adverse events.
Measured: 4 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2025
- Study start3 Dec 2025
- Primary completionDec 2030 (estimated)
- Study completionDec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for GlioblastomaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 190 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Baptist Health South Florida
- Sponsor type
- University, hospital or other
- Collaborators
- Incyte Corporation
- Responsible party
- Sponsor
- Investigators
- Manmeet Ahluwalia, M.D., MBA, Principal investigator, Baptist Health Herbert Wertheim Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06991101
- Sponsor's protocol ID
- 2023-AHL-001
- Status last verified
- Sep 2026
- First submitted
- 19 May 2025
- Last updated
- 2 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Miller KD, Ostrom QT, Kruchko C, Patil N, Tihan T, Cioffi G, Fuchs HE, Waite KA, Jemal A, Siegel RL, Barnholtz-Sloan JS. Brain and other central nervous system tumor statistics, 2021. CA Cancer J Clin. 2021 Sep;71(5):381-406. doi: 10.3322/caac.21693. Epub 2021 Aug 24.
PubMed 34427324Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005 Mar 10;352(10):987-96. doi: 10.1056/NEJMoa043330.
PubMed 15758009Cao Y, Lathia JD, Eyler CE, Wu Q, Li Z, Wang H, McLendon RE, Hjelmeland AB, Rich JN. Erythropoietin Receptor Signaling Through STAT3 Is Required For Glioma Stem Cell Maintenance. Genes Cancer. 2010 Jan 1;1(1):50-61. doi: 10.1177/1947601909356352.
PubMed 20657792Guryanova OA, Wu Q, Cheng L, Lathia JD, Huang Z, Yang J, MacSwords J, Eyler CE, McLendon RE, Heddleston JM, Shou W, Hambardzumyan D, Lee J, Hjelmeland AB, Sloan AE, Bredel M, Stark GR, Rich JN, Bao S. Nonreceptor tyrosine kinase BMX maintains self-renewal and tumorigenic potential of glioblastoma stem cells by activating STAT3. Cancer Cell. 2011 Apr 12;19(4):498-511. doi: 10.1016/j.ccr.2011.03.004.
PubMed 21481791Becker H, Engelhardt M, von Bubnoff N, Wasch R. Ruxolitinib. Recent Results Cancer Res. 2014;201:249-57. doi: 10.1007/978-3-642-54490-3_16.
PubMed 24756798