Ruxolitinib + Chemotherapy for Acute Lymphoblastic Leukemia

Overseen By Clinical Trials Office

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Chicago

Must be taking: Intrathecal chemotherapy

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Second malignancy, Allergic reactions, Uncontrolled illness, others

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

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

Compensation: Varies

Number of Visits: Unknown

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether adding ruxolitinib, a JAK inhibitor, to standard chemotherapy is safe for individuals with Ph-like acute lymphoblastic leukemia (ALL), a specific type of blood cancer. The focus is on adolescents and young adults recently diagnosed with this condition. Participants must confirm they have a B-precursor type of ALL and a specific genetic marker known as "Ph-like." The study aims to determine if this new treatment combination could improve outcomes for patients facing this challenging form of leukemia. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment combination.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop all current medications, but you cannot take any potent CYP3A4 inhibitors or inducers within 5 half-lives before starting the study drug. It's important to discuss your current medications with the study team to avoid any interactions.

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

Research has shown that ruxolitinib is generally well-tolerated. One study used it with chemotherapy, and most patients managed it well. Only a few experienced serious side effects, such as multi-organ failure, which was very rare, occurring in just one patient.

Other studies have found that ruxolitinib can cause common side effects like nausea and headaches, but these are usually mild. Its safety in treating acute graft-versus-host disease also supports its overall safety. Only a small number of patients experienced serious issues like blood clots.

Overall, while ruxolitinib can cause side effects, they are often manageable. Participants should discuss any concerns with their healthcare provider. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Ruxolitinib is unique because it targets the JAK-STAT pathway, which is crucial in the development and progression of acute lymphoblastic leukemia (ALL). Unlike standard chemotherapy, which broadly attacks rapidly dividing cells, ruxolitinib is a selective JAK inhibitor that may help reduce cancer cell growth more precisely and potentially with fewer side effects. Researchers are excited about this treatment because it offers a more targeted approach, potentially improving outcomes for patients with ALL when combined with conventional chemotherapy regimens.

What evidence suggests that adding ruxolitinib to chemotherapy could be effective for acute lymphoblastic leukemia?

Research has shown that ruxolitinib, a type of medication, may help treat Ph-like acute lymphoblastic leukemia (ALL). In this trial, participants will receive ruxolitinib alongside standard chemotherapy. Studies have examined the combination of ruxolitinib with chemotherapy and found it beneficial when added to standard treatment. Patients who received ruxolitinib with chemotherapy did not experience severe side effects that would prevent its use. This suggests that ruxolitinib might be a safe addition to chemotherapy for people with this type of leukemia. While more information is needed, early results are promising for its effectiveness. ^{4 5 6 7 8}

Who Is on the Research Team?

Wendy Stock, MD

Principal Investigator

University of Chicago

Are You a Good Fit for This Trial?

This trial is for adolescents and young adults aged 18-40 with newly diagnosed Ph-like acute lymphoblastic leukemia (ALL). Participants must have completed a specific chemotherapy regimen, have normal organ function, and agree to use contraception. Excluded are those with other active cancers, certain heart or psychiatric conditions, pregnant or breastfeeding women, and individuals on strong CYP3A4 inhibitors.

Inclusion Criteria

Agreement to use adequate contraception for women of child-bearing potential and men

Ability to understand and sign a written informed consent document

I have been newly diagnosed with a specific type of leukemia (B-precursor ALL).

Exclusion Criteria

Down Syndrome

I haven't taken strong CYP3A4 inhibitors recently.

My leukemia was Ph+ at diagnosis.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Induction Therapy

Participants must have completed a 4-drug induction therapy regimen with intrathecal chemotherapy

4 weeks

Remission Consolidation Therapy

Participants receive remission consolidation therapy as part of the standard chemotherapy regimen

8 weeks

Interim Maintenance

Participants undergo interim maintenance therapy as part of the standard chemotherapy regimen

8 weeks

Delayed Intensification

Participants undergo delayed intensification therapy as part of the standard chemotherapy regimen

8 weeks

Maintenance Therapy

Participants receive maintenance therapy in 12-week courses/84-day cycles lasting 2-3 years

2-3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib

Trial Overview The study tests the safety of adding ruxolitinib to a standard multi-drug chemotherapy regimen in treating Ph-like ALL. The goal is to determine if this combination improves outcomes for patients who fit the trial's criteria.

How Is the Trial Designed?

Group I: Ruxolitinib Experimental Treatment 13 Interventions

Participants will receive ruxolitinib in addition to standard chemotherapy. Standard Chemotherapy Consists of: * Remission consolidation therapy (lasting 8 weeks) * Interim Maintenance (lasting 8 weeks) * Delayed Intensification (lasting 8 weeks * Maintenance Therapy (12 week courses/84 day cycles lasting 2-3 years) Prior to study entry, patients must have completed a 4-drug induction therapy regimen with intrathecal chemotherapy (modified Berlin-Frankfurt-Münster (aBFM) regimen or equivalent) as per the institution standard of care.

Who Is Running the Clinical Trial?

University of Chicago

Lead Sponsor

Trials

1,086

Recruited

844,000+

Incyte Corporation

Industry 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

Published Research Related to This Trial

The combination of ruxolitinib and venetoclax shows a dose-dependent effect on T cell acute lymphoblastic leukemia (T-ALL) but does not improve survival in a xenograft model, leading to increased leukemic infiltration in the central nervous system (CNS).

Adding the CXCR4 inhibitor plerixafor to the treatment regimen enhances survival and reduces clinical symptoms, suggesting that targeting the CXCR4-CXCL12 axis may be necessary for achieving better outcomes in T-ALL therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

CXCR4 allows T cell acute lymphoblastic leukemia to escape from JAK1/2 and BCL2 inhibition through CNS infiltration. Walker, KL., Rinella, SP., Hess, NJ., et al.[2022]

In a study of 8 pediatric B-ALL cases, the JAK inhibitor ruxolitinib significantly reduced peripheral and splenic blast counts, especially in samples with JAK-activating mutations, indicating its potential efficacy in treating high-risk Ph-like acute lymphoblastic leukemia.

The mTOR inhibitor rapamycin effectively controlled leukemia burden in all samples and significantly prolonged survival in xenograft models, suggesting it could be a valuable treatment option for this aggressive leukemia subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting JAK1/2 and mTOR in murine xenograft models of Ph-like acute lymphoblastic leukemia. Maude, SL., Tasian, SK., Vincent, T., et al.[2022]

In a study of 53 myelofibrosis patients treated with a combination of hydroxyurea and ruxolitinib, significant reductions in white blood cell and platelet counts were observed after 48 weeks, indicating effective management of myeloproliferation.

The combination therapy also led to a notable decrease in spleen size, with the rate of spleen response increasing from 14% to 45%, while maintaining a safety profile similar to that of ruxolitinib alone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of ruxolitinib and hydroxyurea combination in patients with hyperproliferative myelofibrosis. Breccia, M., Luciano, L., Pugliese, N., et al.[2021]

In a mouse model of Philadelphia chromosome-positive acute lymphoblastic leukemia, the combination of dasatinib (targeting BCR-ABL kinase) and ruxolitinib (targeting JAK2) led to prolonged survival.

This combined treatment approach also helped prevent resistance to therapy, suggesting a promising strategy for improving outcomes in patients with this type of leukemia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting BCR-ABL and JAK2 in Ph+ ALL. Hantschel, O.[2021]

A study analyzing 126,815 safety reports found that the JAK inhibitors ruxolitinib, tofacitinib, and baricitinib are associated with increased risks of infectious adverse events, particularly viral, fungal, and mycobacterial infections.

Tofacitinib specifically showed a significant association with gastrointestinal perforation events, while no significant increase in major cardiovascular events was observed, indicating a need for careful monitoring of these risks in patients using JAK inhibitors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events associated with JAK inhibitors in 126,815 reports from the WHO pharmacovigilance database. Hoisnard, L., Lebrun-Vignes, B., Maury, S., et al.[2023]

Ruxolitinib, a JAK inhibitor, showed potential efficacy in treating a patient with refractory T-cell acute lymphoblastic leukemia (T-ALL) that had a JAK3 mutation, indicating a promising new treatment avenue for this aggressive cancer.

This case highlights the importance of using molecular markers, like JAK3 mutations, to guide treatment decisions in T-ALL, as traditional chemotherapy alone has a low cure rate of only 25-45%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ruxolitinib is effective in the treatment of a patient with refractory T-ALL. Jaramillo, S., Hennemann, H., Horak, P., et al.[2022]

Ruxolitinib, a Janus kinase inhibitor, showed promising efficacy in treating Philadelphia-like acute lymphoblastic leukemia (Ph-like ALL), with 7 out of 12 patients achieving complete remission and 2 achieving partial remission after treatment.

The study highlights the potential of targeting the JAK-STAT signaling pathway in Ph-like ALL patients, particularly those with specific gene fusions affecting JAK2 and EPOR, suggesting that ruxolitinib could be a valuable addition to standard therapy for this high-risk leukemia subtype.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of ruxolitinib in acute lymphoblastic leukemia: A systematic review. Kołodrubiec, J., Kozłowska, M., Irga-Jaworska, N., et al.[2022]

Ruxolitinib, a treatment for myelofibrosis, has been associated with a case of EBV reactivation leading to a severe lymphoproliferative disorder in a 57-year-old female patient, highlighting a potential risk of opportunistic infections.

This case emphasizes the need for close monitoring of patients on Ruxolitinib for signs of viral reactivations and opportunistic infections, as they may pose serious health risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Case-report: EBV driven lymphoproliferative disorder associated with Ruxolitinib. Pálmason, R., Lindén, O., Richter, J.[2022]

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]

The study demonstrates that targeting the IL-7R pathway with the JAK1/2 inhibitor ruxolitinib effectively induces cell death in T cell acute lymphoblastic leukemia (T-ALL) models, leading to reduced leukemia burden and extended survival in mice.

Combining ruxolitinib with the BCL-2 inhibitor venetoclax shows promise for enhanced therapeutic efficacy, suggesting a potential new treatment strategy for T-ALL that minimizes the toxicity associated with traditional chemotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Inhibiting Janus Kinase 1 and BCL-2 to treat T cell acute lymphoblastic leukemia with IL7-Rα mutations. Senkevitch, E., Li, W., Hixon, JA., et al.[2019]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35939887/

Efficacy of ruxolitinib in acute lymphoblastic leukemia We aimed to investigate the efficacy of target therapy with the Janus kinase inhibitor, ruxolitinib, in patients with Ph-like ALL and molecular signature of ...

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S2152265025001776

A Phase I/II Trial of Ruxolitinib with Chemotherapy for ... We now report the first prospective trial of ruxolitinib or dasatinib added to intensive chemotherapy for patients with relapsed and or refractory Ph-like ALL.

3. ashpublications.org ashpublications.org/blood/article/140/Supplement%201/6117/488039/A-Phase-2-Study-of-Ruxolitinib-with-Chemotherapy

A Phase 2 Study of Ruxolitinib with Chemotherapy in Children ... This clinical trial is investigating the therapeutic potential of the JAK inhibitor ruxolitinib in combination with multi-agent chemotherapy for children, ...

4. clinical-lymphoma-myeloma-leukemia.com clinical-lymphoma-myeloma-leukemia.com/article/S2152-2650(25)00177-6/abstract

A Phase I/II Trial of Ruxolitinib with Chemotherapy for ... We observed no dose-limiting toxicities in the first 2 cohorts of patients receiving ruxolitinib (15 mg BID, n = 5 and 20 mg BID, n = 3), ...

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

Ten years of experience with ruxolitinib since approval for ... This review covers ruxolitinib efficacy and safety data from clinical trials and real-world settings in the decade since ruxolitinib was ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40500616/

A Phase I/II Trial of Ruxolitinib with Chemotherapy for ... We conducted a phase I/II trial to explore the safety and efficacy of ruxolitinib or dasatinib in combination with Hyper-CVAD chemotherapy for patients ≥ 10 ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4546537/

A Phase 1 Dosing Study of Ruxolitinib in Children with ... Ruxolitinib was well-tolerated with one DLT per cohort of 6 patients at dose levels (DLs) 2-5. One patient with a ST had grade 5 multi-organ failure at DL2. One ...

8. hcp.jakafi.com hcp.jakafi.com/acute-graft-versus-host-disease/safety-adverse-events

Safety Profile of Jakafi in aGVHD Safety results for Jakafi ® (ruxolitinib) in REACH1 · Nonhematologic Adverse Reactions Occurring in ≥15% of Patients · Selected Laboratory Abnormalities Worsening ...