Navitoclax + Ruxolitinib for Myelofibrosis

(REFINE Trial)

Recruiting at 183 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: AbbVie

Must be taking: Ruxolitinib

Must not be taking: Coagulation inhibitors, CYP3A inhibitors

Disqualifiers: Splenectomy, Leukemic transformation, 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

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

191 Participants Needed

Trial Summary

What is the purpose of this trial?

This is a Phase 2 open-label, multicenter study evaluating tolerability and efficacy of navitoclax alone or when added to ruxolitinib in participants with myelofibrosis. Safety and efficacy data through 16 January 2023 are included in the interim analysis.

Research Team

ABBVIE INC.

Principal Investigator

AbbVie

Eligibility Criteria

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

I have been diagnosed with a high-risk form of Myelofibrosis.

I cannot or do not want to have a stem cell transplant due to my age, health issues, or personal choice.

I can take care of myself and am up and about more than half of my waking hours.

Exclusion Criteria

I haven't taken strong or moderate CYP3A inhibitors in the last 14 days.

I am not on blood thinners, except for low dose aspirin or low-molecular-weight heparin.

I have previously received treatment with a BH3 mimetic or had a stem cell transplant.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive navitoclax alone or in combination with ruxolitinib, with dose adjustments based on platelet count and treatment response

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 254 weeks

Open-label extension (optional)

Participants may continue treatment until end of clinical benefit or unacceptable toxicity

Treatment Details

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.

Participant Groups

Group I: Navitoclax + ruxolitinib (Cohort 3) Experimental Treatment 2 Interventions

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 will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).

Group II: Navitoclax + ruxolitinib (Cohort 1b) Experimental Treatment 2 Interventions

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 will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).

Group III: Navitoclax + ruxolitinib (Cohort 1a) Experimental Treatment 2 Interventions

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 will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).

Group IV: Navitoclax (Cohort 2) Experimental Treatment 1 Intervention

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 will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).

Who Is Running the Clinical Trial?

AbbVie

Lead 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