A Multi-Center Phase Ib, Open-Label, Dose-Finding Pilot Study to Evaluate the Combination of Carfilzomib and Cyclophosphamide With Dexamethasone Prior to ASCT in Patients With Transplant Eligible Newly Diagnosed Myeloma
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Sponsor
- Criterium, Inc.
- Enrollment
- 29
- Locations
- 5
- Primary Endpoint
- Adverse Events as a measure of safety and tolerability
Study Overview
Brief 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.
Detailed 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.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Carfilzomib, Cyclophosphamide, Dexamethasone
All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.
Intervention: Carfilzomib (Drug)
Carfilzomib, Cyclophosphamide, Dexamethasone
All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.
Intervention: Cyclophosphamide (Drug)
Carfilzomib, Cyclophosphamide, Dexamethasone
All eligible subjects will receive Carfilzomib, Cyclophosphamide, and Dexamethasone.
Intervention: Dexamethasone (Drug)
Outcomes
Primary Outcomes
Adverse Events as a measure of safety and tolerability
Time Frame: Throughout treatment, estimated to be 4-6 months per patients
Review of adverse events for safety and to determine the maximum tolerated dose of the combination treatment.
Secondary Outcomes
- Overall Response after induction therapy(Every 28 days during induction therapy, estimated to be 4-6 months)
- Time to Next Therapy(up to 6 months post ASCT)
- Overall Response post ASCT(3 and 6 months post ASCT)
- Time to Progression(Througout treatment and 3 and 6 months post ASCT)
- Progression Free Survival(up to 6 months post ASCT)