Study of Carfilzomib in Combination With Induction Chemotherapy in Children With Relapsed or Refractory Acute Lymphoblastic Leukemia

Status: Active

Description

The purpose of the study is to determine the maximum tolerated dose and assess the safety, tolerability and activity of carfilzomib, alone and in combination with induction chemotherapy, in children with relapsed or refractory acute lymphoblastic leukemia (ALL).

Eligibility Criteria

Inclusion Criteria

  • Age 21 years or younger at the time of initial ALL diagnosis and age > 1 year at the time of study treatment initiation.
  • Subjects must have a diagnosis of relapsed or refractory ALL with ≥ 5% blasts in the bone marrow (M2 or M3 disease), with or without extramedullary disease. -To be eligible, subjects must have had 1 or more prior therapeutic attempts, defined as:
  • Early first relapse (< 36 months from original diagnosis) after achieving a CR (B-ALL) or first relapse any time following the original diagnosis after achieving a CR (T-ALL)
  • Relapse after achieving a CR following the first or subsequent relapse (i.e., ≥ 2 relapses) OR
  • Failing to achieve a CR from original diagnosis after at least 1 induction attempt
  • Subjects must have fully recovered from the acute toxic effects of all previous chemotherapy, immunotherapy, or radiotherapy treatment before enrollment.
  • Subjects must have a serum creatinine level that is ≤ 1.5 × institutional upper limit of normal (ULN) according to age. If serum creatinine level is > 1.5 × ULN, the subject must have a calculated creatinine clearance or radioisotope glomerular filtration rate (GFR) ≥ 70 mL/min/1.73 m2, or for children<2 years of age, ≥ 50mL/min/1.73 m2.
  • Adequate liver function, defined as both of the following:
  • Total bilirubin ≤ 1.5 × institutional ULN except in the presence of Gilbert Syndrome
  • Alanine aminotransferase (ALT) ≤ 5 × institutional ULN
  • Performance status: Karnofsky or Lansky scores ≥ 50 for subjects > 16 years old or ≤ 16 years old, respectively.

Exclusion Criteria

  • Known allergy to any of the drugs used in the study. (Subjects who have had a previous allergy to PEG-asparaginase but can receive Erwinia are eligible.)
  • Known allergy to Captisol (a cyclodextrin derivative used to solubilize carfilzomib)
  • Left ventricular fractional shortening < 30%
  • History of ≥ Grade 2 pancreatitis
  • Active graft‑versus‑host disease requiring systemic treatment
  • Positive culture for or other clinical evidence of infection with bacteria or fungus within 14 days of the initiation of study treatment
  • Down Syndrome
  • Prior therapy restrictions:
  • Subjects must have completed therapy with granulocyte‑colony stimulating factor (G‑CSF) or other myeloid growth factors at least 7 days before study treatment initiation, or at least 14 days before study treatment initiation, if pegylated myeloid growth factors were administered.
  • Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
  • At least 3 antibody half‑lives must have elapsed since the last dose of monoclonal antibody (e.g., 66 days for rituximab, 69 days for epratuzumab and 30 days for inotuzumab) before subjects may initiate study treatment.
  • Subjects must have completed any type of active immunotherapy (e.g., tumor vaccines) at least 42 days before study treatment initiation.
  • Subjects must not have received other antineoplastic agents with therapeutic intent, excluding hydroxyurea and antimetabolites administered as part of maintenance chemotherapy, within 7 days prior to study treatment initiation

Locations & Contacts

California

Los Angeles
Children's Hospital Los Angeles
Status: Approved
Name Not Available

Georgia

Atlanta
Children's Healthcare of Atlanta - Egleston
Status: Active
Name Not Available

Illinois

Chicago
Lurie Children's Hospital-Chicago
Status: Active
Name Not Available

Maryland

Baltimore
Johns Hopkins University / Sidney Kimmel Cancer Center
Status: Active
Name Not Available

Michigan

Ann Arbor
University of Michigan Comprehensive Cancer Center
Status: Active
Name Not Available

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

Ohio

Columbus
Nationwide Children's Hospital
Status: Active
Name Not Available

Tennessee

Memphis
St. Jude Children's Research Hospital
Status: Temporarily closed to accrual
Name Not Available

Texas

Dallas
UT Southwestern / Simmons Cancer Center-Dallas
Status: Active
Name Not Available
Houston
Texas Children's Hospital
Status: Active
Name Not Available

Utah

Salt Lake City
Primary Children's Hospital
Status: Active
Name Not Available

Trial Phase & Type

Trial Phase

Phase I

Trial Type

Treatment

Lead Organization

Lead Organization
Amgen, Inc.

Trial IDs

Primary ID CFZ008
Secondary IDs NCI-2014-02601, 2014‐001633‐84
Clinicaltrials.gov ID NCT02303821