Clinical trial NCT02248428: Clarithromycin Plus CTd Regimen for Patients With Newly Diagnosed Multiple Myeloma
Official title: Clarithromycin Plus CTd (Cyclophosphamide,Thalidomide and Dexamethasone)Regimen for Patients With Newly Diagnosed Multiple Myeloma:a Phase 3 , Multicenter,Randomized, Open-Label Trial.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Multiple Myeloma
Keywords: multiple myeloma
Clarithromycin
CTd
Lead sponsor: Jinling Hospital, China
Sponsor class: OTHER
First posted: 2014-09-25
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Very Good Partial Remission (VGPR) or Better
timeFrame: up to 4 months
Secondary outcomes:
measure: Median Progression Free Survival (PFS) in months
timeFrame: 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
measure: 2 Year Overall Survival (OS) Rate
timeFrame: up to 24 months
measure: Number of participants with adverse events
timeFrame: up to 48 months
Other outcomes:
Locations:
city: Nanjing
country: China
facility: Jinling Hospital
state: Jiangsu
Study officials:
affiliation: Jinling Hospital, China
name: Yongping Zhai, doctor
role: STUDY_CHAIR
References: