NCT02512926

Brief Summary

This study evaluates the use of carfilzomib in combination with cyclophosphamide and etoposide for children with relapsed/refractory solid tumors or leukemia. The medications cyclophosphamide and etoposide are standard drugs often used together for the treatment of cancer in children with solid tumors or leukemia. Carfilzomib is FDA (Food and Drug Administration) approved in the United States for adults with multiple myeloma (a type of cancer). However, this drug is not approved to treat children with relapsed/refractory solid tumors or leukemia. With this research, we plan to determine the DLTs and MTD of Carfilzomib given in combination with cyclophosphamide and etoposide in pediatric patients with relapsed/refractory leukemias and solid tumors.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
4

participants targeted

Target at below P25 for phase_1

Timeline
Completed

Started Feb 2016

Longer than P75 for phase_1

Geographic Reach
2 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 21, 2015

Completed
10 days until next milestone

First Posted

Study publicly available on registry

July 31, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

February 16, 2016

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 28, 2021

Completed
2.2 years until next milestone

Study Completion

Last participant's last visit for all outcomes

November 7, 2023

Completed
Last Updated

October 15, 2025

Status Verified

October 1, 2025

Enrollment Period

5.5 years

First QC Date

July 21, 2015

Last Update Submit

October 10, 2025

Conditions

Relapsed Solid TumorsRefractory Solid TumorsRelapsed LeukemiaRefractory Leukemia

Keywords

Solid TumorsLeukemiaRelapsedRefractory

Outcome Measures

Primary Outcomes (1)

  • To determine the DLTs and MTD of carfilzomib given in combination with cyclophosphamide and etoposide in pediatric patients with relapsed/refractory leukemias and solid tumors

    30 Days post treatment initiation

Secondary Outcomes (8)

  • To evaluate toxicities of carfilzomib in the pediatric population when combined with conventional chemotherapy.

    Treatment initiation through 30 days post treatment

  • Determine patient response rate (CR, PR, SD, PD) with this regimen

    Treatment initiation through 30 days post treatment

  • To measure if circulating plasma proteosome (cProt) levels post treatment correlate with response to therapy and overall survival.

    Treatment initiation through 30 days post treatment

  • To measure if the levels of proteasome activity and resistance to carfilzomib correlates with toxicity and/or response to treatment

    Treatment initiation through 30 days post treatment

  • To measure if inhibition of proteasome activity by carfilzomib results in alteration in a number of autophagy and apoptosis related proteins, providing means to evaluate correlates of activity of carfilzomib

    Treatment initiation through 30 days post treatment

  • +3 more secondary outcomes

Study Arms (1)

Carfilzomib

EXPERIMENTAL

Carfilzomib in combination with cyclophosphamide and etoposide

Drug: CarfilzomibDrug: CyclophosphamideDrug: Etoposide

Interventions

CarfilzomibDRUG

Carfilzomib in combination with cyclophosphamide and etoposide for children with relapsed and refractory solid tumors and leukemias

Carfilzomib
CyclophosphamideDRUG
Carfilzomib
EtoposideDRUG
Carfilzomib

Eligibility Criteria

Age6 Months - 29 Years
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64)

You may qualify if:

