Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children (POE14-01)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT02512926
Recruitment Status : Recruiting
First Posted : July 31, 2015
Last Update Posted : October 4, 2017
Pediatric Oncology Experimental Therapeutics Investigators' Consortium
Information provided by (Responsible Party):
Jessica Boklan, MD, Phoenix Children's Hospital

July 21, 2015
July 31, 2015
October 4, 2017
July 2015
September 2018   (Final data collection date for primary outcome measure)
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 [ Time Frame: Screening to 2 years ]
Same as current
Complete list of historical versions of study NCT02512926 on Archive Site
  • Collect information on all adverse events that occur with this regimen [ Time Frame: Screening to 2 years ]
  • Determine patient response rate (CR, PR, SD, PD) with this regimen [ Time Frame: Screening to 2 years ]
  • Circulating plasma proteasome (cProt) levels post treatment [ Time Frame: 2 years ]
  • Levels of proteasome activity [ Time Frame: 2 years ]
  • Inhibition of proteasome activity by carfilzomib [ Time Frame: 2 years ]
  • Proteasome inhibition in patient PBMCs before and during treatment by determination of the level of protein ubiquitination. [ Time Frame: 2 years ]
  • In vitro sensitivity of patient leukemias and solid tumors to carfilzomib alone and in combination with study chemotherapeutic agents [ Time Frame: Screening to 2 years ]
  • Alterations of proteasome activity in tumor samples [ Time Frame: 2 years ]
  • Expression of actionable mutations [ Time Frame: 2 years ]
Same as current
Not Provided
Not Provided
Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children
Phase I Study of Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children With Relapsed and Refractory Solid Tumors and Leukemias

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 for the disease being treated in this study. Since carfilzomib has not yet been used in this setting to treat this condition, the investigators must first find the best dose to give. The investigators are looking for the highest dose of carfilzomib that can be given safely. Therefore, not all children taking part in this study will receive the same dose of the study drug in the first part of the trial.

The purpose of this study is to find out what effects, good and/or bad, treatment with a new combination of drugs, cyclophosphamide, etoposide, and carfilzomib has on cancer.

In part 1 of the trial, small groups of children will be enrolled in steps. The first group will be given a certain dose of carfilzomib. If these children do not have side effects which are too bad, the next small group of children enrolled will receive a higher dose. This increase in doses with groups of people will continue until we find the highest dose of the drug that can be given without causing severe or unmanageable side effects.

Part 2 of this study will enroll additional patients at the highest tolerable dose found in Part 1 in order to get more information on side effects and make sure the dose is tolerable.

Phase 1
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • Relapsed Solid Tumors
  • Refractory Solid Tumors
  • Leukemias
  • Drug: Carfilzomib
    Carfilzomib in combination with cyclophosphamide and etoposide for children with relapsed and refractory solid tumors and leukemias
  • Drug: Cyclophosphamide
  • Drug: Etoposide
Experimental: Carfilzomib
Carfilzomib in combination with cyclophosphamide and etoposide
  • Drug: Carfilzomib
  • Drug: Cyclophosphamide
  • Drug: Etoposide
Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Same as current
September 2018
September 2018   (Final data collection date for primary outcome measure)

Inclusion Criteria:

  1. Patients must have either of the following:

    1. 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.


    2. 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.
  2. Age 6 months - 29.99 years at enrollment
  3. Life expectancy ≥ 3 months
  4. Lansky or Karnofsky ≥50
  5. Prior therapy

    1. Patient must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, radiotherapy, or surgery prior to study entry.
    2. 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.
    3. 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
    4. 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.
    5. 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®).
  6. Patient must be ≥ 3 months from hematopoietic stem cell transplant, must not have active GVHD, and must be off all immunosuppression
  7. Organ function:

    1. Either a serum creatinine ≤ ULN for age, or calculated or measured GFR ≥ 70 mL/min/1.73 m2
    2. Total bilirubin ≤ 1.5 x ULN for age, direct bilirubin ≤ ULN for age
    3. AST and ALT ≤ 3 x ULN for age unless elevation can be clearly attributed to liver leukemia or metastases
    4. ECHO shortening fraction ≥ 27%
    5. Pulse Oximetry measurement ≥ 95% saturation without supplemental oxygen
  8. Bone marrow function:

    1. Hgb ≥10 g/dL - can be transfused
    2. Plts ≥ 75,000 - cannot be transfused (must be ≥ 7 days from last plt transfusion)
    3. ANC ≥ 750 - cannot be transfused (must be ≥ 72 hours from last neutrophil infusion)

    However, the plt and ANC requirements can be waived if low counts thought to be secondary to leukemia or tumor bone marrow infiltration

  9. Reproductive function:

    1. Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 7 days prior to enrollment
    2. Female patients with infants must agree not to breastfeed their infants while on the study
    3. Male and female patients of child-bearing potential must agree to use an effective method of contraception approved by the investigator during the study and for a minimum of 3 months after study treatment
  10. Written informed consent

Exclusion Criteria:

  1. Prior treatment with carfilzomib
  2. Known allergy to Captisol® (a cyclodextrin derivative used to solubilize carfilzomib).
  3. Down syndrome
  4. Fanconi Anemia or other underlying bone marrow failure syndrome
  5. Pregnant or lactating females
  6. Known history of Hepatitis B or C or HIV
  7. Patient with any significant concurrent illness
  8. Patient with uncontrolled systemic fungal, bacterial, viral or other infection with ongoing signs/symptoms despite appropriate treatment
  9. 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.
Sexes Eligible for Study: All
6 Months to 29 Years   (Child, Adult)
Contact: Jessica Boklan, MD 602-933-0920
Contact: Aru Narendran, MD, PhD 403-210-6418
Canada,   United States
Not Provided
Not Provided
Jessica Boklan, MD, Phoenix Children's Hospital
Phoenix Children's Hospital
  • Amgen
  • Pediatric Oncology Experimental Therapeutics Investigators' Consortium
Not Provided
Phoenix Children's Hospital
October 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP