Ruxolitinib + Venetoclax for Acute Myeloid Leukemia

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Jennifer Saultz

Must not be taking: CYP3A inhibitors, CYP3A inducers

Disqualifiers: Acute promyelocytic leukemia, CNS involvement, others

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

Compensation: Varies

Number of Visits: 7

51 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine the optimal dose and assess the safety of combining ruxolitinib (a JAK inhibitor) and venetoclax (a BCL-2 inhibitor), compared to adding azacitidine, for treating acute myeloid leukemia (AML) that has relapsed or not responded to previous treatments. Ruxolitinib and venetoclax block proteins that aid cancer cell growth and survival, while azacitidine prevents cancer cells from making DNA, potentially killing them. The trial seeks participants with AML that has returned or not responded to treatment, especially those who have tried other therapies. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering a chance to be among the first to receive this new combination therapy.

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

The trial protocol does not specify if you must stop taking your current medications, but it mentions that you cannot use medications that interact with the study drugs unless they can be adjusted or stopped. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

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

Research has shown that the combination of ruxolitinib and venetoclax is generally well-tolerated by patients with relapsed or refractory acute myeloid leukemia (AML). One study found that this combination did not cause severe side effects that would prevent dosage increases and demonstrated a promising response rate during initial treatment cycles. Patients handled the drugs well without experiencing serious side effects.

For the combination of ruxolitinib, venetoclax, and azacitidine, research suggests this mix is both effective and safe. Azacitidine, when used with venetoclax, has been shown to be safe for both newly diagnosed and relapsed AML patients, which is reassuring for those considering joining the trial. These results suggest that the treatments might be safe to try, but as with any medical study, individual experiences can vary. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the combination of ruxolitinib and venetoclax for treating acute myeloid leukemia (AML) because it offers a potentially more effective approach by targeting cancer cell survival pathways differently than traditional chemotherapy. Ruxolitinib is a JAK1/2 inhibitor that disrupts key signaling pathways that cancer cells use to grow, while venetoclax works by inhibiting BCL-2, a protein that helps cancer cells avoid death. This dual approach is thought to enhance treatment effectiveness compared to the standard options, which typically include chemotherapy agents like cytarabine and daunorubicin. The addition of azacitidine in one arm further differentiates this treatment by incorporating a DNA methyltransferase inhibitor, which may help reprogram cancer cells to die. This combination could lead to better outcomes for AML patients who have limited treatment options.

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

Research has shown that combining the drugs ruxolitinib and venetoclax may help treat acute myeloid leukemia (AML) that has returned or is difficult to treat. In one study, 63% of patients benefited from this combination, suggesting it could assist many patients during the initial treatment cycles. In this trial, one group of participants will receive this combination. Another group will receive a combination of ruxolitinib, venetoclax, and azacitidine, which has been found effective and safe for both new and recurring AML cases. This combination has demonstrated lasting effects, meaning the benefits continue over time. Both treatment combinations are under study for their potential to improve outcomes in difficult-to-treat AML. ^{1 4 5 6 7}

Who Is on the Research Team?

Jennifer N. Saultz, MD

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

Adults with relapsed or refractory acute myeloid leukemia (AML) who've had at least one prior treatment can join this trial. They must be able to take oral meds, have a certain level of organ function, and not be pregnant or breastfeeding. Contraception is required for participants of childbearing potential.

Inclusion Criteria

Creatinine clearance >= 30 mL/min; calculated by the Cockcroft Gault formula or measured by 24 hours urine collection

Total serum bilirubin =< 1.5 x upper limit of normal (ULN) unless thought to be due to leukemic involvement

Serum aspartate transaminase (AST) and/or alanine transaminase (ALT) =< 3.0 x ULN unless thought to be due to leukemic involvement

Exclusion Criteria

Diagnosis of acute promyelocytic leukemia (APL, or AML M3 subtype)

Clinically significant graft versus host disease (GVHD) or active GVHD requiring initiation or escalation of treatment within 28 day screening period

Participants with rapidly progressive disease (defined by blast count doubles within 48 hours) or organ dysfunction

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment (Arm 1)

Patients receive ruxolitinib and venetoclax orally on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 cycles.

