Carfilzomib/Cyclophosphamide/Dexamethasone with Maintenance Carfilzomib in Multiple Myeloma

NCT02315716 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: UCL/12/05002014-000506-35
• Study Type: interventional
• Target: 281
• Locations: 1 country
• Sites: 20

Brief Summary

The Cardamon trial is a phase 2 trial using the standard chemotherapy drugs cyclophosphamide and dexamethasone in combination with a new drug called Carfilzomib in patients with multiple myeloma.

Conditions

Multiple Myeloma

Keywords

Multiple Myeloma; Carfilzomib

Outcome Measures

Primary Outcomes (2)

• Response rate

  Major response rate (sCR, CR \& VGPR) to 4 cycles of CarCyDex

  Within 4 weeks of the end of induction treatment

• PFS

  Progression free survival at 2 years for both ASCT and non-ASCT (consolidation) arms

  2 years after randomisation

Secondary Outcomes (6)

• To assess toxicity and tolerability of CarCyDex and carfilzomib as maintenance therapy in untreated patients with symptomatic multiple myeloma

  From start of treatment until 30 days post end of maintenance treatment

• Disease response rate

  Within 4 weeks of the end of induction treatment

• PFS

  Assessed every 6 months from the end of treatment until 36 months post induction

• Overall survival

  Assessed every 6 months from the end of treatment until 36 months post induction

• MRD conversion following treatment

  Baseline, Day 100 post ASCT or within 4 weeks of the end of consolidation treatment

Study Arms (2)

Consolidation with 4 cycles of CarCyDex

EXPERIMENTAL

Patients responding to induction treatment will receive 4 further cycles of Carfilzomib, Cyclophosphamide and Dexamethasone (CarCyDex) treatment followed by 18 months of maintenance carfilzomib

Drug: Consolidation with 4 cycles of CarCyDex

Autologous Stem Cell Transplant (ASCT)

ACTIVE COMPARATOR

Patients responding to induction treatment will receive a melphalan conditioned autologous stem cell transplant followed by 18 months of maintenance carfilzomib

Procedure: Autologous Stem Cell Transplant (ASCT)

Interventions

Autologous Stem Cell Transplant (ASCT) PROCEDURE

Randomisation to melphalan conditioned autologous stem cell transplant

Autologous Stem Cell Transplant (ASCT)

Consolidation with 4 cycles of CarCyDex DRUG

Randomisation to 4 further cycles of Carfilzomib, Cyclophosphamide and Dexamethasone for responding patients following 4 cycles of induction chemotherapy

Consolidation with 4 cycles of CarCyDex

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Previously untreated patients with symptomatic MM (see appendix 3) eligible for stem cell transplantation, with the exception of the following treatments:
• local radiotherapy to relieve bone pain and/or spinal cord compression
• bisphosphonates
• corticosteroids within the last 3 months. Within 14 days prior to study entry, the maximum permitted dose is 160mg (i.e. 4 days of Dexamethasone at 40mg, or equivalent), unless otherwise agreed by the TMG.
• Suitable for high dose therapy and ASCT
• Age ≥ 18 years
• Life expectancy ≥ 3 months
• Eastern Cooperative Oncology Group (ECOG) performance status 0-2)
• Measurable disease as defined by one of the following:
• Secretory myeloma: Monoclonal protein in the serum (≥10 g/L) or monoclonal light chain in the urine (Bence Jones protein ≥200mg/24hours), or serum free light chain (SFLC, involved light chain ≥100mg/L provided the FLC ratio is abnormal)
• Non-secretory myeloma:
• Either ≥30% clonal plasma cells in bone marrow (aspirate or trephine)
• Or 10-30% clonal plasma cells in the marrow and \>1 soft tissue or extra-osseous plasmacytoma ≥ 2 cm that is measurable for response assessment by CT or MRI
• Adequate hepatic function, with serum ALT ≤ 3.5 times the upper limit of normal and serum direct bilirubin ≤ 2 mg/dL (34 µmol/L) within 14 days prior to registration
• Absolute neutrophil count (ANC) ≥ 1.0 × 109/L within 14 days prior to registration and subject has not received any growth factor support within 7 days of testing. ANC≥0.8x109/L allowed for patients with racial neutropenia.

