A Study Evaluating Tolerability and Efficacy of Navitoclax Alone or in Combination With Ruxolitinib in Participants With Myelofibrosis

Browse trials for

• Primary Myelofibrosis 418
• Splenomegaly 33

Keywords

• Post-polycythemia vera MF (PPV-MF)
• Post-essential thrombocythemia (PET-MF)
• ruxolitinib
• navitoclax
• splenic volume
• Primary Myelofibrosis
• Jakafi
• enlarged spleen
• splenomegaly
• ABT 263
• bone marrow fibrosis

Primary Myelofibrosis

418 studies on the registry are indexed under Primary Myelofibrosis; 116 are open to participants now.

This study's enrollment of 191 is above the median of 44 across 347 interventional studies indexed under Primary Myelofibrosis.

Lead sponsor

AbbVie is the lead sponsor of 953 studies on the registry; 136 are open to participants now.

Of its 350 completed or terminated interventional studies of FDA-regulated products, 210 (60%) have results posted.

Study arms

• Experimental
  Navitoclax + ruxolitinib (Cohort 1a)

  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).

  Drug: Ruxolitinib · Drug: Navitoclax

• Experimental
  Navitoclax + ruxolitinib (Cohort 1b)

  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).

  Drug: Ruxolitinib · Drug: Navitoclax

• Experimental
  Navitoclax (Cohort 2)

  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).

  Drug: Navitoclax

• Experimental
  Navitoclax + ruxolitinib (Cohort 3)

  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).

  Drug: Ruxolitinib · Drug: Navitoclax

Interventions

• DrugRuxolitinib

  Tablet; Oral

  Also known as: Jakafi

• DrugNavitoclax

  Film-coated tablet; Oral

  Also known as: ABT-263

Primary outcomes

1. Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume at Week 24

   Reduction in spleen volume is measured by magnetic resonance imaging/computerized tomography (MRI/CT).

   Time frame: Baseline, Week 24

Secondary outcomes

1. Percentage of Participants Achieving ≥ 50% Reduction From Baseline in Total System Score (TSS) at Week 24

   TSS is assessed by the Myelofibrosis Symptom Assessment Form (MFSAF) version 4.0. Participants complete a symptom diary and rate the following seven MF symptoms: fatigue, night sweats, abdominal discomfort, pruritus, pain under the ribs on the left side, early satiety, and bone pain daily using a scale from 0 (absent) to 10 (worst imaginable), and the scores are averaged over 7 days, with a minimum of 4 days required to calculate the average score. Participants for whom a valid average score cannot be calculated either at baseline or post-baseline are considered non-responders. The TSS reflects the sum of the scores of these symptoms, for a maximum possible score of 70 (i.e., most severe symptom experience).

   Time frame: Baseline, Week 24

2. Percentage of Participants Achieving Anemia Response

   For a participant who is transfusion independent (TI) at Baseline with hemoglobin value \< 10 g/dL, anemia response is achieved if the post-Baseline hemoglobin level increases by ≥2 g/dL without receiving packed red blood cells (PRBC) transfusion (for any reason) within 2 weeks and without any erythropoietin or mimetics within the last 4 weeks prior to the increase in hemoglobin level by ≥2g/dL was observed. Hemoglobin values more than 30 days after the last dose of study treatment or after the start of post-study treatment or disease progression, whichever is earlier, will not be considered in the analysis of anemia response. For a participant who is transfusion dependent (TD) at Baseline, anemia response is defined as a period of at least 12 consecutive weeks without PRBC transfusion at any time after the first dose of study drug and on or prior to 30 days post last dose of study drug, the start of post-study treatment, disease progression or death, whichever occurs earlier.

   Time frame: Up to 254 weeks

3. Percentage of Participants With ≥ 1 Grade Reduction From Baseline in Fibrosis Grade At Any Time

   Bone marrow grading is assessed according to the European Consensus Grading System. The 4-point grading scale ranges from MF-0, which corresponds to normal bone marrow, to MF-3, diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis.

   Time frame: Up to 254 weeks

4. Time to First Reduction in Fibrosis Grade

   Grade of bone marrow fibrosis was assessed by investigators according to the European Consensus Grading System. The 4-point grading scale ranges from MF-0, which corresponds to normal bone marrow, to MF-3, diffuse and dense increase in reticulin with extensive intersections with coarse bundles of collagen, often associated with significant osteosclerosis. The time to first achieving a reduction of at least 1 grade in bone marrow fibrosis from Baseline was summarized.

   Time frame: Up to 254 weeks

Baseline characteristics

Publications

• Passamonti F, Foran JM, Tandra A, De Stefano V, Fox ML, Mattour A, McMullin MF, Perkins AC, Rodriguez-Macias G, Sibai HA, Polepally AR, Sun Y, Chopra AS, Harb JG, Qin Q, Potluri J, How J. Preliminary Safety and Efficacy of Navitoclax Plus Ruxolitinib in Janus Kinase Inhibitor-Naive Patients With Myelofibrosis From the Multicenter, Open-Label, Phase 2 Study (REFINE). Hematol Oncol. 2026 Mar;44(2):e70180. doi: 10.1002/hon.70180. PubMed 41846295 ↗
• Pemmaraju N, Somervaille TCP, Palandri F, Harrison C, Komrokji RS, Perkins A, Ayala Diaz RM, Lavie D, Tomita A, Feng Y, Qin Q, Harb J, Polepally AR, Potluri J, Garcia JS. Addition of navitoclax to ruxolitinib for patients with myelofibrosis with progression or suboptimal response. Blood Neoplasia. 2024 Nov 2;2(1):100056. doi: 10.1016/j.bneo.2024.100056. eCollection 2025 Feb. PubMed 40454409 ↗
• Pemmaraju N, Garcia JS, Potluri J, Harb JG, Sun Y, Jung P, Qin QQ, Tantravahi SK, Verstovsek S, Harrison C. Addition of navitoclax to ongoing ruxolitinib treatment in patients with myelofibrosis (REFINE): a post-hoc analysis of molecular biomarkers in a phase 2 study. Lancet Haematol. 2022 Jun;9(6):e434-e444. doi: 10.1016/S2352-3026(22)00116-8. Epub 2022 May 13. PubMed 35576960 ↗
• Harrison CN, Garcia JS, Somervaille TCP, Foran JM, Verstovsek S, Jamieson C, Mesa R, Ritchie EK, Tantravahi SK, Vachhani P, O'Connell CL, Komrokji RS, Harb J, Hutti JE, Holes L, Masud AA, Nuthalapati S, Potluri J, Pemmaraju N. Addition of Navitoclax to Ongoing Ruxolitinib Therapy for Patients With Myelofibrosis With Progression or Suboptimal Response: Phase II Safety and Efficacy. J Clin Oncol. 2022 May 20;40(15):1671-1680. doi: 10.1200/JCO.21.02188. Epub 2022 Feb 18. PubMed 35180010 ↗

Study documents

• Study protocol · Oct 4, 2021
• Statistical analysis plan · Jan 31, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: Yes — AbbVie is committed to responsible data sharing regarding the clinical trials we sponsor. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information (e.g., protocols, analyses plans, clinical study reports), as long as the trials are not part of an ongoing or planned regulatory submission. This includes requests for clinical trial data for unlicensed products and indications.

Supporting information: Study protocol, Sap, Csr