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Study of Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children With Relapsed or Refractory Solid Tumors and Leukemias

This study is currently recruiting participants.
See Contacts and Locations
Verified August 2017 by Memorial Sloan Kettering Cancer Center
Sponsor:
Information provided by (Responsible Party):
Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier:
NCT03273829
First received: September 5, 2017
Last updated: NA
Last verified: August 2017
History: No changes posted
  Purpose
The purpose of this study is to test the safety of carfilzomib in children and young adults given in different doses in combination with cyclophosphamide and etoposide.

Condition Intervention Phase
Leukemia Pediatric Leukemia Pediatric Solid Tumor Drug: Cyclophosphamide Drug: Etoposide Drug: Carfilzomib Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Study of Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children With Relapsed or Refractory Solid Tumors and Leukemias

Resource links provided by NLM:


Further study details as provided by Memorial Sloan Kettering Cancer Center:

Primary Outcome Measures:
  • Dose Limiting Toxicity of study treatment following NCI CTCAE v4.03 [ Time Frame: Up to 2 years ]
    To determine the DLTs of carfilzomib given in combination with cyclophosphamide and etoposide in pediatric patients with relapsed/refractory leukemias and solid tumors, evaluated by NCI CTCAE v4.03

  • Maximum Tolerated Dose of study treatment [ Time Frame: Up to 2 years ]
    To determine the MTD of carfilzomib given in combination with cyclophosphamide and etoposide in pediatric patients with relapsed/refractory leukemias and solid tumors


Estimated Enrollment: 7
Actual Study Start Date: August 31, 2017
Estimated Study Completion Date: August 31, 2019
Estimated Primary Completion Date: August 31, 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Leukemia Drug: Cyclophosphamide
Administered daily on days 1-5: Hour 0-1 Cyclophosphamide IV for 60 minutes ( ± 5 minutes)
Drug: Etoposide
Administered daily on days 1-5: Hour 1-3 Etoposide IV for 120 minutes ( ± 10 minutes)
Drug: Carfilzomib
Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 On Days 1,2 - Carfilzomib IV given from Hour 3-3.5 for 30 minutes (± 5 min) On Days 8,9,15,16 - Carfilzomib IV given alone over 30 min (± 5 min)
Experimental: Solid Tumor (including lymphoma) Drug: Cyclophosphamide
Administered daily on days 1-5: Hour 0-1 Cyclophosphamide IV for 60 minutes ( ± 5 minutes)
Drug: Etoposide
Administered daily on days 1-5: Hour 1-3 Etoposide IV for 120 minutes ( ± 10 minutes)
Drug: Carfilzomib
Carfilzomib will be administered on days 1, 2, 8, 9, 15, 16 On Days 1,2 - Carfilzomib IV given from Hour 3-3.5 for 30 minutes (± 5 min) On Days 8,9,15,16 - Carfilzomib IV given alone over 30 min (± 5 min)

  Eligibility

Ages Eligible for Study:   6 Months to 29 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participants 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
    • Lansky or Karnofsky >/= 50
    • Prior therapy
  • Participant 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 nitrosoureas or mitomycin C. For participants 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. Hydroxyurea is permitted but must be discontinued >/= 24 hours prior to start of protocol therapy.
  • 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).

    • Participants must be >/= 3 months from hematopoietic stem cell transplant, must not have active GVHD, and must be off all immunosuppression

Laboratory

  • Organ function:

    • Either a serum creatinine </= ULN for age, of 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 ply and ANC requirements can be waived if low counts through to be secondary to leukemia or tumor bone marrow infiltration

Ethical/Other

  • Reproductive function

    • Female participants of childbearing potential must have a negative serum pregnancy test confirmed within 7 days prior to enrollment
    • Female participants with infants must agree not to breastfeed their infants while on the study
    • Male and female participants 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

Exclusion Criteria:

  • 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
  • Participant with any significant concurrent illness
  • Participant with uncontrolled systemic fungal, bacterial, viral or other infection with ongoing signs/symptoms despite appropriate treatment
  • Participant with illness, psychiatric disorder or social issue that could compromise participant safety or compliance with the protocol treatment or procedures, interfere with the consent, study participation, follow-up, or interpretation of study results
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT03273829

Contacts
Contact: Tanya Trippett, MD 212-639-8267 trippet1@mskcc.org
Contact: Emily Slotkin, MD 212-639-8856 slotkine@mskcc.org

Locations
United States, Arizona
Ronald Matricaria Institute of Molecular Medicine Not yet recruiting
Phoenix, Arizona, United States, 85004
Contact: Eiman Aleem, PhD    602-827-2078    ealeem@email.arizona.edu   
Phoenix Children'S Hospital Not yet recruiting
Phoenix, Arizona, United States, 85016
Contact: Jessica Boklan, MD    602-546-0920      
United States, Arkansas
Arkansas Children's Hospital Not yet recruiting
Little Rock, Arkansas, United States, 72206
Contact: Kathleen Neville, MD, MS    816-364-4405      
United States, California
Stanford Cancer Center at Stanford University Medical Center and Stanford Cancer Institute Not yet recruiting
Stanford, California, United States, 94305-5750
Contact: Norman J Lacayo, MD    650-497-8953      
United States, Florida
Arnold Palmer Hospital for Children Not yet recruiting
Orlando, Florida, United States, 32806
Contact: Amy Smith, MD    321-841-8588      
United States, Massachusetts
Dana Farber Cancer Institute Not yet recruiting
Boston, Massachusetts, United States, 02115
Contact: Steven DuBois, MD    617-632-5460      
United States, New York
Memorial Sloan - Kettering Cancer Center Recruiting
New York, New York, United States, 10021
Contact: Tanya Trippett, MD    212-639-8267      
United States, Pennsylvania
Pennsylvania State Hershey Children's Hospital Not yet recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Valerie Brown, MD. PhD    717-531-6012      
United States, Texas
Md Anderson Cancer Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Anna Franklin, MD    713-792-2121      
University of Texas Health Science Center at San Antonio Not yet recruiting
San Antonio, Texas, United States, 78229
Contact: Anne-Marie Langevin, MD    210-450-1170      
Canada, Alberta
Alberta Children'S Hospital Not yet recruiting
Calgary, Alberta, Canada, T3B 6A8
Contact: Aru Narendran, MD, PhD    403.210.6418      
Sponsors and Collaborators
Memorial Sloan Kettering Cancer Center
  More Information

Additional Information:
Responsible Party: Memorial Sloan Kettering Cancer Center
ClinicalTrials.gov Identifier: NCT03273829     History of Changes
Other Study ID Numbers: 17-427
Study First Received: September 5, 2017
Last Updated: September 5, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Memorial Sloan Kettering Cancer Center:
17-427
Carfilzomib
Cyclophosphamide
Etoposide
children
pediatric cancer

Additional relevant MeSH terms:
Leukemia
Neoplasms by Histologic Type
Neoplasms
Cyclophosphamide
Etoposide phosphate
Etoposide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors

ClinicalTrials.gov processed this record on September 19, 2017