You may not qualify if:

• Pregnant or breast-feeding females (lactating women may participate if breastfeeding ceases for the duration of trial treatment and until 12 months after last treatment)
• Previous systemic chemotherapy for myeloma, with the exception of steroids, as detailed above (see section 6.3.1)
• Any major surgery within 21 days prior to registration which in the investigator's opinion would compromise trial treatment and/or the patient's ability to comply with trial visits. Surgery to relieve spinal cord compression or for treatment of bone fractures is permitted.
• Acute active infection requiring treatment (systemic antibiotics, antivirals, or antifungals) 7 days prior to planned start of treatment, unless otherwise agreed by the TMG.
• Known human immunodeficiency virus (HIV) infection
• Active hepatitis B or C infection (refer to appendix 4)
• Unstable angina or myocardial infarction within 4 months prior to registration, NYHA Class III or IV heart failure, uncontrolled angina, history of severe coronary artery disease, severe uncontrolled ventricular arrhythmias, sick sinus syndrome, or electrocardiographic evidence of acute ischemia or Grade 3 conduction system abnormalities unless subject has a pacemaker
• Uncontrolled hypertension or uncontrolled diabetes within 14 days prior to registration
• Non-haematologic malignancy within the past 3 years with the exception of a) adequately treated basal cell carcinoma, squamous cell skin cancer, or thyroid cancer; b) carcinoma in situ of the cervix or breast; c) prostate cancer of Gleason Grade 6 or less with stable prostate-specific antigen levels; or d) cancer considered cured by surgical resection or unlikely to impact survival during the duration of the study, such as localised transitional cell carcinoma of the bladder or benign tumors of the adrenal or pancreas
• Significant neuropathy (Grades 3-4, or Grade 2 with pain) within 14 days prior to registration
• Known history of allergy to Captisol® (a cyclodextrin derivative used to solubilise carfilzomib)
• Contraindication to any of the required concomitant drugs or supportive treatments, including hypersensitivity to all anticoagulation and antiplatelet options, antiviral drugs, or intolerance to hydration due to preexisting pulmonary, cardiac or renal impairment
• Patients with pleural effusions requiring thoracentesis or ascites requiring paracentesis within 14 days prior to registration
• Any other clinically significant medical disease or condition that, in the Investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Sponsors & Collaborators

• University College, London: lead
• Amgen: collaborator

Study Sites (20)

Queen's Hospital

Romford, Essex, RM7 0AG, United Kingdom

Location

Royal United Hospital

Bath, BA1 3NG, United Kingdom

Location

Birmingham Heartlands Hospital

Birmingham, B9 5SS, United Kingdom

Location

NHS Lanarkshire

Bothwell, United Kingdom

Location

Bradford Royal Infirmary

Bradford, United Kingdom

Location

Kent and Canterbury Hospital

Canterbury, CT1 3NH, United Kingdom

Location

University Hospital of Wales

Cardiff, CF14 4XW, United Kingdom

Location

Medway NHS Foundation Trust

Gillingham, ME7 5NY, United Kingdom

Location

St James' Hospital

Leeds, LS9 7TF, United Kingdom

Location

St Bartholomew's Hospital

London, EC1A 7BE, United Kingdom

Location

Barnet Hospital

London, EN5 3DJ, United Kingdom

Location

Guy's Hospital

London, SE1 9RT, United Kingdom

Location

King's College Hospital

London, SE5 9RS, United Kingdom

Location

St George's Hospital

London, SW17 0QT, United Kingdom

Location

University College London Hospital

London, United Kingdom

Location

Maidstone and Tunbridge Wells

Maidstone, United Kingdom

Location

Churchill Hospital

Oxford, OX3 7LE, United Kingdom

Location

Royal Hallamshire Hospital

Sheffield, S10 2SB, United Kingdom

Location

Royal Stoke University Hospital

Stoke, United Kingdom

Location

City Hospital Sunderland

Sunderland, United Kingdom

Location

Related Publications (1)

• Yong K, Wilson W, de Tute RM, Camilleri M, Ramasamy K, Streetly M, Sive J, Bygrave CA, Benjamin R, Chapman M, Chavda SJ, Phillips EH, Del Mar Cuadrado M, Pang G, Jenner R, Dadaga T, Kamora S, Cavenagh J, Clifton-Hadley L, Owen RG, Popat R. Upfront autologous haematopoietic stem-cell transplantation versus carfilzomib-cyclophosphamide-dexamethasone consolidation with carfilzomib maintenance in patients with newly diagnosed multiple myeloma in England and Wales (CARDAMON): a randomised, phase 2, non-inferiority trial. Lancet Haematol. 2023 Feb;10(2):e93-e106. doi: 10.1016/S2352-3026(22)00350-7. Epub 2022 Dec 15.

  PMID: 36529145 DERIVED

MeSH Terms

Conditions

Multiple Myeloma

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Study Officials

• Kwee Yong

  University College, London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 3, 2014
• First Posted: December 12, 2014
• Study Start: June 16, 2015
• Primary Completion: November 1, 2019
• Study Completion (Estimated): November 1, 2029
• Last Updated: December 6, 2024

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (20)