Ruxolitinib + Chemotherapy for Leukemia

Recruiting at 147 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

171 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a nonrandomized study of ruxolitinib in combination with a standard multi-agent chemotherapy regimen for the treatment of B-cell acute lymphoblastic leukemia. Part 1 of the study will optimize the dose of study drug (ruxolitinib) in combination with the chemotherapy regimen. Part 2 will evaluate the efficacy of combination chemotherapy and ruxolitinib at the recommended dose determined in Part 1.

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.

What data supports the effectiveness of the drug Ruxolitinib for leukemia?

Ruxolitinib has shown effectiveness in treating myelofibrosis, a related blood disorder, by reducing spleen size, improving symptoms, and enhancing quality of life. It has also been associated with longer survival in patients compared to other therapies. ^{1 2 3 4 5}

Is Ruxolitinib generally safe for humans?

Ruxolitinib is generally well tolerated in humans, with common side effects including anemia (low red blood cell count) and thrombocytopenia (low platelet count), which are usually manageable. Rare side effects include skin reactions and neurological symptoms like dizziness and headache. It may also increase the risk of infections and skin cancer. ^{1 6 7 8 9}

How is the drug Ruxolitinib unique in treating leukemia?

Ruxolitinib is unique because it is a JAK1 and JAK2 inhibitor, which means it targets specific proteins involved in cell signaling pathways that are often overactive in certain blood cancers. This mechanism is different from traditional chemotherapy, which generally targets rapidly dividing cells without such specificity. ^{10 11 12 13 14}

Research Team

Sarah Tasian, MD

Principal Investigator

Children's Hospital of Philadelphia, Philadelphia, PA

Albert Assad, MD

Principal Investigator

Incyte Corporation

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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, 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]

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 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 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, 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, 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 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, 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]

References

1. United States 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. [2022]

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

Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations. [2021]

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

Novel therapeutic agents for myelofibrosis after failure or suboptimal response to JAK2 inhbitors. [2023]

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

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

5. England pubmed.ncbi.nlm.nih.gov

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

6. Turkey pubmed.ncbi.nlm.nih.gov

Pharmacobiological Approach for the Clinical Development of Ruxolitinib in Myeloproliferative Neoplasms. [2021]

7. Canada pubmed.ncbi.nlm.nih.gov

Unexpected Neurological Symptoms of Ruxolitinib: A Case Report. [2023]

8. England pubmed.ncbi.nlm.nih.gov

Interim analysis of safety and efficacy of ruxolitinib in patients with myelofibrosis and low platelet counts. [2021]

9. England pubmed.ncbi.nlm.nih.gov

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

10. India pubmed.ncbi.nlm.nih.gov

Janus activated kinase inhibition in myelofibrosis. [2021]

11. China pubmed.ncbi.nlm.nih.gov

Ruxolitinib protects lipopolysaccharide (LPS)-induced sepsis through inhibition of nitric oxide production in mice. [2022]

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

Peritransplantation Use of Ruxolitinib in Myelofibrosis. [2021]

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

Ruxolitinib: A Review in Polycythaemia Vera. [2021]

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

Ruxolitinib for the treatment of myelofibrosis: its clinical potential. [2021]