Ruxolitinib + Chemotherapy for Leukemia

Not currently recruiting at 149 trial locations

Overseen By Incyte Corporation Call Center

Age: < 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Incyte Corporation

Disqualifiers: Down syndrome, Ph+ ALL, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new combination treatment for B-cell acute lymphoblastic leukemia (ALL) using ruxolitinib, a JAK inhibitor, with standard chemotherapy. The researchers aim to evaluate the effectiveness of this combination and determine the optimal dose of ruxolitinib. The trial seeks children and young adults up to 21 years old with a high-risk type of ALL called Ph-like B-ALL, particularly those with specific genetic changes who have completed initial treatment. This trial suits individuals with certain genetic markers and a history of frequent white blood cell issues. Participants should not have received other treatments before their initial chemotherapy. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that ruxolitinib is generally well-tolerated by patients. Various studies did not find a pattern of worsening severe anemia or low platelet count with long-term use. One study found that common side effects included low hemoglobin levels, affecting about 2-3% of patients. This indicates that while some side effects can occur, they are usually manageable. Ruxolitinib is also approved for other conditions, suggesting a proven safety record. ^{1 2 3 4 5}

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

Unlike the standard chemotherapy treatments for leukemia, Ruxolitinib offers a unique approach by specifically targeting the JAK-STAT signaling pathway, which is often overactive in blood cancers. This selective action not only aims to reduce cancer cell growth more effectively but also has the potential to spare healthy cells, possibly leading to fewer side effects compared to traditional chemotherapy. Researchers are particularly excited about Ruxolitinib because it might enhance the efficacy of existing chemotherapy regimens, offering hope for better outcomes in patients who may not respond well to current treatments.

What evidence suggests that ruxolitinib in combination with chemotherapy could be an effective treatment for leukemia?

Research has shown that combining ruxolitinib with chemotherapy, the treatment approach tested in this trial, may help treat B-cell acute lymphoblastic leukemia. One study found that this combination helped 20% of patients reach a point where no leukemia cells could be detected. Ruxolitinib is generally well-tolerated, with only a few patients experiencing serious side effects. It works by blocking certain pathways that are often overactive in cancer cells, helping to slow or stop their growth. These findings suggest that using ruxolitinib with chemotherapy could be a promising approach for treating this type of leukemia. ^{3 5 6 7 8}

Who Is on the Research Team?

Sarah Tasian, MD

Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, PA

Albert Assad, MD

Principal Investigator

Incyte Corporation

Are You a Good Fit for This Trial?

This trial is for children and young adults aged 1 to 21 with high-risk B-cell acute lymphoblastic leukemia that shows a specific genetic profile. Participants must have completed initial chemotherapy, not be pregnant or fathering a child, and cannot have certain other health conditions like Down syndrome or active hepatitis.

Inclusion Criteria

I finished a 4-drug treatment and had a test for remaining cancer cells.

I am not able to have children or I agree to use birth control during the study.

I am between 2 and 21 years old and live in Canada.

Exclusion Criteria

My kidney function, measured by creatinine clearance, is below 70 mL/min.

I have Down syndrome.

My leukemia is BCR-ABL1 positive.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Optimization

Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen

8 weeks

Treatment

Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1

12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study tests Ruxolitinib combined with standard chemotherapy in two parts: first finding the best dose of Ruxolitinib, then checking how well it works at that dose. It's for kids who've just been diagnosed and haven't had much treatment yet.

How Is the Trial Designed?

Group I: Ruxolitinib in combination with chemotherapy Experimental Treatment 13 Interventions

Ruxolitinib is already approved in United States, European Union for the following indications:

Approved in United States as Jakafi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Vitiligo

Approved in European Union as Jakavi for:

• Intermediate or high-risk myelofibrosis
• Polycythemia vera
• Steroid-refractory acute graft-versus-host disease
• Chronic graft-versus-host disease
• Non-segmental vitiligo

Who Is Running the Clinical Trial?

Incyte Corporation

Lead Sponsor

Trials

408

Recruited

66,800+

Steven Stein

Incyte Corporation

Chief Medical Officer since 2015

MD from University of Witwatersrand

Hervé Hoppenot

Incyte Corporation

Chief Executive Officer since 2014

MBA from ESSEC Business School

Children's Oncology Group

Collaborator

Trials

467

Recruited

241,000+

Published Research Related to This Trial

In a 3-year follow-up of the COMFORT-II Trial involving 219 patients with myelofibrosis, ruxolitinib demonstrated sustained reductions in spleen size and improved quality of life, with 45% of patients remaining on treatment after 3 years.

