Navitoclax + Ruxolitinib for Myelofibrosis

(TRANSFORM-1 Trial)

No longer recruiting at 321 trial locations

Overseen By ABBVIE CALL CENTER

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: AbbVie

Must be taking: Ruxolitinib

Must not be taking: JAK-2 inhibitors, BH3-mimetics

Disqualifiers: Stem cell transplant, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 96 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether combining navitoclax and ruxolitinib can better manage myelofibrosis, a type of bone marrow cancer. Myelofibrosis often causes severe fatigue due to anemia and an enlarged spleen. Participants will be divided into two groups: one will receive both drugs, while the other will receive ruxolitinib with a placebo (a pill with no active drug). The trial seeks adults with myelofibrosis who struggle with symptoms like an enlarged spleen and are ineligible for stem cell transplants. Participants must attend regular hospital or clinic visits for assessments and tests. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

You may need to stop taking medications that interfere with blood clotting or platelet function, except for low-dose aspirin and certain blood thinners. The trial does not specify other medication restrictions, so it's best to discuss your current medications with the study team.

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

Research has shown that the combination of navitoclax and ruxolitinib has been studied for its safety and effects on patients with myelofibrosis. In one study, this combination was generally well-tolerated. Some patients experienced a decrease in platelet levels, which are cells that help with blood clotting, but researchers closely monitored this.

Another study found that the combination led to noticeable reductions in spleen size and improvements in anemia without causing severe side effects. These findings suggest that navitoclax and ruxolitinib together have a manageable safety profile, meaning they do not cause many serious problems for most patients.

Participants must attend regular check-ups during the trial to monitor any side effects and ensure the treatment works as expected. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for myelofibrosis?

Researchers are excited about Navitoclax combined with Ruxolitinib for treating myelofibrosis because it targets the disease in a new way. While standard treatments often focus on controlling symptoms, Navitoclax works by inhibiting BCL-2 family proteins, which are involved in the survival of cancer cells. This combination could potentially enhance the effectiveness of Ruxolitinib, a JAK inhibitor that is already a standard treatment, by directly impacting the underlying cell mechanisms of the disease. This unique dual approach might lead to better control of the disease and improved patient outcomes.

What evidence suggests that this trial's treatments could be effective for myelofibrosis?

In this trial, participants will receive either the combination of Navitoclax and Ruxolitinib or a placebo for Navitoclax alongside Ruxolitinib. Research has shown that adding Navitoclax to Ruxolitinib can help reduce spleen size in patients with myelofibrosis. Earlier studies demonstrated lasting effects from this combination, suggesting that the benefits continue over time and may also slow disease progression. Navitoclax blocks proteins that help cancer cells survive, making it a good partner for Ruxolitinib. Ruxolitinib alone has effectively reduced spleen size and symptoms, providing relief for many patients. Together, these drugs might offer a stronger and longer-lasting benefit for people with myelofibrosis. ^{2 3 5 6 7}

Who Is on the Research Team?

ABBVIE INC.

Principal Investigator

AbbVie

Are You a Good Fit for This Trial?

Adults with myelofibrosis, a bone marrow cancer causing anemia and enlarged spleen. Participants must have certain levels of disease severity and symptoms, be able to complete symptom assessments, and not be eligible for stem cell transplantation due to various reasons.

Inclusion Criteria

My spleen is enlarged, confirmed by a scan.

My myelofibrosis is classified as intermediate-2 or high-risk.

Must be able to complete the MF Symptom Assessment Form (MFSAF) v4.0 on at least 4 out of 7 days immediately preceding the date of randomization

Exclusion Criteria

I am not on blood thinners, except for low dose aspirin or LMWH.

I have previously been treated with specific cancer drugs or had a stem cell transplant.

I have been treated with a JAK-2 inhibitor before.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive oral navitoclax tablet with oral ruxolitinib tablet or oral ruxolitinib tablet with oral placebo tablet. Treatment continues until intolerance, lack of benefit, or other discontinuation criteria are met.

Up to 96 weeks

Regular visits at a hospital or clinic

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessments of spleen volume reduction and symptom scores.

Up to 8 years

What Are the Treatments Tested in This Trial?

Interventions

• Navitoclax
• Placebo for Navitoclax
• Ruxolitinib

Trial Overview The trial is testing if taking Navitoclax tablets along with Ruxolitinib is better than just Ruxolitinib for reducing spleen size in myelofibrosis patients. It's a global study involving around 230 participants who will receive treatments orally.

How Is the Trial Designed?

Group I: Navitoclax + Ruxolitinib Experimental Treatment 2 Interventions

Participants will receive Navitoclax in combination with Ruxolitinib

Group II: Placebo for Navitoclax + Ruxolitinib Active Control 2 Interventions

Participants will receive placebo for Navitoclax and Ruxolitinib

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

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2950328024000566

Addition of navitoclax to ruxolitinib for patients with ... Adding navitoclax to ongoing ruxolitinib demonstrates durable responses and potential disease modification in relapsed/refractory MF.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9113204/

Addition of Navitoclax to Ongoing Ruxolitinib Therapy for ... This phase II trial investigated the efficacy and safety of adding BCL-X L /BCL-2 inhibitor navitoclax to ruxolitinib therapy in patients with myelofibrosis

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03222609

NCT03222609 | A Study Evaluating Tolerability and ... Completed. A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis (REFINE).

4. ashpublications.org ashpublications.org/ashclinicalnews/news/8663/Is-Combination-Therapy-Warranted-in-Myelofibrosis

Is Combination Therapy Warranted in Myelofibrosis? In the clinical trial setting, ruxolitinib significantly reduced spleen size and symptoms compared with the best available therapy.

5. ascopubs.org ascopubs.org/doi/10.1200/JCO.2022.40.16_suppl.7015

Navitoclax plus ruxolitinib in JAK inhibitor-naive patients ... Key secondary endpoints were ≥50% reduction in total symptom score (TSS50), bone marrow (BM) fibrosis reduction, and anemia response. Adverse ...

6. ashpublications.org ashpublications.org/bloodneoplasia/article/2/1/100056/525855/Addition-of-navitoclax-to-ruxolitinib-for-patients

Addition of navitoclax to ruxolitinib for patients with ... REFINE is, to our knowledge, the first clinical trial examining the efficacy and safety of adding navitoclax to ruxolitinib for patients with ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT04041050

NCT04041050 | A Study Evaluating Safety and Tolerability ... A Phase 1 Open-Label Study Evaluating the Safety and Tolerability, and Pharmacokinetics of Navitoclax Monotherapy and in Combination With Ruxolitinib in ...