  • Patients must have either of the following:
  • Relapsed/refractory leukemia in 2nd or greater relapse or who have failed at least one re-induction attempt after relapse or for refractory disease. Patients must meet the WHO classification with ≥ 5% blasts in the bone marrow or must have definitive extramedullary disease (e.g. chloromas, skin lesions). Patients may have asymptomatic CNS 1 or CNS 2 disease, but not CNS 3 or symptomatic CNS disease.
  • Relapsed/refractory non-CNS solid tumor that has not responded or has relapsed and for which no standard treatment is available. Patients may not have primary CNS tumors or CNS metastases. Lymphoma patients are permitted. Patients do not need to have measurable disease.
  • Age 6 months - 29.99 years at enrollment
  • Life expectancy ≥ 3 months
  • Lansky or Karnofsky ≥50
  • Prior therapy
  • Patient must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, radiotherapy, or surgery prior to study entry.
  • Myelosuppressive therapy- At least 14 days must have elapsed since the administration of previous therapy. Six weeks must have elapsed from the administration of nitrosureas or mitomycin C. For patients with ALL on maintenance therapy, they may be eligible if 7 days have elapsed and they are recovered from the toxic effects of the chemotherapy. This restriction does not include intrathecal chemotherapy, which is permitted.
  • Biologic agents- At least 14 days must have elapsed since the completion of therapy with a biologic agent such as a monoclonal antibody. Seven days must have elapsed since the last dose of retinoids
  • Radiation therapy - At least 14 days must have elapsed for local XRT. At least 90 days must have elapsed if prior radiation to ≥50% of the pelvis, the spine, or other substantial bone marrow radiation including TBI.
  • Hematopoietic growth factors- At least 7 days must have elapsed since the last dose of G-CSF or GM-CSF. At least 14 days must have elapsed since last dose of pegfilgrastim (Neulasta®).
  • Patient must be ≥ 3 months from hematopoietic stem cell transplant, must not have active GVHD, and must be off all immunosuppression
  • Organ function:
  • Either a serum creatinine ≤ ULN for age, or calculated or measured GFR ≥ 70 mL/min/1.73 m2
  • +14 more criteria

You may not qualify if:

  • Prior treatment with carfilzomib
  • Known allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
  • Down syndrome
  • Fanconi Anemia or other underlying bone marrow failure syndrome
  • Pregnant or lactating females
  • Known history of Hepatitis B or C or HIV
  • Patient with any significant concurrent illness
  • Patient with uncontrolled systemic fungal, bacterial, viral or other infection with ongoing signs/symptoms despite appropriate treatment
  • Patient with illness, psychiatric disorder or social issue that could compromise patient safety or compliance with the protocol treatment or procedures, or interfere with the consent, study participation, follow-up, or interpretation of study results.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

Phoenix Children's Hospital

Phoenix, Arizona, 85016, United States

Location

Arkansas Children's Hospital

Little Rock, Arkansas, 72202, United States

Location

Stanford University School of Medicine and Stanford Cancer Institute

Palo Alto, California, 94304, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan-Kettering Cancer Center

New York, New York, 10065, United States

Location

Penn State Hershey Children's Hospital

Hershey, Pennsylvania, 17033-0850, United States

Location

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

Location

Alberta Children's Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Related Publications (1)

  • Boklan J, Langevin AM, Bielamowicz K, Neville K, Trippett T, Brown V, DuBois SG, Eshun F, Gelfond J, Zomet A, Narendran A, Lacayo NJ. A Phase I Study of Carfilzomib with Cyclophosphamide and Etoposide in Relapsed and Refractory Leukemia and Solid Tumors. Cancers (Basel). 2025 Sep 6;17(17):2924. doi: 10.3390/cancers17172924.

    PMID: 40941020BACKGROUND

Related Links

MeSH Terms

Conditions

LeukemiaRecurrence

Interventions

carfilzomibCyclophosphamideEtoposide

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsHematologic DiseasesHemic and Lymphatic DiseasesDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Phosphoramide MustardsNitrogen Mustard CompoundsMustard CompoundsHydrocarbons, HalogenatedHydrocarbonsOrganic ChemicalsPhosphoramidesOrganophosphorus CompoundsPodophyllotoxinTetrahydronaphthalenesNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicPolycyclic CompoundsGlucosidesGlycosidesCarbohydrates

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Principal Investigator

Study Record Dates

First Submitted

July 21, 2015

First Posted

July 31, 2015

Study Start

February 16, 2016

Primary Completion

August 28, 2021

Study Completion

November 7, 2023

Last Updated

October 15, 2025

Record last verified: 2025-10

Locations

CA(1)US(7)