8 weeks

Multiple visits for drug administration and monitoring

Treatment (Arm 2)

Patients receive ruxolitinib, venetoclax, and azacitidine on days 1-7 of each cycle. Cycles repeat every 28 days for up to 2 years.

Up to 2 years

Multiple visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment completion

Every 6 months for up to 2 years

Follow-up visits every 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Ruxolitinib
• Venetoclax

Trial Overview The trial tests the combination of ruxolitinib and venetoclax in AML patients whose disease has returned or resisted treatment. It aims to find the safest doses and see if these drugs are more effective than standard chemotherapy.

How Is the Trial Designed?

Group I: Arm 2 (ruxolitinib,venetoclax, azacitidine) Experimental Treatment 9 Interventions

Patients receive ruxolitinib PO BID, venetoclax PO QD, and azacitidine IV or SC on days 1-7 of each cycle. Cycles repeat every 28 days for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO at screening and blood sample collection and bone marrow aspiration and biopsy throughout the study.

Group II: Arm 1 (ruxolitinib, venetoclax) Experimental Treatment 8 Interventions

Patients receive ruxolitinib PO BID and venetoclax PO QD on days 1-28 of each cycle. Cycles repeat every 28 days for up to 2 cycles in the absence of disease progression or unacceptable toxicity. Patients may receive additional cycles of ruxolitinib and venetoclax at the discretion of the sponsor-investigator. Patients also undergo a skin punch biopsy and ECHO at screening and blood sample collection and bone marrow aspiration and biopsy throughout the study. (COMPLETE 04/04/2025)

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?

Jennifer Saultz

Lead Sponsor

Brian Druker

Lead Sponsor

Trials

1

Recruited

50+

AbbVie

Industry Sponsor

Trials

1,079

Recruited

535,000+

Founded

2013

Headquarters

North Chicago, USA

Known For

Immunology treatments

Top Products

Humira (adalimumab), Skyrizi (risankizumab), Rinvoq (upadacitinib)

Dr. Roopal Thakkar

AbbVie

Chief Medical Officer since 2023

MD from Wayne State University School of Medicine

Robert A. Michael

AbbVie

Chief Executive Officer

Bachelor's degree in Finance from the University of Illinois

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

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Citations

1. 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 ... A Phase 1 trial testing the novel combination therapy of Venetoclax and Ruxolitinib in relapsed/refractory acute myeloid leukemia patients.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10625347/

Potent Personalized Venetoclax Partners for Acute Myeloid ... Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: results from a Phase Ib/II Study.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0006497123081181

Results of a Phase 1 Trial Testing the Novel Combination ... The novel, all-oral combination of Rux+Ven in R/R AML patients was well-tolerated with no DLTs and an encouraging 63% CBR over cycles 1-2.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6168939/

a promising therapeutic strategy for acute myeloid leukemia The combination of venetoclax plus a hypomethylating agent has been reported as an emerging therapeutic strategy for elderly, treatment-naive ...

5. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/216760

Ruxolitinib in Combination With Venetoclax With and ... Giving ruxolitinib in combination with venetoclax and azacitidine may be safe, tolerable, and/or effective compare to ruxolitinib with ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12350645/

Comprehensive view on chemotherapy-free management ... Moreover, duration of response was similar in patients receiving VEN for 14 days (8.7 months, 95% CI 1–37) vs 28 days (8.3 months, 95% CI 1–5, P ...

7. clinicaltrial.be clinicaltrial.be/en/details/5686?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Ruxolitinib in Combination With Venetoclax With and Witho... The QOL summary statistics from each survey will be compared to other studies conducted in relapsed/refractory acute myeloid leukemia patients.