Phase II Study of Thalidomide, Clarithromycin, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma

NCT00538733 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 0707009285RV-MM-PI-238
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Study Objectives

1. 1.Evaluate the efficacy of the combination of thalidomide (Thalomid®), clarithromycin (Biaxin®), lenalidomide (Revlimid®), and dexamethasone (Decadron®) as an induction therapy for patients with newly diagnosed multiple myeloma (MM).
2. 2.Evaluate the efficacy of the addition of thalidomide (Thalomid®) to BiRD combination therapy as a therapy to increase the complete response rate for patients with newly diagnosed multiple myeloma.
3. 3.Evaluate the safety of the combination of clarithromycin, lenalidomide, dexamethasone, and thalidomide as a therapy for patients with newly diagnosed MM

Conditions

Multiple Myeloma

Keywords

myeloma; newly diagnosed multiple myeloma

Outcome Measures

Primary Outcomes (1)

• Effect of Drug Combination on Multiple Myeloma

  Objective response rate, defined according to the International Myeloma Working Group (IMWG) criteria as greater then or equal to a Partial Response (PR). The best response was recorded. The IMWG criteria can be found here: imwg.myeloma.org/international-myeloma-working-group-imwg-uniform-response-criteria-for-multiple-myeloma/

  This was collected from patients for their duration on study treatment. Only the best response was recorded. Best responses were reported at any point of the study, from start of treatment up until removal of study, which occurred up to 57.4 cycles

Secondary Outcomes (3)

• Median Time to Maximum Response

  from baseline to cycle with maximum response

• Event Free Survival

  from baseline to the time of first event that lead to removal from study (defined as progression, death, withdrawal of consent, or removal for toxicity)

• Progression Free Survival

  From start of treatment, to the date of first progression

Study Arms (1)

T-BiRD Therapy

EXPERIMENTAL

All patients were treated with the same regimen, starting with T-BIRD therapy (Cycles 1-4). After 4 cycles, Patients with disease progression will be taken off study. Patients who achieve maximum response will receive maintenance. Patients who achieve VGPR or PR will be given T-BiRD for 2 cycles (cycles 5-6). After 6 cycles of T-BiRD, Patients who achieve maximum response will receive maintenance; those with disease progression will be taken off study; all other patients will receive BIRD. Patients who progress on BiRD will reinitiate T-BiRD. If disease progression continues after 2 cycles, patients will be taken off study. Patients in CR/sCR or that achieve a plateau of disease for \> 2 cycles on BiRD or T-BiRD therapy will receive maintenance.

Drug: thalomid; Drug: lenalidomide; Drug: clarithromycin; Drug: dexamethasone

Interventions

thalomid DRUG

Cycles 1-4 • Thalidomide (50mg daily for days 1-7, thereafter 100mg daily for days 8-28 of the first 28 day cycle. Thalidomide will then be given at 100mg/daily for days 1-28 for each subsequent cycle)

T-BiRD Therapy

lenalidomide DRUG

During T-BIRD Phase (Cycles 1-4, 5-6, and in the case of T-BIRD re-initiation) • Lenalidomide (25 mg daily days 1-21 of every 28 day cycle) During BiRD phase • 25mg daily days 1-21 of every 28 day cycle) During Maintenance Phase • 25 mg daily for days 1-21 out of a 28 day cycle

T-BiRD Therapy

clarithromycin DRUG

During T-BiRD Phase • Clarithromycin (500mg twice daily for each 28 day cycle) During BiRD Phase: • Clarithromycin (500mg twice daily for each 28 day cycle)

T-BiRD Therapy

dexamethasone DRUG

During T-BIRD Phase (Cycles 1-4, 5-6, and in the case of T-BIRD re-initiation) • Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle) During BiRD Phase: • Dexamethasone (40 mg daily on day 1, 8, 15 and 22 of each 28 day cycle) During Maintenance Phase • Dexamethasone 20 mg weekly (days 1,8, 15, 22 out of a 28 day cycle)

