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Clarithromycin in Multiple Myeloma Induction Therapy (CLAIM)

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ClinicalTrials.gov Identifier: NCT02573935
Recruitment Status : Terminated (Suspected side effects to the combination of clarithromycin and VCD (bortezomib, cyclophosphamide and dexamethasone))
First Posted : October 12, 2015
Last Update Posted : September 20, 2016
Sponsor:
Collaborator:
Danish Myeloma Study Group
Information provided by (Responsible Party):
Henrik Gregersen, Aalborg University Hospital

Tracking Information
First Submitted Date  ICMJE October 8, 2015
First Posted Date  ICMJE October 12, 2015
Last Update Posted Date September 20, 2016
Study Start Date  ICMJE January 2015
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 9, 2015)
Comparison of number of participants with very good partial response or better response after three courses of VCD combined with clarithromycin or placebo [ Time Frame: 10 weeks ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02573935 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 9, 2015)
  • Comparison of number of participants with very good partial response or better response after HDT in patients treated with three courses of VCD combined with clarithromycin or placebo [ Time Frame: Five months ]
  • Comparison of number of participants with sCR, CR, PR, PD or SD in the treatment groups after induction therapy and HDT, respectively [ Time Frame: Five months ]
  • Comparison of frequency of infections in patients treated VCD combined with clarithromycin or placebo [ Time Frame: 9 weeks ]
  • Comparison of number of stem cells harvested in patients treated with clarithromycin and placebo in combination with VCD [ Time Frame: Three months ]
  • Neurotoxicity assessed by FACT/GOG-Ntx, Version 4.0 [ Time Frame: Five months ]
  • Quality of life assessed by EORTC QLQ-MY20 [ Time Frame: Five months ]
  • Quality of life assessed by EORTC QLQ-C30 [ Time Frame: Five months ]
  • Comparison of adverse events in patients treated VCD combined with clarithromycin or placebo assessed by CTCAE v4.0 [ Time Frame: Three months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Clarithromycin in Multiple Myeloma Induction Therapy
Official Title  ICMJE A Randomized Placebo-controlled Phase II Study of Clarithromycin or Placebo Combined With VCD Induction Therapy Prior to High-dose Melphalan With Stem Cell Support in Patients With Newly Diagnosed Multiple Myeloma
Brief Summary This study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma.
Detailed Description

The survival in younger myeloma patients improved in the nineties with the introduction of high-dose melphalan with autologous stem cell support (HDT). However, all patients will eventually experience relapse after HDT and there is a need for improvement of the response after HDT. The choice of induction treatment before HDT affects the outcome after induction therapy as well as the outcome after HDT.

Clarithromycin is a macrolide antibiotic frequently utilized in the treatment of respiratory tract infections and is often used in patients with known hypersensitivity to beta-lactam antibiotic. Besides antibiotic activity, clarithromycin may exert immunomodulatory and anti-inflammatory effects. The toxicity profile of clarithromycin is favourable and the cost is very low.

Studies on cell lines have shown that clarithromycin attenuates autophagy in myeloma cells and a recent study has demonstrated that treatment with clarithromycin enhanced bortezomib-induced cytotoxicity in myeloma cells. Phase II studies without control groups have indicated that clarithromycin might enhance the effect of the thalidomide and lenalidomide. A case-matched analysis compared patients at one centre receiving clarithromycin, lenalidomide and dexamethasone with an equal number of patients at another centre receiving lenalidomide and dexamethasone. This study indicated a favourable effect of clarithromycin with a higher frequency of complete response, very-good-partial-response or better response and progression-free survival. However, there is a need for controlled studies to determine whether clarithromycin might enhance the effect of other myeloma agents.

This randomized placebo-controlled study will include 160 patients with newly diagnosed multiple myeloma eligible for HDT. The study evaluates the potential synergic anti-myeloma activity of clarithromycin when combined with VCD induction therapy in patients with newly diagnosed multiple myeloma, and is conducted by the Danish Myeloma Study Group (DMSG) at seven clinics in Denmark. The first patient was included in May 2015 and enrolment is expected to continue until October 2016. The study ends when the last included patient has been followed for two months after HDT.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Clarithromycin
    p.o. clarithromycin 500 mg twice daily for 63 days
  • Drug: Placebo
    Placebo tablet twice daily for 63 days
  • Drug: VCD induction therapy
    Three courses of VCD (sc bortezomib 1.3 mg/sqm days 1, 4, 8, 11, iv cyclophosphamide 500 mg/sqm on days 1 and 8, and p.o. dexamethasone 40 mg days 1, 2, 4, 5, 8, 9, 11, 12 in each 21-days course)
Study Arms  ICMJE
  • Experimental: Clarithromycin
    Clarithromycin combined with VCD induction therapy
    Interventions:
    • Drug: Clarithromycin
    • Drug: VCD induction therapy
  • Placebo Comparator: Placebo
    Placebo combined with VCD induction therapy
    Interventions:
    • Drug: Placebo
    • Drug: VCD induction therapy
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: September 19, 2016)
58
Original Estimated Enrollment  ICMJE
 (submitted: October 9, 2015)
160
Actual Study Completion Date  ICMJE September 2016
Actual Primary Completion Date September 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Myeloma diagnosis according to IMWG criteria
  • Treatment demanding disease
  • High-dose melphalan with stem cell support scheduled as a part of the treatment
  • Signed informed consent given prior to any study related activities
  • Age > 18 years

Exclusion Criteria:

  • Allogeneic transplantation scheduled as a part of the treatment
  • Myeloma treatment prior to entry in the study, except radiotherapy, bisphosphonates/denosumab or corticosteroids for symptom control
  • Concurrent disease making clarithromycin treatment unsuitable
  • Positive pregnancy test (only applicable for women with childbearing potential)
  • Known or suspected hypersensitivity or intolerance to clarithromycin
  • Prolonged QT corrected (QTc) interval ( > 500 msec on screening ECG)
  • Concurrent treatment with cabergoline, fluconazole, ketoconazole, pimozide, quetiapine, sirolimus, verapamil, tacrolimus, ergot alkaloid, simvastatin or other statins
  • Uncontrolled or severe cardiovascular disease including myocardial infarction within 6 months of enrolment, uncontrolled angina or known cardiac amyloidosis
  • Severe renal dysfunction (estimated creatinine clearance <10 mL/min)
  • Serious medical or psychiatric illness which, in the judgment of the investigator, would make the patient inappropriate for entry into the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02573935
Other Study ID Numbers  ICMJE DMSG 03/14
2014-002187-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Henrik Gregersen, Aalborg University Hospital
Study Sponsor  ICMJE Henrik Gregersen
Collaborators  ICMJE Danish Myeloma Study Group
Investigators  ICMJE
Principal Investigator: Henrik Gregersen, MD Aalborg University Hospital
PRS Account Aalborg University Hospital
Verification Date September 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP