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Clarithromycin,Lenalidomide and Dexamethasone for Relapsed/Refractory Myeloma

Primary Purpose

Relapse/Refractory Multiple Myeloma

Status

Withdrawn

Phase

Phase 2

Locations

China

Study Type

Interventional

Intervention

clarithromycin

Lenalidomide

Dexamethasone

About this trial

This is an interventional treatment trial for Relapse/Refractory Multiple Myeloma

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patient has a previous diagnosis of multiple myeloma
Patient requires retreatment for multiple myeloma
Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI
Subject has a Karnofsky performance status ≥60% (>50% if due to bony involvement of myeloma (see Appendix IV)
Subject has a life expectancy ≥ 3 months
Subjects must meet the following laboratory parameters:

Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) Hemoglobin ≥ 7 g/dL Platelet count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration) Serum SGOT/AST <3.0 x upper limits of normal (ULN) Serum SGPT/ALT <3.0 x upper limits of normal (ULN) Serum total bilirubin <2.0 mg/dL (34 µmol/L) Creatinine clearance ≥ 30 cc/min

Exclusion Criteria:

Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning)
Subject has a prior history of other malignancies unless disease-free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels
Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure (see Appendix VI), Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities
Female subject who is pregnant or lactating
Subject has known HIV infection
Subject has known active hepatitis B or hepatitis C infection
Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program
Subject is unable to reliably take oral medications
Subject has known hypersensitivity to dexamethasone,cyclophosphamide,paclitaxel
Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment
Subject has any clinically significant medical or psychiatric disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Sites / Locations

Sun Yat-sen University Cancer Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Intervention

Arm Description

All patients received clarithromycin, lenalidomide, and dexamethasone in 28-day cycles. Dexamethasone (40 mg) was given orally on days 1, 8, 15, and 22. Clarithromycin (500 mg) was given orally twice daily.Lenalidomide (25 mg) was given orally daily on days 1 to 21

Outcomes

Primary Outcome Measures

Overall Response Rate (ORR)

ORR is defined as the proportion of patients with CR, nCR or partial response (PR) based on modified EBMT criteria per investigator assessment

Secondary Outcome Measures

Progression Free Survival (PFS)

PFS, defined as time from first dose of study treatment to progression or death due to any cause, as assessed by investigator

Overall survival (OS)

OS, defined as time from first dose of study treatment to death

Safety of combination therapy assessed using the National Cancer institute-Common Toxicology Criteria (NCI-CTC) grade scale for AEs and Lab assessments

Safety of combination therapy (Clarithromycin,lenalidomide and dexamethasone) as assessed by toxicity, which will be assessed using the National Cancer Institute-Common Toxicology Criteria (NCI-CTC) grading scale for Adverse Events and for laboratory assessments (v4.03) that include biochemistry, hematology, urinalysis; special safety assessments that include LVEF, Thyroid function Creatinine clearance and ECGs (electrocardiograms).

Genomic Predictors of Response Rate and PFS

Blood (about 1-2 tablespoons) collected for biomarker and routine tests and to evaluate the ORR and PFS.

Full Information

NCT ID

NCT02986451

First Posted

December 6, 2016

Last Updated

August 11, 2018

Sponsor

Sun Yat-sen University

Collaborators

China Food and Drug Administration

1. Study Identification

Unique Protocol Identification Number

NCT02986451

Brief Title

Clarithromycin,Lenalidomide and Dexamethasone for Relapsed/Refractory Myeloma

Official Title

Efficacy and Safety Study of BiRD (Biaxin [Clarithromycin]/Revlimid [Lenalidomide]/Dexamethasone) Combination Therapy in Relapsed/Refractory Myeloma

Study Type

Interventional

2. Study Status

Record Verification Date

August 2018

Overall Recruitment Status

Withdrawn

Study Start Date

December 2016 (undefined)

Primary Completion Date

December 2018 (Anticipated)

Study Completion Date

December 2019 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Sun Yat-sen University

Collaborators

China Food and Drug Administration

4. Oversight

Data Monitoring Committee

5. Study Description

Brief Summary

This phase II study investigating the efficacy and safety of a combination of biaxin,lenalidomide and dexamethasone in subjects with relapsed/refractory MM.

