A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma

• Status: Completed
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a dose finding pilot study to evaluate the safety and determine the maximum tolerated dose of the combination of carfilzomib and cyclophosphamide with dexamethasone (Car-Cy-Dex) prior to autologous stem cell transplant (ASCT) in patients with newly diagnosed transplant eligible multiple myeloma.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Academic Myeloma Consortium; Criterium, Inc.
• Collaborators: Amgen; Onyx Pharmaceuticals
• Treatments: BB 1101; Cyclophosphamide; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate

Criteria

Inclusion Criteria:

• Cytopathologically or histologically confirmed diagnosis of MM

• Measurable disease, as indicated by one or more of the following:

• Serum M-protein ≥ 1.0 g/dL

• Urine Bence Jones protein ≥ 200 mg/24 hr

• Elevated Free Light Chain as per the International Myeloma Working Group (IMWG) criteria

• Males and females ≥ 18 years of age

• Life expectancy of more than 5 months

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-2

• Adequate hepatic function, with bilirubin < 2 times the upper limit of normal (ULN), and aspartate aminotransferase (AST) and alanine aminotransferase (ALT) < 3.5 times ULN

• Serum Creatinine Clearance(CrCl) ≥ 30 mL/min, either measured or calculated using a standard formula (e.g. Cockcroft and Gault)

• Additional Laboratory Requirements

• Absolute neutrophil count (ANC) ≥1.0 x 109/L

• Hemoglobin ≥8 g/dL [transfusion permitted]

• Platelet count ≥50.0 x 109/L

• Screening ANC should be independent of granulocyte-and granulocyte/macrophage colony stimulating factor (G-CSF and GM-CSF) support for at least 1 week and of pegylated G-CSF for at least 2 weeks

• Patients may receive RBC or platelet transfusions, if clinically indicated, in accordance with institutional guidelines

• Written informed consent in accordance with federal, local, and institutional guidelines

• Patients must agree to practice contraception

• Male patients must agree not to donate semen or sperm.

Exclusion Criteria:

• Patients with non-secretory or hyposecretory MM

• Prior treatment for MM (prior radiation therapy or dexamethasone up to 160 mg for spinal cord compression is allowed. Other limited field radiation involving ≤ 1/3 of the pelvic area is also allowed)

• Plasma cell leukemia

• Pregnant or lactating females

• Major surgery within 21 days prior to first dose

• Congestive heart failure (CHF) (New York Heart Association class III to IV), symptomatic ischemia, conduction abnormalities uncontrolled by conventional intervention or myocardial infarction in the previous six months

• Acute active infection requiring systemic antibiotics, antivirals, or antifungals within 14 days prior to first dose

• Patients receiving active treatment or intervention for any other malignancy or patients who, at the Investigator's discretion, may require active treatment or intervention for any other malignancy within 8 months of starting study treatment.

• Serious psychiatric or medical conditions that could interfere with treatment

• Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose and/or within 14 days before study treatment

• Contraindication to any of the required concomitant drugs, including antiviral (e.g. Valacyclovir) and proton-pump inhibitor (e.g. lansoprazole). Corticosteroid therapy in a dose equivalent to dexamethasone ≥ 1.5 mg/day or prednisone ≥ 10 mg/day. (Steroid use is allowed if necessary to treat spinal cord compression and/or hypocalcaemia.)

• Patients in whom the required program of oral and IV fluid hydration is contraindicated, e.g. due to pre-existing pulmonary, cardiac, or renal impairment

• Patients with primary systemic amyloidosis.