Pevonedistat in Combination With Ruxolitinib for Treatment of Patients With Myelofibrosis

Conditions

• Myelofibroses

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Pevonedistat — DRUG
  The amount of pevonedistat to be administered will be based on body surface area (BSA). BSA will be calculated using a standard formula on Cycle 1 Day 1, and on Day 1 of subsequent cycles if the patient experiences a \> 5% change in body weight from the weight used for the most recent BSA calculation.
• Ruxolitinib — DRUG
  -Standard of care outside of protocol
• Peripheral blood draw — PROCEDURE
  * Baseline or Cycle 1 Day 1 (prior to study treatment administration) * Cycle 2 Day 1 (prior to study treatment administration) * Cycle 4 Day 1 (prior to study treatment administration) * End of treatment
• Skin biopsy — PROCEDURE
  A skin punch biopsy specimen will be collected at the baseline visit. One 6 mm punch biopsy of normal skin will be performed using standard techniques and local anesthesia.

Study Details

Based on the investigators' preclinical data, the combination of pevonedistat and ruxolitinib may provide greater clinical responses in patients with myelofibrosis compared to ruxolitinib monotherapy via inhibition of NFκB in addition to JAK-STAT signaling.

Key Dates

Start date

Apr 23, 2018

Status verified

Dec 2021

Primary completion

Sep 12, 2021

Completion

Oct 4, 2021

Study Design

Enrollment

8 participants (actual)

Allocation

NON_RANDOMIZED

Intervention model

SEQUENTIAL

Primary purpose

TREATMENT

Arms

• Experimental: Arm 1: Starting Dose - 5 mg/m^2 pevonedistat + ruxolitinib
  * Pevonedistat will be given as an IV infusion at the assigned dose over the course of 60 minutes on Days 1, 3, and 5 of each 28-day cycle. * Ruxolitinib will be continued at the same dose as prior to enrollment and will be administered as standard of care outside the study protocol.
• Experimental: Arm 2: Dose Level 2 - 10 mg/m^2 pevonedistat + ruxolitinib
  * Pevonedistat will be given as an IV infusion at the assigned dose over the course of 60 minutes on Days 1, 3, and 5 of each 28-day cycle. * Ruxolitinib will be continued at the same dose as prior to enrollment and will be administered as standard of care outside the study protocol.
• Experimental: Arm 3: Dose Level 3 - 20 mg/m^2 pevonedistat + ruxolitinib
  * Pevonedistat will be given as an IV infusion at the assigned dose over the course of 60 minutes on Days 1, 3, and 5 of each 28-day cycle. * Ruxolitinib will be continued at the same dose as prior to enrollment and will be administered as standard of care outside the study protocol.

Primary Outcome Measure

Safety and tolerability of pevonedistat in combination with ruxolitinib in patients with myelofibrosis as measured by the frequency of adverse events [ Time Frame: Through 30 days after completion of treatment (estimated to be 42 weeks) ]

Locations (1)

Find similar trials in St Louis, MO

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