Relapsed Solid TumorsPhase 1POE14-01NCT02512926
Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children
A Phase 1 study testing Carfilzomib, Cyclophosphamide and Etoposide in people with Relapsed Solid Tumors and Refractory Solid Tumors, run by Stanford University at 8 sites in 2 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 6 months to 29 years
- Conditions the study is for
- Relapsed Solid Tumors, Refractory Solid Tumors, Relapsed Leukemia
- What is being tested?
- Carfilzomib, Cyclophosphamide and Etoposide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 8 sitesin 2 countries
- Study dates
- 16 Feb 2016to 7 Nov 2023
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months to 29 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
- OR
- 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
Show all 30Show fewer
- 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
- Total bilirubin ≤ 1.5 x ULN for age, direct bilirubin ≤ ULN for age
- AST and ALT ≤ 3 x ULN for age unless elevation can be clearly attributed to liver leukemia or metastases
- ECHO shortening fraction ≥ 27%
- Pulse Oximetry measurement ≥ 95% saturation without supplemental oxygen
- Bone marrow function:
- Hgb ≥10 g/dL - can be transfused
- Plts ≥ 75,000 - cannot be transfused (must be ≥ 7 days from last plt transfusion)
- 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
- Reproductive function:
- Female patients of childbearing potential must have a negative serum pregnancy test confirmed within 7 days prior to enrollment
- Female patients with infants must agree not to breastfeed their infants while on the study
- 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
- Written informed consent
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
8 sites in 2 countries.
8 sites in 2 countries
United States7 sites
Dana Farber Cancer Institute
Boston, Massachusetts, 02215
Penn State Hershey Children's Hospital
Hershey, Pennsylvania, 17033-0850
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Memorial Sloan-Kettering Cancer Center
New York, New York, 10065
Stanford University School of Medicine and Stanford Cancer Institute
Palo Alto, California, 94304
Phoenix Children's Hospital
Phoenix, Arizona, 85016
University of Texas Health Science Center at San Antonio
San Antonio, Texas, 78229
About this study
Official title: 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 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.
Read the detailed description
Part 1 of the study will include a dose escalation based on Dose limiting toxicities (DLTs) until the MTD or highest dose level is reached, whichever comes first.
At the MTD or highest dose level (if no MTD is reached), an additional 6 patients will be enrolled to further evaluate safety of the regimen (Part 2).
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
Once an MTD is determined for Strata A or B, if the Study Principal Investigator determines that the study treatment should not be further pursued due to safety or enrollment barriers, the expansion Part or the study will be discontinued.
- Being tested
- Carfilzomib, Cyclophosphamide, Etoposide
- Keywords
- Solid Tumors, Leukemia, Relapsed, Refractory
- Medical subject headings
- Leukemia, Recurrence
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarfilzomibDrug
Carfilzomib in combination with cyclophosphamide and etoposide for children with relapsed and refractory solid tumors and leukemias
CyclophosphamideDrug
EtoposideDrug
| Study group | Role | What they receive |
|---|---|---|
| Carfilzomib | Experimental | Carfilzomib in combination with cyclophosphamide and etoposide Receives: Drug: Carfilzomib; Drug: Cyclophosphamide; Drug: Etoposide |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 30 Days post treatment initiation
Secondary outcomes (8)
To evaluate toxicities of carfilzomib in the pediatric population when combined with conventional chemotherapy.
Record AEs and SAEs
Measured: Treatment initiation through 30 days post treatment
Determine patient response rate (CR, PR, SD, PD) with this regimen
Measured: 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.
Measured: 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
Measured: 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
Measured: Treatment initiation through 30 days post treatment
To measure the level of proteosome inhibition in patient PBMCs before and during treatment by determination of the level of protein ubiquitination
Measured: Treatment initiation through 30 days post treatment
To determine in vitro sensitivity of patient leukemias and solid tumors to carfilzomib alone and in combination with study chemotherapeutic agents in order to generate a predictive model of drug sensitivity
Measured: Treatment initiation through 30 days post treatment
To perform whole exome sequencing (WES) and RNA seq on patient leukemia and solid tumor samples and WES on germ line DNA in order to determine potential mechanisms of drug sensitivity or resistance
Measured: Treatment initiation through 30 days post treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2015 (estimated)
- Study start16 Feb 2016
- Primary completion28 Aug 2021
- Study completion7 Nov 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Relapsed Solid TumorsStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- The Pediatric Oncology Experimental Therapeutics Investigators' Consortium, Amgen
- Responsible party
- Principal investigator, Norman J. Lacayo, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02512926
- Sponsor's protocol ID
- IRB-37313
- Other IDs
- PEDSVAR0042
- Acronym
- POE14-01
- Status last verified
- Oct 2025
- First submitted
- 21 Jul 2015
- Last updated
- 15 Oct 2025
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 40941020