BiRd vs. Rd as Initial Therapy in Multiple Myeloma

NCT02516696 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: 1411015662RV-CL-MM-PI-004078
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

This is a randomized, open-label, phase III study to investigate the efficacy of combination therapy with an induction phase utilizing a combination clarithromycin (Biaxin®), lenalidomide (Revlimid®), dexamethasone (Decadron®), in multiple myeloma patients who are newly diagnosed and require treatment when compared to patients who receive lenalidomide and dexamethasone alone.

Conditions

Multiple Myeloma

Outcome Measures

Primary Outcomes (1)

• Survival Duration Without Disease Progression

  Calculate rate of progression-free survival for subjects following treatment BiRd regimen compared to Rd treatment regimen. Progression is determined by the International Myeloma Working Group Criteria.

  Until disease progression or death from any cause, for a maximum of approximately 5 years

Secondary Outcomes (10)

• Overall Response Rate

  2 years

• Number of Adverse Events Experienced

  2 years

• Overall Survival

  4 years

• Number of Days After Initiating Treatment With BiRd Regimen to Disease Progression, as Compared to Subjects on Rd Treatment Regimen.

  Until disease progression for a maximum of approximately 5 years

• Number of Patients With Objective Response Rate (CR+PR)

  up to 3 years

Study Arms (2)

BiRD treatment regimen

EXPERIMENTAL

Subjects on the BiRD arm will receive clarithromycin, lenalidomide, and dexamethasone in 28-day cycles.

Drug: Clarithromycin; Drug: Lenalidomide; Drug: Dexamethasone

Rd treatment regimen

ACTIVE COMPARATOR

Subjects on the Rd arm will receive lenalidomide and dexamethasone in 28-day cycles.

Drug: Lenalidomide; Drug: Dexamethasone

Interventions

Clarithromycin DRUG

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

Also known as: biaxin

BiRD treatment regimen

Lenalidomide DRUG

25 mg PO days 1-21 followed by a 7 day rest period for each 28-day cycle

Also known as: Revlimid

BiRD treatment regimen; Rd treatment regimen

Dexamethasone DRUG

20 mg PO on Days 1, 8, 15, and 22 for each cycle for subjects 75 years and younger.

Also known as: Decadron

BiRD treatment regimen; Rd treatment regimen

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Subject must voluntarily sign and understand written informed consent.
• Subject is at least 65 years old at the time of signing the consent form.
• Subject has histologically confirmed multiple myeloma that has never before been treated
• Subject has no prior anti-myeloma treatment therapy within 14 days prior to initiation of study treatment except for corticosteroids with a maximum allowed dosage equivalent to three pulses of dexamethasone (40mg daily for 4 days equals one pulse). Patients may have received prior adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care, or radiation therapy as palliation for pain and/or spinal cord compression.
• 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 is able to take prophylactic anticoagulation as detailed in section 9.1 (patients intolerant to aspirin may use warfarin or low molecular weight heparin).
• Subject is registered into the mandatory RevAssist® program, and is willing and able to comply with the requirements of RevAssist® program.
• If subject is a female of childbearing potential (FCBP),† she must have a negative serum or urine pregnancy test with a sensitivity of at least 25 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide
• 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 ≥ 30,000/mm3 (75 x 109/L)
• Serum SGOT/AST \<3.0 x upper limits of normal (ULN)

You may not qualify if:

• 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, clarithromycin, lenalidomide, or thalidomide
• 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.
• Subject has previously been treated for multiple myeloma

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• Celgene Corporation: collaborator

Study Sites (2)

University of Colorado - Anschutz Cancer Center

Aurora, Colorado, 80045, United States

Location

Weill Cornell Medical College

New York, New York, 10065, United States

Location

MeSH Terms

Conditions

Multiple Myeloma

Interventions

Clarithromycin; Lenalidomide; Dexamethasone; Calcium Dobesilate

Condition Hierarchy (Ancestors)

Neoplasms, Plasma Cell; Neoplasms by Histologic Type; Neoplasms; Hemostatic Disorders; Vascular Diseases; Cardiovascular Diseases; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemorrhagic Disorders; Lymphoproliferative Disorders; Immunoproliferative Disorders; Immune System Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Benzenesulfonates; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Arylsulfonates; Arylsulfonic Acids; Sulfonic Acids; Sulfur Acids; Sulfur Compounds

Limitations and Caveats

The significance of these results is limited by the study's low accrual. The study's low accrual was due in part to the COVID-19 pandemic.

Results Point of Contact

• Title: Multiple Myeloma Program Manager
• Organization: Weill Cornell Medicine

hyk4001@med.cornell.edu

646.962.9376

Study Officials

• Jorge Monge, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 4, 2015
• First Posted: August 6, 2015
• Study Start: February 1, 2016
• Primary Completion: June 22, 2022
• Study Completion: July 22, 2022
• Last Updated: June 5, 2023
• Results First Posted: June 5, 2023

Record last verified: 2023-06

Locations

US (2)