Ruxolitinib for Preventing GVHD in Cancer Patients

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: City of Hope Medical Center

Must not be taking: Jak inhibitors

Disqualifiers: Active infection, Uncontrolled illness, MACE, others

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

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether ruxolitinib, a JAK inhibitor, can prevent chronic graft versus host disease (cGVHD) in cancer patients who have undergone a stem cell transplant. cGVHD occurs when donor cells attack the patient's body, causing symptoms like skin rashes, jaundice, or dry eyes. The study examines specific blood markers to predict who might develop cGVHD and uses ruxolitinib to prevent it. It suits patients who have had a stem cell transplant and are at risk for cGVHD. As a Phase 1 trial, this research focuses on understanding how ruxolitinib works in people, offering participants a chance to be among the first to receive this treatment.

Do I have to stop taking my current medications for the trial?

The trial does not specify if you need to stop taking your current medications, but you cannot have used ruxolitinib or other Jak inhibitors in the past 14 days. Prednisone is allowed at a low dose, but other medications for active/progressive GVHD are not permitted.

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

Research has shown that ruxolitinib is generally well-tolerated by patients with graft-versus-host disease (GVHD). In several studies, patients using ruxolitinib experienced positive outcomes. For example, one study found that ruxolitinib was well-tolerated even by patients who had tried many other treatments before. Another study demonstrated that both children and adults benefited from ruxolitinib without major unexpected side effects.

These findings suggest that while ruxolitinib can cause some side effects, they are usually manageable and similar to those observed in earlier studies. Overall, the treatment appears to have a safety profile consistent with previous observations by doctors. ^{1 2 3 4 5}

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

Ruxolitinib is unique because it targets Janus kinase (JAK) pathways, which play a critical role in the immune response involved in graft-versus-host disease (GVHD). Unlike standard treatments that typically involve corticosteroids or calcineurin inhibitors, ruxolitinib specifically inhibits JAK1 and JAK2, potentially reducing inflammation more precisely and with fewer side effects. Researchers are excited about this treatment because it offers a novel mechanism of action that could improve outcomes for cancer patients undergoing hematopoietic cell transplantation (HCT) by preventing or reducing the severity of GVHD.

What evidence suggests that ruxolitinib might be an effective treatment for preventing chronic GVHD?

This trial will compare Ruxolitinib with standard-of-care (SOC) treatment for preventing complications after a stem cell transplant. Studies have shown that Ruxolitinib can effectively prevent problems following a stem cell transplant. In patients treated with Ruxolitinib, two-thirds stopped using corticosteroids, which often manage symptoms. One study found that after two years, 76% of patients were still alive, and 68% experienced no worsening of their disease. For those with severe chronic graft-versus-host disease (GVHD), Ruxolitinib had a response rate of over 78%. This suggests that Ruxolitinib might help prevent or lessen the severity of chronic GVHD, a common issue after a transplant. ^{3 6 7 8 9}

Who Is on the Research Team?

Amandeep Salhotra

Principal Investigator

City of Hope Medical Center

Are You a Good Fit for This Trial?

This trial is for cancer patients aged 18 or older who have had a specific type of bone marrow transplant using donor stem cells. They must be in good health with a Karnofsky performance status ≥ 80, indicating they can carry out normal activities without assistance. Participants need to consent to use their tissue samples and not have received manipulated grafts.

Inclusion Criteria

I am mostly self-sufficient and active.

I have undergone any type of bone marrow preparation treatment.

I am receiving any type of GVHD prevention treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Patients receive ruxolitinib orally twice daily on days 1-28 of each cycle, with cycles repeating every 28 days for up to 12 cycles

12 months

Monthly visits for each cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up visits at 30 days, months 15, 18, and 24, and at the time of cGVHD diagnosis, if applicable

24 months

4 visits (in-person) over 2 years

Long-term follow-up

Participants are monitored for overall survival, quality of life, and incidence of infections up to 2 years post-enrollment

2 years

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study tests if monitoring certain biomarkers after the transplant can predict chronic GVHD, a condition where transplanted cells attack the patient's body. Patients with high biomarker levels will receive Ruxolitinib as prevention, which blocks enzymes involved in developing cGVHD.

How Is the Trial Designed?

Group I: Arm I (ruxolitinib) Experimental Treatment 4 Interventions

Starting between days +105 and +130 post-HCT, patients receive ruxolitinib PO BID on days 1-28 of each cycle. Cycles repeat every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo additional blood sample collection throughout the trial.

Group II: Arm II (SOC treatment) Active Control 4 Interventions

Starting between days +105 and +130 post-HCT, patients receive SOC treatment for up to 1 year in the absence of disease progression or unacceptably toxicity. Patients also undergo additional blood sample collection throughout the trial.

Who Is Running the Clinical Trial?

City of Hope Medical Center

Lead Sponsor

Trials

614

Recruited

1,924,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12283849/

Ruxolitinib treatment outcomes in acute graft-versus-host ... Two-thirds of the patients were able to discontinue CSs, and two-thirds were estimated to be alive at three years from the initiation of ruxolitinib treatment.

2. ashpublications.org ashpublications.org/blood/article/145/20/2312/536227/Low-rates-of-chronic-graft-versus-host-disease

Low rates of chronic graft-versus-host disease with ruxolitinib ... Overall survival and progression-free survival at 2 years were 76% and 68%, respectively. Prolonged administration of ruxolitinib following HCT ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2531137925001038

Long-term follow-up results of ruxolitinib as salvage ... Most patients presented with severe chronic graft-versus-host disease (15/23; 65.2%). The overall response rate was 78.3% (18/23) after a median treatment ...

4. nature.com nature.com/articles/s41392-024-01987-x

Ruxolitinib plus steroids for acute graft versus host disease Ruxolitinib with corticosteroids showed promising efficacy in improving response and failure free survival in our phase I study.

5. haematologica.org haematologica.org/article/view/11990

Lower incidence of chronic graft-<i>versus</i>-host ... The data suggest a better long-term control of aGvHD and less chronic GvHD at one year combining ruxolitinib with ECP compared to ruxolitinib alone in SR-aGvHD.

6. ascopubs.org ascopubs.org/doi/10.1200/JCO-25-00809

Final Analysis From the Randomized Phase III REACH2 Trial Numerically higher chronic GVHD rates were noted with ruxolitinib than with BAT from 12 months; however, 95% confidence intervals overlapped.

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38916742/

Efficacy and safety of ruxolitinib in the treatment of chronic ... Overall, ruxolitinib was relatively well-tolerated and showed outcomes comparable to the REACH3 trial in a heavily pretreated patient population.

8. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.954268/full

Efficacy and safety of ruxolitinib in steroid-refractory graft- ... This study suggests that ruxolitinib is an effective and safe treatment for SR-GVHD, and both children and adults with SR-GVHD could benefit from ruxolitinib ...

9. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/654/503361/Ruxolitinib-in-Patients-With-Chronic-Graft-Versus

Ruxolitinib in Patients With Chronic Graft-Versus-Host ... RUX was well tolerated with no unexpected toxicities and safety that was consistent with earlier studies. Overall, the long-term control of ...