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

Leukemia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03273829
• Other study ID #: 17-427
• Status: Recruiting
• Phase: Phase 1
• First received: September 5, 2017
• Last updated: September 5, 2017
• Start date: August 31, 2017
• Est. completion date: August 31, 2019

Study information

• Verified date: August 2017
• Source: Memorial Sloan Kettering Cancer Center
• Contact: Tanya Trippett, MD
• Phone: 212-639-8267
• Email: trippet1[@]mskcc.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 7
• Est. completion date: August 31, 2019
• Est. primary completion date: August 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 29 Years

Eligibility

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

Related Conditions & MeSH terms

• Leukemia
• Pediatric Leukemia
• Pediatric Solid Tumor

Intervention

Drug:
• Cyclophosphamide
Administered daily on days 1-5: Hour 0-1 Cyclophosphamide IV for 60 minutes ( ± 5 minutes)
• Etoposide
Administered daily on days 1-5: Hour 1-3 Etoposide IV for 120 minutes ( ± 10 minutes)
• 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)

Locations

Country	Name	City	State
Canada	Alberta Children'S Hospital	Calgary	Alberta
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Pennsylvania State Hershey Children's Hospital	Hershey	Pennsylvania
United States	Md Anderson Cancer Center	Houston	Texas
United States	Arkansas Children's Hospital	Little Rock	Arkansas
United States	Memorial Sloan - Kettering Cancer Center	New York	New York
United States	Arnold Palmer Hospital for Children	Orlando	Florida
United States	Phoenix Children'S Hospital	Phoenix	Arizona
United States	Ronald Matricaria Institute of Molecular Medicine	Phoenix	Arizona
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	Stanford Cancer Center at Stanford University Medical Center and Stanford Cancer Institute	Stanford	California

Sponsors (1)

Lead Sponsor	Collaborator
Memorial Sloan Kettering Cancer Center

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Dose Limiting Toxicity of study treatment following NCI CTCAE v4.03	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	Up to 2 years
Primary	Maximum Tolerated Dose of study treatment	To determine the MTD of carfilzomib given in combination with cyclophosphamide and etoposide in pediatric patients with relapsed/refractory leukemias and solid tumors	Up to 2 years

External Links

•   Memorial Sloan Kettering Cancer Center