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Clarithromycin Plus CTd Regimen for Patients With Newly Diagnosed Multiple Myeloma (CTd)

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ClinicalTrials.gov Identifier: NCT02248428
Recruitment Status : Recruiting
First Posted : September 25, 2014
Last Update Posted : September 6, 2017
Sponsor:
Information provided by (Responsible Party):
Yongping Zhai, Jinling Hospital, China

Tracking Information
First Submitted Date  ICMJE September 22, 2014
First Posted Date  ICMJE September 25, 2014
Last Update Posted Date September 6, 2017
Study Start Date  ICMJE April 2012
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 24, 2014)
Percentage of Participants With Very Good Partial Remission (VGPR) or Better [ Time Frame: up to 4 months ]
Quality of response: % Complete Response (CR) + Very Good Partial Remission (VGPR) to induction BiCTd or CTd as assessed using International Myeloma Working Group Response Definitions. Very Good Partial Remission (VGPR): Detectable serum and urine M component on immunofixation but not on electrophoresis or 90% or greater reduction in serum M protein with less than 100 mg/24 h of urinary M protein. Complete Remission (CR): The presence of less than 5% bone marrow plasmacytosis and the disappearance of all evidence of serum and urine M-components on electrophoresis as well as by immunofixation. In addition, soft tissue plasmacytoma must have disappeared.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02248428 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 24, 2014)
  • Median Progression Free Survival (PFS) in months [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 Months ]
    PFS: Time from study entry to progression/relapse or death from study entry to death of any cause, assessed using International Myeloma Working Group Response Definitions. Progressive Disease (PD): One of the following criteria must be met: a. Increase of 25% or greater in serum M protein (absolute increase greater or equal to 0.5g/dl); b. Increase of 25% or greater in urine M protein (absolute increase greater than 200 mg/24h); c. Increase of 25% or greater in the difference between the involved and uninvolved free light chain (absolute increase greater than 10 mg/dl); d. Increase of 25% or greater in bone marrow plasma cell percentage (absolute percent greater than 5% in case the patient was in CR and 10% otherwise); i.e. Definite development of new bone lesions or soft tissue plasmacytomas, or increase in the size of existing plasmacytomas by greater or equal to 25%. Development of hypercalcemia (serum calcium > 11.5 mg/dl) attributable only to the plasma cell dyscrasia.
  • 2 Year Overall Survival (OS) Rate [ Time Frame: up to 24 months ]
    Percentage of participants with Overall Survival in response to BiCTd or CTd in newly diagnosed multiple myeloma patients with active disease. Overall survival is time from study entry to death of any cause.
  • Number of participants with adverse events [ Time Frame: up to 48 months ]
    Adverse events (AEs) were graded according to NCI-CTCAE Version 4.0
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 Plus CTd Regimen for Patients With Newly Diagnosed Multiple Myeloma
Official Title  ICMJE Clarithromycin Plus CTd (Cyclophosphamide,Thalidomide and Dexamethasone)Regimen for Patients With Newly Diagnosed Multiple Myeloma:a Phase 3 , Multicenter,Randomized, Open-Label Trial.
Brief Summary Due to economic reasons, thalidomide is still widely used as a first line drug for Multiple Myeloma patients in China. However,the efficacy of CTd is still lower than the therapeutic regimens with new drugs. Clarithromycin may have partly efficacy in association with steroids and thalidomide for Multiple Myeloma patients. This multicenter, randomized, phase 3 clinical trial is proposed to explore whether clarithromycin could potentiate responsiveness of CTd (Cyclophosphamide, Thalidomide and Dexamethasone) regimen in Newly Diagnosed Multiple Myeloma patients. The trial will also evaluate the side effects caused by the combination of these drugs.
Detailed Description

This phase III,randomized controlled trial will enroll 130(65 each arm) newly diagnosed patients with active disease from 4 medical centers in East China.

The participants are randomly equally selected to receive BiCTd regimen arm or CTd regimen arm. The treatment consists of eight induction and consolidation therapy followed by maintenance therapy.

BiCTd(Clarithromycin, Cyclophosphamide, Thalidomide and Dexamethasone) regimen arm:

Induction and consolidation Phase:

All patients will also receive aspirin 100mg PO QD while receiving BiCTd. Aspirin will continue through maintenance.

Clarithromycin 500 mg orally daily on days 1-28,thalidomide 100-200mg orally on days d1-28, dexamethasone 40 mg orally on days on 1,8,15,22, and cyclophosphamide 300 mg/m^2 intravenously on day 1-3. Eight Cycles were repeated every 28 days.

If efficacy <PR after 4 cycles of induction, or disease progression at anytime,patients will be quitted.

Maintenance Therapy:

Patients who complete the induction and consolidation regimen could be started on maintenance therapy as follows: Maintenance with CP (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) regimen until disease progression.

CTd regimen arm:

Induction and consolidation Phase:

All patients will also receive aspirin 100mg PO QD while receiving CTd. Aspirin will continue through maintenance.

Thalidomide 100-200mg orally on days d1-28, dexamethasone 40 mg orally on days on 1,8,15,22, and cyclophosphamide 300 mg/m^2 intravenously on day 1-3. Eight Cycles were repeated every 28 days.

If efficacy <PR after 4 cycles of induction, or disease progression at anytime,patients will be quitted.

If no further reduction in the serum and urine M protein in the next cycle,patients may cross over to BiCTd regimen.

Maintenance Therapy:

Patients who complete the induction and consolidation regimen could be started on maintenance therapy as follows: Maintenance with CP (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) regimen until disease progression Then, patients will be followed up for 24 months after chemotherapy. The investigators will record all the laboratory and clinical investigations to assess response at different points of the study. We also assess adverse events (AEs), as graded according to NCI-Common Toxicity Criteria for Adverse Effects (CTCAE) Version 4.0.Response categories were based on the International Myeloma Working Group uniform response criteria.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Multiple Myeloma
Intervention  ICMJE
  • Drug: Clarithromycin
    500mg orally daily on days 1-28,repeated every 28 days
    Other Names:
    • Abbott- 56268
    • Biaxin
    • CLARITH
  • Drug: Thalidomide
    Thalidomide 100-200mg orally per night on days 1-28,repeated every 28 days
    Other Names:
    • Distaval
    • Thalomid
  • Drug: Cyclophosphamide
    300mg/m^2 intravenously daily on day 1-3,repeated every 28 days
    Other Names:
    • Endoxan
    • Cytoxan
    • Neosar
    • Procytox
    • Revimmune
  • Drug: Dexamethasone
    40 mg orally weekly on days 1,8,15,22,repeated every 28 days
    Other Names:
    • Decadron
    • Aeroseb-Dex
    • Decaderm
    • DM
    • DXM
Study Arms  ICMJE
  • Experimental: BiCTd regimen

    Induction and consolidation therapy: BiCTd regimen for 8 cycles. Patients received Clarithromycin 500 mg orally on days 1-28,thalidomide 100-200mg orally on days d1-28, dexamethasone 40mg orally on days on 1,8,15,22, and cyclophosphamide 300mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.

    Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,repeated every 28 days) until disease progression.

    If efficacy <PR after 4 cycles of induction or disease progression at anytime,patients will be quitted.

    Interventions:
    • Drug: Clarithromycin
    • Drug: Thalidomide
    • Drug: Cyclophosphamide
    • Drug: Dexamethasone
  • Active Comparator: CTd regimen

    Induction and consolidation therapy: CTd regimen for 8 cycles. Patients received thalidomide 100-200mg orally on days d1-28, dexamethasone 40 mg orally on days on 1,8,15,22, and cyclophosphamide 300 mg/m^2 intravenously on day 1-3. Cycles were repeated every 28 days.

    Maintenance therapy:CP regimen (cyclophosphamide 200 mg orally on days 1-14 and prednisone 30mg twice daily orally on days 1-7,28 Days per Cycle) until disease progression.

    If efficacy <PR after 4 cycles of induction or disease progression at anytime,patients will be quitted.

    If no further reduction in the serum and urine M protein in the next cycle,patients may cross over to BiCTd regimen.

    Interventions:
    • Drug: Thalidomide
    • Drug: Cyclophosphamide
    • Drug: Dexamethasone
Publications * Not Provided

*   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 Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 24, 2014)
130
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 2020
Estimated Primary Completion Date September 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Signed informed consent form
  • Able to adhere to the study visit schedule and other protocol requirements
  • Diagnosed with active multiple myeloma
  • Previously untreated
  • Karnofsky performance status(KPS) ≥50(KPS<50 will be allowed if related to bony disease)
  • New York Heart Association(NYHA) functional ≤class III

Exclusion Criteria:

  • Hypersensitivity to clarithromycin or any of its excipients, erythromycin, or any of the macrolide antibiotics;
  • Concomitant administration of cisapride, pimozide, astemizole, terfenadine, ergotamine or dihydroergotamine, simvastatin, lovastatin, and atorvastatin;
  • A history of cholestatic jaundice/hepatic dysfunction associated with prior use of clarithromycin.
  • Impaired renal function,Creatinine ≥221umol/L;
  • Pregnant or breast feeding females.
  • Any condition which places the subject at unacceptable risk if he/she were to participate in the study or confounds the ability to interpret data from 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: Yongping Zhai, doctor 13951947646 ypzhai@medmail.com.cn
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02248428
Other Study ID Numbers  ICMJE NAB20140324
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Yongping Zhai, Jinling Hospital, China
Study Sponsor  ICMJE Jinling Hospital, China
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Yongping Zhai, doctor Jinling Hospital, China
PRS Account Jinling Hospital, China
Verification Date September 2017

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