Navitoclax + Ruxolitinib for Myelofibrosis
(REFINE Trial)
What You Need to Know Before You Apply
What is the purpose of this trial?
This trial tests the effectiveness of the drugs navitoclax and ruxolitinib (also known as Jakafi, Jakavi, or Opzelura), both individually and in combination, for treating myelofibrosis, a condition affecting the bone marrow and blood cells. The study aims to determine if these drugs can manage symptoms and improve patient outcomes. Individuals diagnosed with myelofibrosis who have tried other treatments, such as ruxolitinib, but still face issues like spleen problems or require frequent blood transfusions, might be suitable candidates for this trial. As a Phase 2 trial, the research focuses on evaluating the treatment's effectiveness in an initial, smaller group of participants.
Will I have to stop taking my current medications?
You may need to stop taking certain medications that interfere with blood clotting or are strong or moderate CYP3A inhibitors before starting the trial. However, you can continue taking low-dose aspirin and low-molecular-weight heparin.
Is there any evidence suggesting that this trial's treatments are likely to be safe?
Research shows that the combination of navitoclax and ruxolitinib is generally well-tolerated by patients with myelofibrosis. Previous studies found these drugs effective even when other treatments failed. However, some patients experienced side effects, with low platelet counts being a common issue. Doctors monitor this closely during treatment.
Navitoclax alone has also been studied and appears safe for most people. Most side effects are not severe and can be managed by adjusting the dose or using other treatments. While most patients taking navitoclax reported some side effects, no new safety concerns emerged. This suggests the treatment is relatively safe, but monitoring for potential issues remains important.12345Why are researchers excited about this trial's treatments?
Researchers are excited about the combination of Navitoclax and Ruxolitinib for treating myelofibrosis because it offers a fresh approach compared to existing therapies like JAK inhibitors. While most current treatments focus solely on inhibiting Janus Kinase (JAK) pathways to reduce symptoms, Navitoclax introduces the unique mechanism of targeting BCL-2 family proteins, which play a role in cell survival. This dual-action, combining JAK inhibition with apoptosis induction, could potentially lead to better control of the disease and improved patient outcomes. Additionally, Navitoclax's ability to be tailored based on individual platelet counts offers a personalized treatment approach, which is a step forward in managing myelofibrosis more effectively.
What evidence suggests that this trial's treatments could be effective for myelofibrosis?
Research has shown that combining the drugs navitoclax and ruxolitinib may be promising for treating myelofibrosis, a type of bone marrow cancer. In this trial, participants in various treatment arms will receive different combinations of these drugs. Studies have found that adding navitoclax to ruxolitinib can significantly reduce spleen size by 35% or more. This combination also improves symptoms and overall health in patients who haven't responded well to previous treatments. While navitoclax alone, tested in a separate arm of this trial, offers some benefits, using it with ruxolitinib appears more effective. Overall, these treatments offer hope for patients with myelofibrosis by potentially slowing the disease's progression.13467
Who Is on the Research Team?
ABBVIE INC.
Principal Investigator
AbbVie
Are You a Good Fit for This Trial?
This trial is for people with myelofibrosis who've been treated with a JAK-2 inhibitor for at least 12 weeks and have significant symptoms or are considered intermediate-2/high-risk. They should be on a stable dose of ruxolitinib if currently taking it, not have had certain prior treatments, and must meet specific health criteria.Inclusion Criteria
Exclusion Criteria
Timeline for a Trial Participant
Screening
Participants are screened for eligibility to participate in the trial
Treatment
Participants receive navitoclax alone or in combination with ruxolitinib, with dose adjustments based on platelet count and treatment response
Follow-up
Participants are monitored for safety and effectiveness after treatment
Open-label extension (optional)
Participants may continue treatment until end of clinical benefit or unacceptable toxicity
What Are the Treatments Tested in This Trial?
Interventions
- Navitoclax
- Ruxolitinib
Trial Overview
The study tests the safety and effectiveness of Navitoclax alone or combined with Ruxolitinib in treating myelofibrosis. It's an open-label Phase 2 trial, meaning both researchers and participants know which treatment is being administered.
How Is the Trial Designed?
