Clarithromycin,Lenalidomide and Dexamethasone for Relapsed/Refractory Myeloma

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

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

Study Overview

• Status: Withdrawn
• Conditions: Relapse/Refractory Multiple Myeloma
• Intervention / Treatment: Drug: clarithromycin; Drug: Lenalidomide; Drug: Dexamethasone

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.

• Study Type: Interventional
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Guangdong
    • GuangZhou, Guangdong, China, 510060
      • Sun Yat-sen University Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention; 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	Drug: clarithromycin; Clarithromycin 500mg PO twice daily on days 1-28 for a 28-day cycle.; Other Names: Biaxin; Drug: Lenalidomide; Lenalidomide 25mg PO daily on days 1-21 of a 28-day cycle; Other Names: Revlimid; Drug: Dexamethasone; Dexamethasone 40mg PO will be given on days 1, 8, 15, 22 of a 28-day cycle.; Other Names: hexadecadrol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	30 months
Overall survival (OS)	OS, defined as time from first dose of study treatment to death	30 months
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).	30 months
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.	30 months

Collaborators and Investigators

• Sponsor: Sun Yat-sen University
• Collaborators: China Food and Drug Administration
• Investigators: Principal Investigator: zhongjun xia, MD., hematological oncology department

Study record dates

Study Major Dates

• Study Start: December 1, 2016
• Primary Completion (Anticipated): December 1, 2018
• Study Completion (Anticipated): December 1, 2019

Study Registration Dates

• First Submitted: December 6, 2016
• First Submitted That Met QC Criteria: December 6, 2016
• First Posted (Estimate): December 8, 2016

Study Record Updates

• Last Update Posted (Actual): August 14, 2018
• Last Update Submitted That Met QC Criteria: August 11, 2018
• Last Verified: August 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Immune System Diseases; Neoplasms by Histologic Type; Neoplasms; Lymphoproliferative Disorders; Immunoproliferative Disorders; Hematologic Diseases; Hemorrhagic Disorders; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Multiple Myeloma; Neoplasms, Plasma Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Autonomic Agents; Peripheral Nervous System Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunologic Factors; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Dexamethasone; Lenalidomide; Clarithromycin
• Other Study ID Numbers: MM-2016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO