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

Conditions

• Myelofibrosis (MF)

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ruxolitinib — DRUG
  Tablet; Oral
• Navitoclax — DRUG
  Film-coated tablet; Oral

Study Details

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.

Key Dates

Start date

Oct 31, 2017

Status verified

Dec 2025

Primary completion

Mar 28, 2022

Completion

Jan 29, 2025

Study Design

Enrollment

191 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

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).
• 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).
• 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).
• 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).

Primary Outcome Measure

Percentage of Participants With ≥ 35% Reduction From Baseline in Spleen Volume at Week 24 [ Time Frame: Baseline, Week 24 ]

Locations (33)

Find similar trials in Birmingham, AL

Related Studies

• MethoTRExATE in MyelOpRolifErative Neoplasms (TREATMORE) Trial
  PHASE2 · Recruiting · Icahn School of Medicine at Mount Sinai · New York, New York
• Phase I/II Clinical Trial of Axatilimab, a CSF1R Monoclonal Antibody, in Combination With Ruxolitinib as Therapy for Patients With Myelofibrosis (MF) and Chronic Myelomonocytic Leukemia (CMML)
  PHASE1/PHASE2 · Recruiting · M.D. Anderson Cancer Center · Houston, Texas
• TACrolimus Targeted Immunosuppression Cessation in ALlogeneic HCT
  PHASE1 · Not Yet Recruiting · Stanford University · Palo Alto, California
• MPN PROGRESSion Registry: Observational Study Tracking Symptoms, Treatments, and Disease Progression in People With Myeloproliferative Neoplasms (MPNs)
  Recruiting · MPN Research Foundation · Chicago, Illinois