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Carfilzomib/Cyclophosphamide/Dexamethasone With Maintenance Carfilzomib in Multiple Myeloma (Cardamon)

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ClinicalTrials.gov Identifier: NCT02315716
Recruitment Status : Active, not recruiting
First Posted : December 12, 2014
Last Update Posted : July 22, 2019
Sponsor:
Collaborator:
Amgen (Europe) GmbH
Information provided by (Responsible Party):
University College, London

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.

Condition or disease Intervention/treatment Phase
Multiple Myeloma Procedure: Autologous Stem Cell Transplant (ASCT) Drug: Consolidation with 4 cycles of CarCyDex Phase 2

Detailed Description:

Multiple Myeloma is a cancer of the bone marrow and, for those patients that are young and fit enough, the disease is usually treated with chemotherapy (sometimes called induction chemotherapy) followed by a stem cell transplant using the patient's own stem cells (autograft or Autologous Stem Cell Transplant). Unfortunately almost all patients will experience a relapse at some point following this treatment. After relapse there are a number of treatment options but eventually the disease will become resistant to further therapy.

The use of an Autologous Stem Cell Transplant (or Transplant) after initial chemotherapy treatment has been shown in studies to increase the amount of time that patients are without symptoms of their myeloma before unfortunately their disease relapses. However, recently more effective induction chemotherapy regimens have been developed and patients treated with these new regimens are able to achieve higher and deeper responses than those previously treated on older regimens. Many also achieve complete or very good partial response, which was rare with the traditional chemotherapy regimens.

So, the investigators now do not know if giving patients an Autologous Stem Cell Transplant straight after their initial induction chemotherapy is the best thing to do. It may be that patients who respond well to a new drug containing regimen will obtain most benefit from their stem cells if these stem cells are frozen and stored, so that they can be used when their disease relapses.

In the Cardamon trial, the investigators will directly compare the outcome of patients who receive a transplant, versus those patients who do not and who instead receive Consolidation therapy. After induction treatment and stem cell harvest, patients will be randomly allocated to receive either a transplant or to receive consolidation therapy. Patients in the Cardamon trial will also be given maintenance treatment. This is treatment that is given on an ongoing basis, after the transplant or after the Consolidation therapy. The aim of maintenance treatment is to prolong disease response and delay the time to relapse.

In summary the purpose of the Cardamon study is:

  1. to confirm the high response rate to a new treatment regime that includes Carfilzomib plus 2 standard chemotherapy drugs used for the treatment of Multiple Myeloma,
  2. to investigate whether patients who respond well to this new Carfilzomib-containing induction regimen are able to maintain a long remission period without having an Autologous Stem Cell Transplant 'up-front', and
  3. to find out if maintenance treatment with Carfilzomib is able to further reduce the number of remaining myeloma cells in the bone marrow, using the Minimal Residual Disease test.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 281 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Carfilzomib/Cyclophosphamide/Dexamethasone With Maintenance Carfilzomib in Untreated Transplant-eligible Patients With Symptomatic MM to Evaluate the Benefit of Upfront ASCT
Actual Study Start Date : June 16, 2015
Estimated Primary Completion Date : November 2019
Estimated Study Completion Date : November 2029


Arm Intervention/treatment
Experimental: Consolidation with 4 cycles of CarCyDex
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
Randomisation to 4 further cycles of Carfilzomib, Cyclophosphamide and Dexamethasone for responding patients following 4 cycles of induction chemotherapy

Active Comparator: ASCT
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)
Randomisation to melphalan conditioned autologous stem cell transplant




Primary Outcome Measures :
  1. Response rate [ Time Frame: Within 4 weeks of the end of induction treatment ]
    Major response rate (sCR, CR & VGPR) to 4 cycles of CarCyDex

  2. PFS [ Time Frame: 2 years after randomisation ]
    Progression free survival at 2 years for both ASCT and non-ASCT (consolidation) arms


