Ruxolitinib + Tyrosine Kinase Inhibitors for Chronic Myeloid Leukemia

Not currently recruiting at 561 trial locations
Age: 18+
Sex: Any
Trial Phase: Phase 2
Sponsor: SWOG Cancer Research Network
Must be taking: Tyrosine kinase inhibitors
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)
Prior Safety DataThis treatment has passed at least one previous human trial

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of different treatments for chronic myeloid leukemia (CML), a type of blood cancer. It examines tyrosine kinase inhibitors, which reduce cancer cells by blocking a necessary protein, and ruxolitinib, a drug that may further aid by blocking growth factors cancer cells use to expand. Participants will either continue their current treatment or add ruxolitinib to assess its additional benefits. This trial suits individuals who have maintained stable CML treatment for at least 12 months and whose CML has not worsened. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you continue taking your current tyrosine kinase inhibitor medication, such as bosutinib, nilotinib, dasatinib, or imatinib, for the duration of the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that ruxolitinib, when combined with other medications like dasatinib or nilotinib, is generally well-tolerated. Past studies found no unexpected safety issues with ruxolitinib. However, some patients experienced lower blood counts, including anemia (low red blood cells) and thrombocytopenia (low platelets), which are the most common side effects.

Dasatinib, nilotinib, and bosutinib are already used to treat chronic myeloid leukemia. These medications work by blocking a protein that aids cancer cell growth. They have been widely used and studied, and their safety is well understood.

Overall, while some side effects may occur, many patients find the treatments manageable. Prospective trial participants should discuss potential risks and benefits with their healthcare provider.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about combining ruxolitinib with tyrosine kinase inhibitors (TKIs) like dasatinib, nilotinib, and imatinib for chronic myeloid leukemia (CML) because of its unique approach. While TKIs are standard for CML, ruxolitinib introduces a new angle by targeting the JAK-STAT pathway, which could help overcome resistance and improve outcomes. This combination might offer enhanced effectiveness compared to traditional TKI treatments alone, potentially leading to better disease control and fewer side effects. By targeting multiple pathways simultaneously, the hope is to achieve a more comprehensive treatment response.

What evidence suggests that this trial's treatments could be effective for chronic myeloid leukemia?

Research has shown that certain drugs, known as tyrosine kinase inhibitors—such as bosutinib, dasatinib, nilotinib, and imatinib—effectively reduce cancer cells in people with chronic myeloid leukemia (CML). These drugs block a protein called BCR-ABL, which aids cancer cell growth. They are commonly used and have successfully treated CML by significantly lowering leukemia cell counts in the body. Participants in this trial may receive one of these tyrosine kinase inhibitors alone.

In another arm of this trial, participants will receive a combination of ruxolitinib and a tyrosine kinase inhibitor. Ruxolitinib targets the growth factors that CML cells need to survive. Early research suggests that adding ruxolitinib to tyrosine kinase inhibitors might better target the bone marrow, where these cancer cells grow, potentially enhancing treatment effectiveness. Although more research is needed, this combination shows promise for improving CML treatment outcomes.26789

Who Is on the Research Team?

KL

Kendra L Sweet

Principal Investigator

SWOG Cancer Research Network

Are You a Good Fit for This Trial?

This trial is for chronic myeloid leukemia patients who've been on tyrosine kinase inhibitors (TKI) like bosutinib, dasatinib, imatinib or nilotinib for at least a year. They should have stable vital signs and organ function, not be pregnant or breastfeeding, agree to use contraception, and not have HIV with detectable viral loads. Prior cancer is okay if no active treatment is needed.

Inclusion Criteria

My BCR-ABL levels are between 0.0032% and 1.0% as confirmed by a recent test.
Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x institutional upper limit of normal (IULN) within 7 days prior to randomization
Total bilirubin =< 1.5 x IULN within 7 days prior to randomization
See 20 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a tyrosine kinase inhibitor alone or in combination with ruxolitinib for up to 12 months, with treatment cycles repeating every 90 days

12 months
4 cycles of 90 days each

Follow-up

Participants are monitored for safety, effectiveness, and survival outcomes after treatment completion

Up to 5 years
Every 6 months for 2 years, then annually

What Are the Treatments Tested in This Trial?