Detailed Description

The combination of lenalidomide and dexamethasone is effective in increasing the response rate, time to progression, and overall survival in patients with relapsed or refractory myeloma.Clarithromycin is an antibiotic that has shown efficacy in association with steroids and lenalidomide.Clarithromycin, lenalidomide and dexamethasone (BiRd) in newly diagnosed MM has yielded an overall response rates (ORR) of 93% and a progression-free survival (PFS) of 43 months.No prospective study of BiRd to treat relapsed or refractory myeloma has been reported so far.The goal of this phase 2 clinical trial was to assess the response rate and toxicity of a combination regimen of clarithromycin (Biaxin), lenalidomide (Revlimid), and dexamethasone (BiRD) for the treatment of relapsed/refractory MM.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Relapse/Refractory Multiple Myeloma

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

clarithromycin

Other Intervention Name(s)

Biaxin

Intervention Description

Clarithromycin 500mg PO twice daily on days 1-28 for a 28-day cycle.

Intervention Type

Drug

Intervention Name(s)

Lenalidomide

Other Intervention Name(s)

Revlimid

Intervention Description

Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle

Intervention Type

Drug

Intervention Name(s)

Dexamethasone

Other Intervention Name(s)

hexadecadrol

Intervention Description

Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle.

Primary Outcome Measure Information:

Title

Overall Response Rate (ORR)

Description

ORR is defined as the proportion of patients with CR, nCR or partial response (PR) based on modified EBMT criteria per investigator assessment

Time Frame

30 months

Secondary Outcome Measure Information:

Title

Progression Free Survival (PFS)

Description

PFS, defined as time from first dose of study treatment to progression or death due to any cause, as assessed by investigator

Time Frame

30 months

Title

Overall survival (OS)

Description

OS, defined as time from first dose of study treatment to death

Time Frame

30 months

Title

Safety of combination therapy assessed using the National Cancer institute-Common Toxicology Criteria (NCI-CTC) grade scale for AEs and Lab assessments

Description

Time Frame

30 months

Title

Genomic Predictors of Response Rate and PFS

Description

Blood (about 1-2 tablespoons) collected for biomarker and routine tests and to evaluate the ORR and PFS.

Time Frame

30 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Patient has a previous diagnosis of multiple myeloma Patient requires retreatment for multiple myeloma Subject has measurable disease as defined by > 0.5 g/dL serum monoclonal protein, >10 mg/dL involved serum free light chain (either kappa or lambda) provided that the serum free light chain ratio is abnormal, >0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s) of at least 1cm in greatest dimension as measured by either CT scanning or MRI Subject has a Karnofsky performance status ≥60% (>50% if due to bony involvement of myeloma (see Appendix IV) Subject has a life expectancy ≥ 3 months Subjects must meet the following laboratory parameters: Absolute neutrophil count (ANC) ≥750 cells/mm3 (1.0 x 109/L) Hemoglobin ≥ 7 g/dL Platelet count ≥ 75,000/mm3 (30 x 109/L if extensive bone marrow infiltration) Serum SGOT/AST <3.0 x upper limits of normal (ULN) Serum SGPT/ALT <3.0 x upper limits of normal (ULN) Serum total bilirubin <2.0 mg/dL (34 µmol/L) Creatinine clearance ≥ 30 cc/min Exclusion Criteria: Subject has immeasurable MM (no measurable monoclonal protein, free light chains in blood or urine, or measureable plasmacytoma on radiologic scanning) Subject has a prior history of other malignancies unless disease-free for ≥ 5 years, except for basal cell or squamous cell carcinoma of the skin, carcinoma in situ of the cervix or breast, or localized prostate cancer with Gleason score < 7 with stable prostate specific antigen (PSA) levels Subject has had myocardial infarction within 6 months prior to enrollment, or NYHA (New York Hospital Association) Class III or IV heart failure (see Appendix VI), Ejection Fraction < 35%, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities Female subject who is pregnant or lactating Subject has known HIV infection Subject has known active hepatitis B or hepatitis C infection Subject has active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program Subject is unable to reliably take oral medications Subject has known hypersensitivity to dexamethasone,cyclophosphamide,paclitaxel Subject has a history of thromboembolic event within the past 4 weeks prior to enrollment Subject has any clinically significant medical or psychiatric disease or condition that, in the investigator's opinion, may interfere with protocol adherence or a subject's ability to give informed consent

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

zhongjun xia, MD.

Organizational Affiliation

hematological oncology department

Official's Role

Principal Investigator

Facility Information:

Facility Name

Sun Yat-sen University Cancer Center

City

GuangZhou

State/Province

Guangdong

ZIP/Postal Code

510060

Country

China

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Clarithromycin,Lenalidomide and Dexamethasone for Relapsed/Refractory Myeloma

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