Study of Oral Navitoclax Tablet In Combination With Oral Ruxolitinib Tablet When Compared With Oral Ruxolitinib Tablet To Assess Change In Spleen Volume In Adult Participants With Myelofibrosis

Browse trials for

• Primary Myelofibrosis 419
• Neoplasms 9,365

Keywords

• Myelofibrosis
• Navitoclax
• Ruxolitinib
• Cancer
• ABT-263
• TRANSFORM-1

Primary Myelofibrosis

419 studies on the registry are indexed under Primary Myelofibrosis; 117 are open to participants now.

This study's enrollment of 252 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

• Active comparator
  Placebo for Navitoclax + Ruxolitinib

  Placebo for 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). Placebo for navitoclax didn't exceed 200 mg QD for first 24 weeks of treatment. After Week 25, Day 1 visit, placebo for navitoclax dose may be increased to 300 mg QD at Investigator's discretion for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Ruxolitinib tablets were administered orally twice daily (BID) per Baseline platelet count (\>200 × 10\^9/L starting dose of 20 mg; 100-200 × 10\^9/L starting dose of 15 mg). Participants will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).

  Drug: Placebo for Navitoclax · Drug: Ruxolitinib

• Experimental
  Navitoclax + Ruxolitinib

  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 25, Day 1 visit, navitoclax dose may be increased to 300 mg QD at Investigator's discretion for those with suboptimal spleen response defined as failure to achieve spleen volume reduction of at least 10% per imaging. Ruxolitinib tablets were administered orally twice daily (BID) per Baseline platelet count (\>200 × 10\^9/L starting dose of 20 mg; 100-200 × 10\^9/L starting dose of 15 mg). Participants will continue their treatment until end of clinical benefit, unacceptable toxicity, or they meet other protocol criteria for discontinuation (whichever occurs first).

  Drug: Ruxolitinib · Drug: Navitoclax

Interventions

• DrugPlacebo for Navitoclax

  Film-coated tablet; Oral

• 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 (SVR35W24)

   Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.

   Time frame: Baseline, Week 24

Secondary outcomes

1. Change From Baseline in Total Symptom Score (TSS) at Week 24 as Measured by Myelofibrosis Symptom Assessment Form (MFSAF) v4.0

   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). Negative changes from Baseline indicate improvement.

   Time frame: Baseline, Week 24

2. Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume (SVR35) at Any Time

   Reduction in spleen volume is measured by magnetic resonance imaging (MRI) or computed tomography (CT), per International Working Group (IWG) criteria.

   Time frame: Up to Week 97

3. Duration of 35% Spleen Volume Reduction (SVR35)

   Duration of SVR35 is defined as the time between the date of first response of spleen volume reduction of 35% achievement to the date of the first assessment where the spleen volume is less than 35% reduction from Baseline and is at least 25% increase from the nadir (the lowest spleen volume), confirmed relapse, or leukemic transformation per International Working Group (IWG) criteria, whichever is earlier.

   Time frame: Baseline (Week 0) Up to Month 48

4. Change From Baseline In Fatigue at Week 24 as Measured by the PROMIS Fatigue Short Form (SF) 7a

   The PROMIS Fatigue SF 7a is a 7-item patient-reported outcome measure that assesses the impact and experience of participants with fatigue over the past 7 days. Each item is scored on a 5-point Likert scale (1 = Never, 2 = Rarely, 3 = Sometimes, 4 = Often, and 5 = Always). Raw scores range from 7 to 35 and are subsequently transformed into a standardized T-score using the PROMIS wave 1 calibration (where a score of 50 represents the U.S. general population mean with a standard deviation of 10). Higher T-scores indicate greater fatigue severity. A decrease in T-score from Baseline represents a clinical improvement in fatigue symptoms.

   Time frame: Baseline, Week 24

5. Change From Baseline at Week 24 in Physical Functioning as Measured by the Physical Functioning Domain of the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ)-C30

   EORTC QLQ-C30 is a 30-item participant self-report questionnaire composed of both multi-item and single scales, including a physical functioning scale. Participants rate items and a score ranging from 0 to 100 is calculated. A higher score on the physical functioning scale indicates a better level of functioning, and positive changes from Baseline indicate improvement.

   Time frame: Baseline, Week 24

6. 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 Week 97

7. Overall Survival (OS)

   OS is defined as the time from the date of randomization to the date of death from any cause.

   Time frame: Up to 50 months

8. Leukemia-Free Survival

   Leukemia-free survival is defined as the number of days from the date of randomization to the onset date of documented leukemia, disease progression due to leukemia, or death due to leukemia, whichever occurs first.

   Time frame: Up to 50 months

9. Percentage of Participants Who Achieved Reduction in Grade of Bone Marrow Fibrosis From Baseline at Any Time

   Change in grade of bone marrow fibrosis was measured per the European consensus grading system through bone marrow biopsy. The percentage of participants who achieved reduction of at least 1 grade in bone marrow fibrosis compared to Baseline is reported.

   Time frame: Up to Week 97

Baseline characteristics

Study documents

• Study protocol · Mar 23, 2023
• Statistical analysis plan · Apr 1, 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 clinical trial data sharing. This includes access to anonymized, individual and trial-level data (analysis data sets), as well as other information.

Supporting information: Study protocol, Sap, Csr