Study of Carfilzomib in Multiple Myeloma Relapsed After High-dose Melphalan With Autologous Stem Cell Support

• Status: Unknown status
• Trial end date: 2019-04-01
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates induction therapy with carfilzomib-cyclophosphamide-dexamethasone before salvage high-dose melphalan with autologous stem cell support (HDT) in multiple myeloma patients with relapse after HDT done at diagnosis. In addition, the study evaluates the effect of maintenance therapy after salvage HDT in multiple myeloma. After salvage HDT half of the patients receive maintenance therapy with carfilzomib/dexamethasone while the other half are observed without maintenance therapy.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Henrik Gregersen
• Collaborator: Nordic Myeloma Study Group
• Treatments: BB 1101; Cyclophosphamide; Dexamethasone; Dexamethasone 21-phosphate; Dexamethasone acetate; Melphalan

Criteria

Inclusion Criteria:

• Myeloma diagnosis according to IMWG criteria

• First treatment demanding relapse after HDT according to IMWG criteria

• More than 2.0 x 10m CD34+ stem cells / kg body weight in the freezer for stem cell support

• Signed informed consent given prior to any study related activities have been performed

• Age > 18 years

Exclusion Criteria:

Demographic

• Allogeneic transplantation scheduled as a part of the treatment

• Treatment demanding relapse less than one year after HDT

• Myeloma treatment after the first HDT, except radiotherapy, bisphosphonates, denosumab and corticosteroids less than 6 days for symptom control

• Patients not having received HDT as first line treatment

• Previous treatment with carfilzomib

• Expected survival of less than six months

• Performance status (WHO) ≥ 3

Laboratory

• Serum M-component < 5 g/l and urine M-component < 200 mg/l

• Any of the following laboratory abnormalities:

• Absolute neutrophil count (ANC) < 1.0 × 109/L

• Hemoglobin < 5 mmol/L (<80 g/L) (prior RBC transfusion or recombinant human erythropoietin use is permitted)

• Platelet count < 50 × 109/L (< 30 × 109/L if myeloma involvement in the bone marrow is > 50%)

• Serum ALT or AST > 3.5 times the upper limit of normal and serum direct bilirubin > 34 µmol/L (2 mg/dL)

• Creatinine clearance (CrCl) < 15 mL/minute, either measured or calculated using a standard formula

Concurrent conditions

• Concurrent disease making treatment with carfilzomib, cyclophosphamide or dexamethasone unsuitable

• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to enrolment

• Major surgery within 21 days prior to enrolment

• Acute active infection requiring treatment

• Known or suspected hypersensitivity or intolerance to melphalan, dexamethasone or Captisol® (a cyclodextrin derivative)

• Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, NYHA Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, uncontrolled severe arrhythmias, or cardiac amyloidosis

• LVEF <40%, determined by 2-D transthoracic echocardiogram (ECHO) or Multigated Acquisition Scan (MUGA)

• Pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to enrolment

• Serious hepatic disorder, including active hepatitis B or C infection

• Other serious medical or psychiatric illness likely to interfere with participation in this clinical study

• Use of any investigational agents or experimental medical device within 28 days prior to enrolment into the study

Ethical/other

• Pregnant or lactating females

• Females of childbearing potential must agree to ongoing pregnancy testing and to practice contraception

• Male subjects must agree to practice contraception