T-BiRD Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject must voluntarily sign and understand written informed consent.
• Age \> 18 years at the time of signing the consent form.
• Histologically confirmed Salmon-Durie stage II or III MM. Stage I MM patients will be eligible if they display poor prognostic factors (ß2M ≥5.5 mg/L, plasma cell proliferation index ≥5%, albumin of less then 3.0, and unfavorable cytogenetics).
• Newly diagnosed myeloma.
• No anti-myeloma 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 be receiving adjuvant antiresorptive therapy (i.e., pamidronate or zoledronic acid) as routine care.
• Measurable disease as defined by \> 1.0 g/dL serum monoclonal protein, \>0.1 g/dL serum free light chains, \>0.2 g/24 hrs urinary M-protein excretion, and/or measurable plasmacytoma(s).
• Karnofsky performance status ≥70% (\>60% if due to bony involvement of myeloma.
• Able to take aspirin daily as prophylactic anticoagulation. (patients intolerant to ASA may use warfarin or low molecular weight heparin)
• All study participants must be registered into the mandatory RevAssist® and S.T.E.P.S.® programs, and be willing and able to comply with the requirements of RevAssist® and the S.T.E.P.S.® programs.
• Females of childbearing potential (FCBP)† must have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 10 - 14 days prior to and again within 24 hours of prescribing lenalidomide and thalidomide (prescriptions must be filled within 7 days) and must either commit to continued abstinence from heterosexual intercourse or begin TWO acceptable methods of birth control, one highly effective method and one additional effective method AT THE SAME TIME, at least 4 weeks before she starts taking lenalidomide. FCBP must also agree to ongoing pregnancy testing. Men must agree to use a latex condom during sexual contact with females of child bearing potential even if they have had a successful vasectomy.
• Life expectancy ≥ 3 months
• Subjects must meet the following laboratory parameters:
• Absolute neutrophil count (ANC) ≥1000 cells/mm3 (1.0 x 109/L)
• Platelets count ≥ 75,000/mm3 (75 x 109/L)
• Serum SGOT/AST \<3.0 x upper limits of normal (ULN)

You may not qualify if:

• Patients with non-secretory MM (no measurable monoclonal protein, free light chains, and/or M-spike in blood or urine).
• Prior history of other malignancies (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or breast) unless disease free for ≥ 5 years.
• Myocardial infarction within 6 months prior to enrollment , or NYHA(New York Hospital Association) Class III or IV heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, electrocardiographic evidence of acute ischemia or active conduction system abnormalities.
• Pregnant or lactating females are ineligible.
• Given the potential of the study drugs to trigger or worsen HIV viremia and the incidence of opportunistic infections inpatients infected with the HIV virus, HIV-1 or HIV-2 positive patients will be excluded. The interactions of HAART with study drugs have not been determined.
• Active hepatitis B or hepatitis C infection.
• Active viral or bacterial infections or any coexisting medical problem that would significantly increase the risks of this treatment program.
• Any coexisting medical problem or laboratory evaluation that, in the treating physician's or principal investigator's opinion, makes the patient unsuitable to participate in this clinical trial.
• Known hypersensitivity to dexamethasone, clarithromycin, lenalidomide, or thalidomide.
• History of thromboembolic event within the past 6 months prior to enrollment.

Sponsors & Collaborators

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

Study Sites (1)

Weill Medical College of Cornell University

New York, New York, 10021, United States

Location

Related Publications (1)

• Mark TM, Bowman IA, Rossi AC, Shah M, Rodriguez M, Quinn R, Pearse RN, Zafar F, Pekle K, Jayabalan D, Ely S, Coleman M, Chen-Kiang S, Niesvizky R. Thalidomide, clarithromycin, lenalidomide and dexamethasone therapy in newly diagnosed, symptomatic multiple myeloma. Leuk Lymphoma. 2014 Dec;55(12):2842-9. doi: 10.3109/10428194.2014.896005. Epub 2014 Mar 25.

  PMID: 24576165 DERIVED

MeSH Terms

Conditions

Multiple Myeloma; Neoplasms, Plasma Cell

Interventions

Thalidomide; Lenalidomide; Clarithromycin; Dexamethasone

Condition Hierarchy (Ancestors)

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)

Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Erythromycin; Macrolides; Polyketides; Lactones; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated

Results Point of Contact

• Title: Jennifer Hess
• Organization: Weill Cornell Medical College

jmh2004@med.cornell.edu

6469629440

Study Officials

• Ruben Niesvizky, MD

  Weill Medical College of Cornell University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 2, 2007
• First Posted: October 3, 2007
• Study Start: October 1, 2007
• Primary Completion: July 1, 2010
• Study Completion: September 17, 2020
• Last Updated: May 24, 2021
• Results First Posted: June 23, 2017

Record last verified: 2021-04

Locations

US (1)