Ruxolitinib was well tolerated, with manageable side effects like anemia and thrombocytopenia, and it was associated with longer overall survival compared to the best available therapy, indicating its efficacy and safety as a treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Three-year efficacy, safety, and survival findings from COMFORT-II, a phase 3 study comparing ruxolitinib with best available therapy for myelofibrosis. Cervantes, F., Vannucchi, AM., Kiladjian, JJ., et al.[2022]

Ruxolitinib, an oral JAK1/2 inhibitor, is effective in reducing spleen size and symptom burden in patients with intermediate and high-risk myelofibrosis, making it a valuable treatment option before hematopoietic stem cell transplantation (HSCT).

The impact of ruxolitinib on HSCT outcomes is not well understood, and there is significant variability in how it is used in patients transitioning to HSCT, highlighting the need for more research to guide treatment protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritransplantation Use of Ruxolitinib in Myelofibrosis. Ibrahim, U., Petrone, GEM., Mascarenhas, J., et al.[2021]

Ruxolitinib is strongly recommended for patients with myelofibrosis to improve severe splenomegaly and systemic symptoms, particularly in those with specific risk scores and symptoms like severe itching or unexplained weight loss.

However, there is weak evidence supporting the use of ruxolitinib for improving survival, and these recommendations do not apply to patients eligible for allogeneic stem cell transplant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. Marchetti, M., Barosi, G., Cervantes, F., et al.[2021]

Ruxolitinib, a JAK1/2 inhibitor, provides rapid and significant relief for myelofibrosis patients by reducing spleen size and improving symptoms, but it does not address the underlying bone marrow fibrosis or mutant allele burden, and patients may develop resistance over time.

Other JAK inhibitors like fedratinib, pacritinib, and momelotinib show promise for patients who do not respond well to ruxolitinib, and novel treatments targeting anemia are also being explored, indicating a growing landscape of options for managing myelofibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in potential treatment options for myeloproliferative neoplasm associated myelofibrosis. Bose, P.[2023]

Ruxolitinib is the first targeted therapy approved for treating high- or intermediate-risk myelofibrosis, specifically addressing symptoms like splenomegaly, which is an enlarged spleen.

The authors emphasize the need for pharmacobiological assessments and understanding the risk profile of ruxolitinib in myeloproliferative neoplasms (MPNs) to optimize its clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacobiological Approach for the Clinical Development of Ruxolitinib in Myeloproliferative Neoplasms. Eliaçık, E., Işık, A., Aksu, S., et al.[2021]

Ruxolitinib, a JAK-2 inhibitor used for treating myeloproliferative neoplasms, is generally associated with very rare skin toxicity, but an unusual case of erythematous skin eruption with necrotic centers was observed in a patient with primary myelofibrosis.

This case highlights the need for increased awareness of potential skin side effects from ruxolitinib, especially as JAK-2 inhibitors may be used more widely in dermatological treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Erythematous skin lesions with necrotic centers on lower extremities due to the use of ruxolitinib for primary myelofibrosis. Dasanu, CA.[2021]

Ruxolitinib is a dual inhibitor of JAK1 and JAK2, which are crucial in the development of myelofibrosis (MF), and it has been FDA-approved since November 2011 for treating intermediate or high-risk MF.

The review discusses Ruxolitinib's current role in managing MF and explores its potential future applications in treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. Malhotra, H.[2021]

Ruxolitinib is an effective treatment for patients with polycythaemia vera (PV) who do not respond well to hydroxyurea, showing superior results in reducing hematocrit and spleen size after 32 weeks in the phase III RESPONSE trial.

The drug is generally well tolerated, with manageable side effects like mild to moderate anemia and thrombocytopenia, making it a valuable option for PV patients with limited treatment alternatives.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: A Review in Polycythaemia Vera. McKeage, K.[2021]

Ruxolitinib is an effective JAK2 inhibitor used to treat myelofibrosis and polycythemia vera, but it carries risks of immunosuppression and increased chances of skin cancer.

An 80-year-old woman treated with ruxolitinib experienced unusual neurological symptoms, including weakness and hypoesthesia in her right arm and leg, highlighting the need for monitoring neurological side effects in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Unexpected Neurological Symptoms of Ruxolitinib: A Case Report. Furia, F., Canevini, MP., Federici, AB., et al.[2023]

In a phase II study, ruxolitinib, starting at a low dose of 5 mg twice daily, showed significant efficacy in myelofibrosis patients with low platelet counts (50-100 × 10^9/L), with 62% of patients achieving stable doses of 10 mg twice daily by week 24, and median reductions in spleen volume and symptoms of 24.2% and 43.8%, respectively.