Secondary Outcome Measures :
  1. Toxicity [ Time Frame: From start of treatment until 30 days post end of maintenance treatment ]
    Adverse Events (including peripheral neuropathy), dose reductions and delays, tolerability of the induction and maintenance regimens (treatment delays, discontinuation rates)

  2. Disease response rate [ Time Frame: Within 4 weeks of the end of induction treatment ]
    Disease response rate (sCR, CR, VGPR, PR) to CarCyDex induction

  3. PFS [ Time Frame: Assessed every 6 months from the end of treatment until 36 months post induction ]
    PFS in both the ASCT and non-ASCT arms

  4. Overall survival [ Time Frame: Assessed every 6 months from the end of treatment until 36 months post induction ]
    Overall survival in both the ASCT and non-ASCT arms

  5. MRD conversion following treatment [ Time Frame: Baseline, Day 100 post ASCT or within 4 weeks of the end of consolidation treatment ]
    Improvement in disease response and conversion from MRD-positive to MRD-negative post ASCT and post Consolidation

  6. MRD conversion following maintenance [ Time Frame: Baseline, after 6 months of maintenance ]
    Improvement in disease response and conversion from MRD-positive to MRD-negative after 6 months of maintenance treatment



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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.
  • Haemoglobin ≥ 8 g/dL (80 g/L) within 14 days prior to registration (subjects may be receiving red blood cell (RBC) transfusions in accordance with institutional guidelines)
  • Platelet count ≥ 75 × 109/L (≥ 50 × 109/L if myeloma involvement in the bone marrow is > 50%) within 14 days prior to registration and subject has not received any platelet transfusions within 7 days prior to testing.
  • Creatinine clearance (CrCl) ≥ 30 mL/minute within 14 days prior to registration, either measured or calculated using a standard formula (e.g. Cockcroft and Gault).
  • Written informed consent
  • Females of childbearing potential (FCBP) must agree to ongoing pregnancy testing and to practice contraception.
  • Male subjects must agree to practice contraception.

Exclusion criteria

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02315716


Locations
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United Kingdom
Queen's Hospital
Romford, Essex, United Kingdom, RM7 0AG
Royal United Hospital
Bath, United Kingdom, BA1 3NG
Birmingham Heartlands Hospital
Birmingham, United Kingdom, B9 5SS
NHS Lanarkshire
Bothwell, United Kingdom
Bradford Royal Infirmary
Bradford, United Kingdom
Kent and Canterbury Hospital
Canterbury, United Kingdom, CT1 3NH
University Hospital of Wales
Cardiff, United Kingdom, CF14 4XW
Medway NHS Foundation Trust
Gillingham, United Kingdom, ME7 5NY
St James' Hospital
Leeds, United Kingdom, LS9 7TF
St Bartholomew's Hospital
London, United Kingdom, EC1A 7BE
Barnet Hospital
London, United Kingdom, EN5 3DJ
Guy's Hospital
London, United Kingdom, SE1 9RT
King's College Hospital
London, United Kingdom, SE5 9RS
St George's Hospital
London, United Kingdom, SW17 0QT
University College London Hospital
London, United Kingdom
Maidstone and Tunbridge Wells
Maidstone, United Kingdom
Churchill Hospital
Oxford, United Kingdom, OX3 7LE
Royal Hallamshire Hospital
Sheffield, United Kingdom, S10 2SB
Royal Stoke University Hospital
Stoke, United Kingdom
City Hospital Sunderland
Sunderland, United Kingdom
Sponsors and Collaborators
University College, London
Amgen (Europe) GmbH
Investigators
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Principal Investigator: Kwee Yong University College, London

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Responsible Party: University College, London
ClinicalTrials.gov Identifier: NCT02315716     History of Changes
Other Study ID Numbers: UCL/12/0500
First Posted: December 12, 2014    Key Record Dates
Last Update Posted: July 22, 2019
Last Verified: July 2019

Keywords provided by University College, London:
Multiple Myeloma
Carfilzomib

Additional relevant MeSH terms:
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Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone
Dexamethasone acetate
Cyclophosphamide
BB 1101
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Protease Inhibitors