A Safety Study of Carfilzomib, Cyclophosphamide & Dexamethasone Prior to ASCT in Patients With Newly Diagnosed Myeloma (11-MM-01)

Criterium

Status and phase: Completed; Phase 1

Conditions: Multiple Myeloma

Treatments: Drug: Dexamethasone; Drug: Carfilzomib; Drug: Cyclophosphamide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01660750

CAR-IST-520 (Other Identifier)

AMyC 11-MM-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 29 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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29 participants in 1 patient group

Carfilzomib, Cyclophosphamide, Dexamethasone

Experimental group

Description:

All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.

Treatment:

Drug: Cyclophosphamide

Drug: Carfilzomib

Drug: Dexamethasone