Clinical Trials /

Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children

NCT02512926

Description:

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.

Related Conditions:
  • Leukemia
  • Lymphoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children
  • Official Title: Phase I Study of Carfilzomib in Combination With Cyclophosphamide and Etoposide for Children With Relapsed and Refractory Solid Tumors and Leukemias

Clinical Trial IDs

  • ORG STUDY ID: POE14-01
  • NCT ID: NCT02512926

Conditions

  • Relapsed Solid Tumors
  • Refractory Solid Tumors
  • Leukemias

Interventions

DrugSynonymsArms
CarfilzomibCarfilzomib
CyclophosphamideCarfilzomib
EtoposideCarfilzomib

Purpose

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.

Detailed Description

      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.
    

Trial Arms

NameTypeDescriptionInterventions
CarfilzomibExperimentalCarfilzomib in combination with cyclophosphamide and etoposide
  • Carfilzomib
  • Cyclophosphamide
  • Etoposide

Eligibility Criteria

        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.

                  OR

               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.
      
Maximum Eligible Age:29 Years
Minimum Eligible Age:6 Months
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Collect information on all adverse events that occur with this regimen
Time Frame:Screening to 2 years
Safety Issue:
Description:
Measure:Determine patient response rate (CR, PR, SD, PD) with this regimen
Time Frame:Screening to 2 years
Safety Issue:
Description:
Measure:Circulating plasma proteasome (cProt) levels post treatment
Time Frame:2 years
Safety Issue:
Description:
Measure:Levels of proteasome activity
Time Frame:2 years
Safety Issue:
Description:
Measure:Inhibition of proteasome activity by carfilzomib
Time Frame:2 years
Safety Issue:
Description:
Measure:Proteasome inhibition in patient PBMCs before and during treatment by determination of the level of protein ubiquitination.
Time Frame:2 years
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Alterations of proteasome activity in tumor samples
Time Frame:2 years
Safety Issue:
Description:
Measure:Expression of actionable mutations
Time Frame:2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Phoenix Children's Hospital

Trial Keywords

  • Solid Tumors
  • Leukemia
  • Relapsed
  • Refractory

Last Updated

April 7, 2016