Interventions

  • Bosutinib
  • Dasatinib
  • Imatinib
  • Nilotinib Hydrochloride Monohydrate
  • Ruxolitinib Phosphate
Trial Overview The study tests adding Ruxolitinib—a drug that blocks growth factors necessary for leukemia cells—to the usual TKI treatments. It's a phase II randomized trial aiming to see if this combination better reduces leukemia cell counts compared to TKI alone.
How Is the Trial Designed?
2Treatment groups
Experimental Treatment
Active Control
Group I: Arm II (ruxolitinib phosphate, dasatinib, nilotinib, imatinib)Experimental Treatment5 Interventions
Group II: Arm I (bosutinib, dasatinib, nilotinib, imatinib)Active Control5 Interventions

Bosutinib is already approved in United States for the following indications:

🇺🇸
Approved in United States as Bosulif for:

Find a Clinic Near You

Who Is Running the Clinical Trial?

SWOG Cancer Research Network

Lead Sponsor

Trials
403
Recruited
267,000+

Southwest Oncology Group

Lead Sponsor

Trials
389
Recruited
260,000+

National Cancer Institute (NCI)

Collaborator

Trials
14,080
Recruited
41,180,000+

Published Research Related to This Trial

Bosutinib is an effective treatment for chronic myeloid leukemia, particularly in patients who have developed resistance or intolerance to other tyrosine kinase inhibitors, demonstrating sustained efficacy in the chronic phase of the disease.
The safety profile of bosutinib includes distinct but manageable side effects, and it can be used without absolute contraindications in most patients, except those with specific mutations (T315I and V299L).
Bosutinib: a SRC-ABL tyrosine kinase inhibitor for treatment of chronic myeloid leukemia.Rassi, FE., Khoury, HJ.[2021]
In a cost-effectiveness analysis involving 100 patients with chronic myeloid leukemia, nilotinib was found to provide more progression-free life-years saved (15.21) compared to imatinib (12.64) and dasatinib (14.91), indicating its superior efficacy as a first-line treatment.
Nilotinib was also shown to be more cost-effective than dasatinib, with a lower incremental cost-effectiveness ratio of US$ 33,120.36 per progression-free life-year saved, making it the preferred option for treatment in Colombia.
Cost-effectiveness of nilotinib, dasatinib and imatinib as first-line treatment for chronic myeloid leukemia in Colombia, 2012.Romero, M., Chávez, D., De Los Ríos, M., et al.[2022]
Bosutinib is a newly approved tyrosine kinase inhibitor for chronic myeloid leukemia that is effective even in the presence of most kinase domain mutations, making it a valuable treatment option.
The primary side effects of bosutinib are gastrointestinal issues, which should be considered when selecting it as a treatment in the appropriate clinical setting.
Clinical advances in the management of chronic myelogenous leukemia: focus on bosutinib and patient considerations.Sweet, K., Pinilla-Ibarz, J., Zhang, L.[2021]

Citations

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 ...
2.pubmed.ncbi.nlm.nih.govpubmed.ncbi.nlm.nih.gov/31880950/
Efficacy of Ruxolitinib in Patients With Chronic Neutrophilic ...Conclusion: Ruxolitinib was well tolerated and demonstrated an estimated response rate of 32%. Patients with a diagnosis of CNL and/or harboring ...
S1712 Supports Adding Ruxolitinib to TKIs for CMLPreclinical data suggested that a drug called ruxolitinib can alter the bone marrow microenvironment to sensitize these stem cells to TKIs.
Ruxolitinib Plus Flumatinib Seems Safe and Effective in MF ...Treatment with flumatinib plus ruxolitinib seems safe and effective in patients with primary myelofibrosis (MF) and chronic myelogenous ...
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 ...
Clinical Review - Ruxolitinib (Jakavi) - NCBI - NIHAccording to the clinical experts consulted by CADTH, no unexpected safety concerns were observed with ruxolitinib. Go to: Introduction. Disease Background.
Video | PV Mechanism of Action & Safety DataDr Erba: Twenty-three percent of patients treated with Jakafi achieved the composite endpoint versus only less than 1% of patients on best available therapy.
Ten years of treatment with ruxolitinib for myelofibrosisCytopenias, in particular anemia and thrombocytopenia, are the most frequent adverse events (AEs) with ruxolitinib in patients with MF (Table 1) ...
Ruxolitinib versus Standard Therapy for the Treatment ...A complete hematologic remission was achieved in 24% of patients in the ruxolitinib group and 9% of those in the standard-therapy group (P=0.003); ...
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