While some patients experienced thrombocytopenia requiring dose adjustments, the treatment was generally manageable, with mean hemoglobin levels remaining stable, indicating that ruxolitinib can be safely administered to this subset of patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. Talpaz, M., Paquette, R., Afrin, L., et al.[2021]

Ruxolitinib, a JAK1/2 inhibitor recently approved for Myelofibrosis, significantly reduces nitric oxide production and pro-inflammatory cytokines in response to lipopolysaccharide (LPS) stimulation in RAW 264.7 cells, indicating its potential anti-inflammatory effects.

In an endotoxemia model with C57 mice, ruxolitinib improved survival rates by 70% and decreased serum levels of pro-inflammatory cytokines, suggesting it may be a promising therapeutic candidate for sepsis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib protects lipopolysaccharide (LPS)-induced sepsis through inhibition of nitric oxide production in mice. Li, L., He, X., Wang, X., et al.[2022]

Ruxolitinib, a selective JAK1 and JAK2 inhibitor, has shown significant efficacy in treating myelofibrosis, with phase II and III trials demonstrating substantial reductions in spleen size and improvements in symptoms and quality of life for patients.

In phase III studies, ruxolitinib recipients achieved a spleen volume reduction of ≥35% at week 24 compared to placebo (41.9% vs. 0.7%) and best available therapy (31.9% vs. 0%), while also showing longer overall survival, although it requires close monitoring due to potential serious side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib for the treatment of myelofibrosis: its clinical potential. Ostojic, A., Vrhovac, R., Verstovsek, S.[2021]

Ruxolitinib, the first JAK2 inhibitor, has significantly improved symptoms, spleen size, and overall survival in patients with myelofibrosis compared to traditional chemotherapy, but about 50% of patients discontinue it after 3 years due to resistance or intolerance.

While second-generation tyrosine kinase inhibitors have been tested for patients who discontinue ruxolitinib, they have not shown significant effects on disease progression, highlighting the need for new treatments that target different pathways.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel therapeutic agents for myelofibrosis after failure or suboptimal response to JAK2 inhbitors. Breccia, M., Assanto, GM., Laganà, A., et al.[2023]

Ruxolitinib is an effective oral treatment for myelofibrosis, showing significant and lasting improvements in symptoms and splenomegaly in patients from major clinical trials, including the phase III COMFORT-I and -II studies with a survival advantage for those treated with ruxolitinib.

While ruxolitinib can cause dose-related anemia and thrombocytopenia, these side effects are manageable and rarely lead to treatment discontinuation, highlighting the importance of monitoring and dosage adjustments for optimal patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib: a review of its use in patients with myelofibrosis. Plosker, GL.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4081383/

Phase 2 study of the JAK kinase inhibitor ruxolitinib in ... Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single ...

2. acsjournals.onlinelibrary.wiley.com acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35661

Ten years of experience with ruxolitinib since approval for ... This study reviews the safety and efficacy profile of the oral JAK1/2 inhibitor ruxolitinib from the decade since its 2014 Food and Drug ...

3. ashpublications.org ashpublications.org/blood/article/142/Supplement%201/1515/498895/Results-of-a-Phase-1-Trial-Testing-the-Novel

Results of a Phase 1 Trial Testing the Novel Combination ... Morphologic leukemia-free state (MLFS) was achieved in 20% (95% CI: 8%-39%) and Composite Complete Remission in 10% (95% CI: 2%-27%).

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7106977/

Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic ... Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring CSF3R-T618I were most ...

5. jhoonline.biomedcentral.com jhoonline.biomedcentral.com/articles/10.1186/s13045-023-01471-z

Ten years of treatment with ruxolitinib for myelofibrosis Ruxolitinib has been shown to not only improve splenomegaly and the burdensome symptoms associated with MF but also to improve overall survival (OS).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4380721/

Efficacy, safety, and survival with ruxolitinib in patients with ... Ruxolitinib continued to be generally well tolerated; there was no pattern of worsening grade ≥3 anemia or thrombocytopenia with longer-term ruxolitinib ...

7. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/1101/491958/Efficacy-and-Safety-of-Ruxolitinib-for-Treatment

Efficacy and Safety of Ruxolitinib for Treatment of Symptomatic ... Collectively, our data suggests that ruxolitinib is a viable therapeutic for patients with symptomatic CMML.

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.6573

Efficacy and safety of ruxolitinib in patients with lower risk ... By week 48, 26 (65.0%) patients achieved a ≥ 50% decrease in palpable spleen length. 32 (80.0%) patients achieved a ≥ 50% reduction from ...