4
Treatment groups
Experimental Treatment
Prior treatment with a Janus Kinase 2 (JAK-2) or Bromodomain and Extra-Terminal motif (BET) proteins inhibitor was prohibited. Ruxolitinib tablets administered orally twice daily (BID) based on Baseline platelet count as per the local approved label. Navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (\>150 × 10\^9/L starting dose of 200 mg; ≤150 × 10\^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10\^9/L). Navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose may be increased to 300 mg QD at discretion of Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Those receiving ruxolitinib at Screening must be on a stable dose ≥10 mg tablets orally twice daily (BID) for ≥ 4 weeks prior to 1st dose of navitoclax. Those not receiving ruxolitinib at Screening received 10 mg ruxolitinib BID starting on Day 1. Navitoclax tablets were administered orally once daily (QD) per Baseline platelet count (\>150 × 10\^9/L starting dose of 200 mg; ≤150 × 10\^9/L starting dose of 100 mg, which could be increased to 200 mg QD after 7 days provided platelet count is ≥75 × 10\^9/L). Navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose was increased to 300 mg QD at discretion of the Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Participants must have received ruxolitinib for at least 12 weeks and on stable dose of ≥10 mg tablets orally twice daily (BID) for ≥8 weeks prior to the 1st dose of navitoclax. Navitoclax tablets are administered once daily (QD) at a starting dose of 50 mg. This was increased after approximately ≥7 days to next dose level if platelet count is ≥75 × 10\^9/L up to a maximum dose of navitoclax 300 mg QD. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Participants must have received prior treatment with a Janus Kinase 2 (JAK-2) inhibitor. Those with Baseline platelet count \>150 × 10\^9/L initiated navitoclax film-coated tablets orally once daily (QD) at the starting dose of 200 mg. Those with a Baseline platelet count ≤150 × 10\^9/L initiated navitoclax film-coated tablets orally once daily (QD) at the starting dose of 100 mg, which could be increased to 200 mg once daily after 7 days provided the platelet count is ≥75 × 10\^9/L. Navitoclax didn't exceed 200 mg QD for the first 24 weeks of treatment. After Week 24 disease assessment, navitoclax dose may be increased to 300 mg QD at discretion of the Investigator for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Participants continued their treatment until the end of clinical benefit, unacceptable toxicity, or they met other protocol criteria for discontinuation (whichever occurred first).
Find a Clinic Near You
Who Is Running the Clinical Trial?
AbbVie
Lead Sponsor
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
Citations
Addition of Navitoclax to Ongoing Ruxolitinib Therapy for ...
CONCLUSION. The addition of navitoclax to ruxolitinib in patients with persistent or progressive myelofibrosis resulted in durable SVR35, improved TSS, ...
2.
ashpublications.org
ashpublications.org/bloodneoplasia/article/2/1/100056/525855/Addition-of-navitoclax-to-ruxolitinib-for-patientsAddition of navitoclax to ruxolitinib for patients with ...
Navitoclax plus ruxolitinib demonstrated clinically meaningful efficacy and symptom improvement in patients with R/R MF and suboptimal response ...
NCT03222609 | A Study Evaluating Tolerability and ...
This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of navitoclax alone or when added to ruxolitinib in participants with ...
Navitoclax Monotherapy Mirrors Safety of ...
Notably, at week 24, 7% of patients in cohort 2 achieved a spleen volume reduction of at least 35% (n = 2/29), 10% saw their TSS reduced by at ...
5.
healthtree.org
healthtree.org/myelofibrosis/community/articles/navitoclax-ruxcolitinib-treat-myelofibrosisNavitoclax And Ruxolitinib to Treat Myelofibrosis
ASH 2023 results reveal that a JAK inhibitor combined with navitoclax, a BCL-2 inhibitor showed success in myelofibrosis.
Addition of Navitoclax to Ongoing Ruxolitinib Therapy for ...
TSS50 was achieved by 30% (6 of 20) of patients at week 24, and BMF improved by 1-2 grades in 33% (11 of 33) of evaluable patients. Anemia ...
7.
news.abbvie.com
news.abbvie.com/2022-06-10-AbbVie-Presents-Investigational-Navitoclax-Preliminary-Data-in-JAK-Inhibitor-Naive-Myelofibrosis-PatientsAbbVie Presents Investigational Navitoclax Preliminary ...
Preliminary safety analysis identified no new safety signals. Thirty-one (97 percent) patients reported one or more adverse event (AE).1 The ...
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