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Phase II Study of Thalidomide, Clarithromycin, Lenalidomide, and Dexamethasone for Newly Diagnosed Multiple Myeloma (T-BiRD)

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Celgene
Information provided by (Responsible Party):
Weill Medical College of Cornell University
ClinicalTrials.gov Identifier:
NCT00538733
First received: October 2, 2007
Last updated: June 20, 2017
Last verified: June 2017
  Purpose

Study Objectives

  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. 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. Evaluate the safety of the combination of clarithromycin, lenalidomide, dexamethasone, and thalidomide as a therapy for patients with newly diagnosed MM

Condition Intervention Phase
Multiple Myeloma Drug: thalomid Drug: lenalidomide Drug: clarithromycin Drug: dexamethasone Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: A Phase II Study of Thalidomide (THALOMID®), Clarithromycin (BIAXIN®), Lenalidomide(REVLIMID®), and Dexamethasone (DECADRON®) for Subjects With Newly Diagnosed Multiple Myeloma

Resource links provided by NLM:


Further study details as provided by Weill Medical College of Cornell University:

Primary Outcome Measures:
  • Effect of Drug Combination on Multiple Myeloma [ Time Frame: 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 ]
    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/


Secondary Outcome Measures:
  • Median Time to Maximum Response [ Time Frame: from baseline to cycle with maximum response ]
    Median Time to maximum response, reported in cycles of treatment. One cycle = 28 days.

  • Event Free Survival [ Time Frame: 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 [ Time Frame: From start of treatment, to the date of first progression ]

    Progression determined using International Myeloma Working Group criteria, as defined below.

    An increase of > 25% from lowest response value one or more of the following:

    • Serum M-component and/or (the absolute increase must be > 0.5 g/dL)*
    • Urine M-component and/or (the absolute increase must be > 200 mg/24 h)
    • Only in patients without measurable serum and urine M-protein levels; the difference between involved and uninvolved FLC levels. The absolute increase must be > 10 mg/dL
    • Bone marrow plasma cell percentage; the absolute percentage must be > 10%
    • Definite development of new bone lesions or soft tissue plasmacytomas or definite increase in the size of existing bone lesions or soft tissue plasmacytomas
    • Development of hypercalcaemia (corrected serum calcium > 11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder *if starting serum M protein is greater then 5 g/dL, absolute increase of 1g/dL is sufficient to determine relapse.


Enrollment: 26
Actual Study Start Date: October 2007
Estimated Study Completion Date: December 2019
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: T-BiRD Therapy

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

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)

Drug: lenalidomide

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

Drug: clarithromycin

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)

Drug: dexamethasone

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)


  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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)
    • Serum SGPT/ALT <3.0 x upper limits of normal (ULN)
    • Serum creatinine <2.5 mg/dL (221 µmol/L)
    • Serum total bilirubin <2.0 mg/dL (34 µmol/L)

Exclusion Criteria:

  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00538733

Locations
United States, New York
Weill Medical College of Cornell University
New York, New York, United States, 10021
Sponsors and Collaborators
Weill Medical College of Cornell University
Celgene
Investigators
Principal Investigator: Ruben Niesvizky, MD Weill Medical College of Cornell University
  More Information

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Weill Medical College of Cornell University
ClinicalTrials.gov Identifier: NCT00538733     History of Changes
Other Study ID Numbers: 0707009285
RV-MM-PI-238
Study First Received: October 2, 2007
Results First Received: February 21, 2017
Last Updated: June 20, 2017

Keywords provided by Weill Medical College of Cornell University:
myeloma
newly diagnosed multiple myeloma

Additional relevant MeSH terms:
Multiple Myeloma
Neoplasms, Plasma Cell
Neoplasms by Histologic Type
Neoplasms
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Lymphoproliferative Disorders
Immunoproliferative Disorders
Immune System Diseases
Dexamethasone acetate
Dexamethasone
Dexamethasone 21-phosphate
Lenalidomide
Thalidomide
BB 1101
Clarithromycin
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on June 23, 2017