Phase 1 Study of Pevonedistat (MLN4924, IND# 136078), a NEDD8 Activating Enzyme (NAE) Inhibitor, in Combination with Temozolomide and Irinotecan in Pediatric Patients with Recurrent or Refractory Solid Tumors

This phase I trial studies the side effects and best dose of pevonedistat when giving together with irinotecan hydrochloride and temozolomide in treating patients with solid tumors or lymphoma that have come back after a period of improvement or that do not respond to treatment. Pevonedistat and irinotecan hydrochloride may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as temozolomide, work in different ways to stop the growth of cancer cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving pevonedistat, irinotecan hydrochloride, and temozolomide may work better in treating patients with solid tumors or lymphoma.

Principal Investigator:
Kirov, Ivan

Research Coordinator:
Tina Templeman
(714) 509-8646

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  • Clinical Trial Info
  • IRB Number: 1711130
  • Sponsor: COG
  • Protocol Number: ADVL1615
  • NCT Number: NCT03323034
  • Research Type: Adolescents and Young Adults, Recurrent/Refractory Cancer, Solid Tumors
  • Phase: I
  • Status: Active


  • Part A1: ≥ 12 months to < 21 years of age
  • Part A2: ≥ 6 months and < 12 months of age
  • Recurrent or refractory solid tumors, including CNS tumors
  • Must have either measurable or evaluable disease
  • QTc interval < 500 msec
  • Eligible with seizure disorder if on anticonvulsants and well controlled
  • Nervous system disorders resulting from prior therapy must be ≤ Grade 2.
  • INR ≤ 1.5
  • Standard COG Phase 1 organ function requirements


  • Uncontrolled high blood pressure
  • Known cardiopulmonary disease
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment
  • Uncontrolled coagulopathy or bleeding disorder
  • Known cardiopulmonary disease
  • Known hepatic cirrhosis or severe pre-existing hepatic impairment
  • Excluded concomitant medications: Corticosteroids (unless on stable dosing), other investigational drugs, other anti-cancer agents, enzyme-inducing anticonvulsants, anti-GVHD agents post-transplant, androgens, supraphysiologic doses of corticosteroids, erythropeietin, eltrombopag, or romiplostim, strong inducers of CYP3A4 (w/i 14 days)
  • Prior solid organ transplantation