a safety study of carfilzomib, cyclophosphamide & dexamethasone prior to asct in patients with newly diagnosed myeloma

Conditions: Multiple Myeloma

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.

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. the study will also explore the efficacy of car-cy-dex including overall response after induction therapy, overall response at 3 and 6 months post asct, and time to progression, progression free survival, and time to next therapy if it occurs within 6 months post asct.

Eligibility 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.

Keywords: newly diagnosed multiple myeloma transplant eligible multiple myeloma